Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. …

Small and Large Animal Dermatology

Endocrine Skin Diseases

Endocrine Alopecias - Small Animal

A General Considerations:

1 Endocrine alopecias are usually characterized by bilaterally
symmetrical hair loss

2 The onset is gradual and the progression is slow

3 The head and distal extremities are usually spared

4 Endocrine alopecias are usually non pruritic secondary seborrhea
and/or pyoderma may result in pruritus and/or asymetric alopecic
lesions

5 The hair epilates easily most hair follicles are in the telogen
resting stage

6 The hair coat is usually dull and dry

7 Hair may fail to grow after clipping

8 Comedones black heads are often present

9 Although there are differences, most of them share common clinical
and histologic changes
Endocrine Skin Diseases
Hyperadrenocorticism - Canine

A General Considerations:

1 Hyperadrenocorticism or Cushings disease is the second most common

endocrinopathy in the dog

2 The syndrome is caused by persistently high concentrations of
cortisol in circulating blood

3 Cushings disease can be spontaneous or iatrogenic

4 The spontaneous Cushings is classified in pituitary dependent or
adrenal tumors

5 Spontaneous Cushings is a common disorder of dogs over 6 years of
age and, over 75 of dogs with spontaneous Cushings are older than
9 years

6 Iatrogenic Cushings may occur in dogs of any age or breed, and it
is caused by prolonged oral, topical, or parenteral administration
of exogenous glucocorticoids

7 Many nonadrenal diseases cause clinical signs similar to those seen
in dogs with Cushings syndrome such as renal failure, diabetes
mellitus, liver disease, pyelonephritis, hypothyroidism, diabetes
insipidus, and side effects of anticonvulsant drugs

8 Therefore, a complete evaluation of the patient for nonadrenal
diseases is required before a diagnosis of hyperadrenocorticism is
made

Important Facts

|Cushings disease can be spontaneous or iatrogenic
|
|The spontaneous form is classified in pituitary dependent or adrenal|
|tumor and it is usually seen in dogs older than 6 years of age |
|The iatrogenic form is caused by excessive and/or prolonged |
|administration of exogenous glucocorticoids and it can occur at any |
|age |
|Many nonadrenal diseases cause clinical signs, which mimic |
|Cushings Therefore, a complete evaluation of the patient for |
|nonadrenal diseases is required before a diagnosis of Cushings is |
|made |

B Pathogenesis:

1 Pituitary dependent Cushings PDC accounts for 80 to 85 of the
spontaneous cases

2 The cause of PDC is either a functional tumor microadenoma most
common or macroadenoma or a defect in the hypothalamic-pituitary
axis A functional tumor is the most common cause of PDC

3 In either case, the pituitary will secret excessive amounts of
adrenocorticotrophic hormone ACTH which results in bilateral
adrenocortical hyperplasia with excessive production of cortisol

4 Functional adrenocortical
tumors AT account for about 15 to 20 of
the spontaneous cases

5 They may be adenocarcinomas or adenomas and can occur in either
gland In most cases the tumor is unilateral

6 The contralateral adrenal gland is atrophied as a result of the
negative feedback suppression of ACTH caused by the excessive
cortisol production by the tumor

7 Iatrogenic Cushings caused by glucocorticoid treatment represents
more than half of the cases

Important Facts

|PDC accounts for 80 to 85 of the spontaneous cases |
|PDC is caused by a functional pituitary tumor in most cases |
|However, in some cases the pituitary negative feedback mechanism is |
|not functioning properly |
|In either case, the final result will be excessive production of |
|ACTH by the pituitary gland, which will induce bilateral hyperplasia|
|of the adrenal cortexes resulting in large production of cortisol |
| |
|ATs account for 15 to 20 of the spontaneous cases, and it is |
|usually caused by an unilateral
adenoma or adenocarcinoma |
|The contralateral gland is atrophied due to feedback suppression of |
|ACTH caused by excessive cortisol production by the tumor |
|Iatrogenic Cushings accounts for more than half of the cases |

C Clinical Signs:

1 Signalment:

a Spontaneous Cushings is most commonly seen in middle to older
dogs range 1-18 yrs, mean 10-11 yrs

b No sex predilection

c Most commonly seen in Poodles, Dachshunds, Beagles, Boxers, Boston
Terriers and German Shepherds

2 Common historical findings:

a Polyuria: cortisol-mediated interference with the secretion and/or
action of antidiuretic hormone

b Polydipsia: secondary to the polyuria

c Polyphagia: believed to be a direct effect of glucocorticoids in
the dog

d Lethargy or weakness muscle weakness

e Painting

f Weight gain

g Dermatologic abnormalities

3 Physical findings:

a Pendulous abdomen potbelly: occurs in 90-95 of the cases
Many factors contribute to this common sign:

1 Abdominal fat accumulation

2 Hepatomegaly

3 Urinary bladder distention

4 Muscle wastage profound catabolic effects of
glucocorticoids

b Muscle weakness and atrophy may be attributed to the catabolic
effects of steroids on proteins

c Ocular disorders:

1 Blindness may occur secondary to hypertension and retinal
detachment

2 Large pituitary tumors may cause blindness but usually also
cause concurrent neurologic signs such as somnolence,
disorientation, ataxia and seizures

d Respiratory signs:

1 Panting The panting or increased respiratory rate arises
from a combination of decreased thoracic volume resulting from
redistribution of fat over the thorax, pressure resulting from
the abdominal distention, and weakness of the muscles of
respiration

2 Pulmonary thromboembolism, a more serious complication of
Cushings, may produce acute, severe dyspnea

e Dermatologic signs:

1 Alopecia: usually in a bilateral and symmetrical pattern

2 Thin, hypotonic skin

3 Prominent abdominal
vasculature

4 Stria due to decreased skin elasticity

5 Hyperpigmentation

6 Easy bruising due to fragility of blood vessels

7 Poor wound healing

8 Calcinosis cutis occurs in about 40 of the cases It
usually involves dorsal midline of neck, ventral abdomen and/or
inguinal area

9 Recurrent superficial pyoderma with large bullous pustules

10 Adult onset demodicosis and dermatomycosis rarely occur

11 Seborrhea sicca clinically manifested as smooth fine scales

Important Facts

|The 5 Ps: Polyuria, Polydipsia, Polyphagia, Panting and Potbelly are|
|very common clinical signs |
| |
|Lethargy and exercise intolerance are common complaints, and are |
|usually associated with the muscle wastage caused by the catabolic |
|effect of glucocorticoids on proteins |
| |
|Common dermatologic signs are symmetrical alopecia, thin skin with
|
|smooth scales, poor wound healing, prominent abdominal vasculature, |
|easily bruised skin, dystrophic calcinosis cutis, recurrent |
|superficial pyoderma |

D Diagnosis:

1 History

2 Clinical signs Remember, some nonadrenal disorders cause clinical
signs similar to those seen in dogs with Cushings

3 Minimal database must be acquired to determine the presence of
nonadrenal disorders and to determine the nature and extent of
clinicopathologic abnormalities that exist in the patient The
minimum data base should include:

a CBC

b Serum chemistry profile

c Urinalysis

d Urine culture

4 Clinicopathologic abnormalities associated with Cushings:

a Stress leukograma: neutrophilia, monocytosis, lymphopenia, and
eosinopenia

b Increased alkaline phosphatase, which is induced by
glucocorticoids

c Alanine aminotransferase can also be elevated due to
hepatocellular leakage associated with cell swelling

d Mild hyperglycemia may result from increased gluconeogenesis and
insulin
antagonism by glucocorticoids

e Hypercholesterolemia and lipemia are believed to be a result of
lipolysis

f Usually urine specific gravity is low dilute urine

g Glycosuria and diabetes mellitus occur in about 10 of the cases

h Mild proteinuria occur in 44 to 75 of dogs with Cushings and
should be quantitated with a urine protein: creatinine ratio

5 Hypothalamic-pituitary-adrenal function testing

6 Specific diagnostic tests of hypothalamic-pituitary-adrenal axis:

a Urine cortisol / creatinine ratio:

1 It is a very sensitive test for detection of increased urinary
cortisol excretion

2 Unfortunately, the test is not specific for diagnosis of
Cushings Seventy-five to 80 of dogs with nonadrenal
diseases have increased urine cortisol: creatinine ratio

3 It has a close to 100 negative predictive value; that is, the
likelihood that the test correctly predicts that a dog does
not have Cushings is close to 100

b ACTH stimulation test:

1 The ACTH stimulation test is designed to evaluate the capacity

of the adrenal gland to secrete cortisol after maximal
stimulation

2 It is the best test to determine iatrogenic Cushings It is
also used to diagnose spontaneous Cushings In addition,
this test is needed as a baseline before treating a case with
o,p -DDD Lysodren

3 The ACTH stimulation test may be abnormal in dogs with non-
adrenal illness

4 Normal dogs show increased cortisol levels after ACTH
administration but not too much Baseline cortisol ranges
from 15 to 60 ng/ml in normal dogs; the post-ACTH cortisol
level incremental changes vary from 80 to 160 ng/ml in normal
dogs

5 Iatrogenic Cushings show minimal or no increase in cortisol
levels after ACTH administration

6 Spontaneous Cushings cases show markedly increased post-ACTH
cortisol levels 200 ng/ml response to ACTH compared to
normal dogs but may be variable may see even a normal
response

7 The ACTH stimulation test can diagnose PDC in about 85 of the
cases and AT in
only 50 to 60 of the dogs

8 The test does not differentiate dogs with PDC from those with
AT

9 More than one protocol have been described for the ACTH test:

a One protocol involves measuring plasma cortisol before and
one hour after IM injection of 025 mg/kg of synthetic
corticotrophin ACTH

b An alternative protocol measures plasma cortisol levels
before and 2 hours after IM injection of 22 IU/kg of
porcine aqueous gelatin corticotrophin

Important Facts

|The ACTH stimulation test is a quick and moderately reliable test |
|for Cushings |
| |
|It is the best test to differentiate iatrogenic Cushings from |
|spontaneous Cushings |
| |
|The ACTH stimulation test can diagnose PDC in about 85 of the cases|
|and AT in only 50 to 60 of the dogs |
|
|
|False-positive results can also occur |
| |
|A diagnosis of Cushings should not be confirmed or excluded based |
|on the ACTH test results |
| |
|The test should be interpreted in the context of the history, |
|physical findings, and data base results |
| |
|The test does not differentiate dogs with PDC from those with AT |

c Low dose dexamethasone suppression test LDDST:

1 It is a good screening test for spontaneous Cushings but it
may be abnormal in dogs with non-adrenal illness false
positive results

2 In normal dogs cortisol levels are suppressed to 14 ng/ml at
8 hours

3 In approximately 95 of dogs with PDC and 100 of dogs with AT,
cortisol levels at 8 hours does not suppress below 14 ng/ml
However, in about 5 of dogs
with PDC, the plasma cortisol
suppresses normally

4 Protocol:

a Either 001 mg/kg or 0015 mg/kg of dexamethasone sodium
phosphate or dexamethasone in polyethylene glycol is
administered intravenously after a blood sample has been
obtained for determination of baseline plasma cortisol
levels Samples are collected again at 4 and 8 hours after
administration of dexamethasone

b The 4-hour post-dexamethasone blood sample is used to help
differentiate between PDC and AT

5 This test can differentiate PDC from AT

6 In approximately 40 of the PDC cases the 4-hour post-
dexamethasone sample suppresses the plasma cortisol levels to
any of the following values: 1 less than the value set by the
laboratory at 4 hours, 2 less than 50 of the baseline value
at 4 hours, or 3 less than 50 of the value at 8 hours

7 If no significant suppression is observed at 4 and 8 hours,
this test will not be able to differentiate between PDC and AT
it occurs in 60
of the cases

Important Facts

|LDDST diagnoses PDC Cushings in about 95 of the time and AT in 100|
|of the time |
| |
|If a dog has either PDC or AT, the 8-hour post-dexamethasone |
|cortisol levels should not decrease more than 14 ng/ml |
| |
|LDDST can distinguish PDC from AT in about 40 of the cases |
| |
|If the 4-hour post-dexamethasone cortisol levels show less than 50 |
|of the value at 8 hours, it indicates a case of PDC |
|However, if no suppression occurs at 4 hours, the case can be either|
|PDC or AT no differentiation can be made |

d High dose dexamethasone suppression test:

1 This test is used to differentiate between PDC and AT

2 ACTH hormone production by pituitary tumors is suppressed by
negative feedback if a large enough dose of dexamethasone is
used, and, as
a result, plasma cortisol level is also
suppressed

3 The high dose of dexamethasone does not suppress the pituitary
ACTH secretion, and consequently the plasma cortisol levels if
the dog has an AT remember, the adrenal tumor secretes
cortisol independently of the pituitary gland

4 If a dog has PDC, the 8-hour plasma cortisol level shows more
than 50 decrease of baseline values However, lack of
suppression may occur in as many as 15 to 25 of dogs with
PDC, necessitating use of another discrimination test

5 Protocol:

a Intravenous administration of 01 mg/kg of dexamethasone
sodium phosphate or dexamethasone in polyethylene glycol is
recommended

b Blood samples for measurement of plasma cortisol levels are
collected before and 8 hours after dexamethasone
administration

Important Facts

|HDDST is used to differentiate between PDC and AT |
| |
|It fails to
differentiate PDC from AT in 15 to 25 of the time |
| |
|If a dog has PDC pituitary tumor, the high dose of dexamethasone |
|will suppress the pituitary ACTH and consequently the plasma |
|cortisol levels to a value less than 50 of the baseline value |
| |
|If a dog has an AT, the 8-hour post-dexamethasone cortisol |
|concentration will not suppress more than 50 of the pre or baseline|
|value |

e Endogenous ACTH:

1 This test, like the HDDST, is used to differentiate between
the PDC and AT

2 In dogs with ATs, ACTH secretion is suppressed

3 Excessive ACTH secretion is associated with PDH

4 The normal reference range for endogenous ACTH is about 20 to
100 pg/ml

5 Cushingoid dogs with concentrations of less than 20 ng/ml
typically have ATs or iatrogenic Cushings

6 Dogs with Cushings and endogenous ACTH levels greater than 40
pg/ml typically
have PDC

7 An endogenous ACTH concentration of 20 to 40 pg/ml is
considered to be nondiagnostic

8 Blood samples must be handled quickly because the half-life is
only 25 minutes in whole blood

9 The blood should be collected in chilled plastic tubes because
ACTH adheres to glass

10 The tubes should be immediately centrifuged and frozen at -40C
-40F for transport to the laboratory in frozen condition

Important Facts

|Endogenous ACTH concentration is used to differentiate PDC from AT |
| |
| |
|An endogenous ACTH value less than 20 pg/ml is diagnostic of AT or |
|iatrogenic Cushings |
| |
|An endogenous ACTH concentration higher than 40 pg/ml is diagnostic |
|of PDC |
| |
|An endogenous
ACTH value between 20 and 40 pg/ml is non-diagnostic |
|and requires another discrimination test such as HDDST |

f Abdominal radiography, ultrasonography, and computed tomography:

1 Abdominal radiography:

a In one report, 56 of 23 dogs with AT had radiographic
evidence of adrenal calcification

b Because adrenal calcification is rare in normal dogs and
dogs with PDC, its presence in a dog with Cushings strongly
suggests AT

2 Abdominal ultrasonography:

a In approximately 50 to 70 of dogs with ATs, the tumor is
large enough to be visualized by a trained ultrasonographer

b The hyperplastic adrenal gland can not be visualized, even
by the most experienced ultrasonographer, in a dog with PDC

3 Computed tomography:

a Although the computed tomography may provide diagnostic and
discriminatory information, the expense and practicality of
this technique limit its availability primarily to academic
institutions

Important Facts

|Abdominal radiography can show calcification of the adrenal gland in|
|cases of ATs |
| |
|Because adrenal calcification is rare in normal dogs and dogs wit |
|PDC, its presence in a dog with Cushings strongly suggests AT |
| |
|Abdominal ultrasonography may provide information that helps |
|distinguish PDC from AT |
| |
|In about 50 to 70 of dogs with ATs, the tumor is large enough to |
|be visualized by a trained ultrasonographer |
| |
|The hyperplastic adrenal gland can not be visualized, even by the |
|most experienced ultrasonographer, in a dog with PDC |

E Treatment:

1 Pituitary dependent Cushings PDC:

a Lysodren o,p-DDD:

1 It effectively reduces cortisol secretion by causing a
selective necrosis and
atrophy of the zona fasciculata and
zona reticularis of the adrenal cortex

2 The zona glomerulosa mineralocorticoid production is
relatively resistant So, mineralocorticoid deficiency
associated with hyperkalemia and hyponatremia are uncommon

3 Because Lysodren does not effect a cure, dogs require weekly
lifelong therapy

4 Lysodren therapy is divided into 2 phases: the induction and
the maintenance

5 Induction phase:

a The induction phase consists of loading Lysodren, with the
objective of returning the dogs levels of cortisol to the
normal range

b General recommendation: 40 to 50 mg/kg q24h PO for 7 to 10
days

c Send owners home with prednisone If the dog shows signs of
cortisol deficiency lethargy, depression, weakness,
vomiting, diarrhea, instruct the client to supplement the
dog with oral prednisolone at the dose of 02 to 04 mg/kg q
24, and to contact the veterinarian If no improvement is
noted
after 1 to 3 hours, the animal has to be examined
immediately and, a chemistry profile should be performed to
rule out mineralocorticoid deficiency hyperkalemia and
hyponatremia Lysodren therapy should be discontinued and,
an ACTH stimulation test performed to assess the degree of
adrenal cortex atrophy

d If no signs of signs of mineralocorticoid or glucocorticoid
deficiency are noted, the ACTH stimulation should be
performed in 7 to 10 days to assess the response to Lysodren
therapy

e If the post-ACTH cortisol levels are within or slightly
below the normal range such as, 20 to 40 ng/dl, a
maintenance dosage of Lysodren may be started

f If glucocorticoids are given at any time during Lysodren
therapy, be sure to stop glucocorticoid administration for
48 hrs before having an ACTH stimulation test performed

6 Maintenance phase:

a A maintenance dosage of Lysodren involves giving 50 mg/kg q7
days in 2 to 3
divided dosages

b Lower dosages may result in an increased incidence of
relapse

c Glucocorticoid supplementation generally is not necessary

d An ACTH stimulation test should be repeated after 1 to 2
months of maintenance therapy, and every 6 months
thereafter

e If cortisol levels rise above the normal range, an induction
or loading phase should be reinstituted, and an ACTH
stimulation test should be performed in 7 to 10 days

f The weekly maintenance dosage should be increased by 50

g Approximately half the dogs treated with Lysodren relapse
within 12 months

Important Facts

|Lysodren o,p-DDD will cause necrosis and/or atrophy of the |
|adrenal cortex resulting in the reduction of cortisol secretion |
| |
|It rarely destroys the zona glomerulosa, so mineralocorticoid |
|deficiency hyperkalemia and hyponatremia rarely occurs |
|
|
|The induction phase consists in giving Lysodren daily for about 7 to|
|10 days |
| |
|The maintenance phase consists in giving Lysodren weekly |
| |
|An ACTH stimulation test should always be performed before starting |
|the maintenance phase to assess the response to the daily Lysodren |
|administration |
| |
|An ACTH stimulation test should be performed after 1 to 2 months of |
|the maintenance therapy and, every 6 months thereafter |
| |
|Stop glucocorticoid therapy 48 hours before having an ACTH |
|stimulation test performed |
| |
|Side effects associated with Lysodren therapy include lethargy, |
|vomiting, diarrhea, weakness, anorexia, and ataxia
|

b Ketoconazole:

1 It is an antifungal medication, but it also decreases cortisol
levels

2 It interferes with adrenal steroid synthesis by blocking
enzymes in the cortisol synthetic pathway

3 It is expensive in large-breed dogs up to 6 times more than
Lysodren per month

4 The initial dosage is 10 mg/kg q24h, divided and given twice
daily for 7 to 10 days

5 Treatment success is monitored with an ACTH stimulation test
after 7 to 10 days

6 It is not necessary to discontinue ketoconazole before
testing

7 The dosage may need to be increased to achieve successful
therapy

8 Failure to respond to dosages as high as 30 mg/kg q24h occurs
in up to 20 of cases

9 Reported side effects include anorexia, vomiting, and a
lightening of the hair coat Increase in liver enzymes can
also occur

10 Lifelong therapy, twice daily, must be used to be effective,
because the drug blocks adrenal steroid synthesis without

destroying adrenal tissue

Important Facts

|Ketoconazole interferes with adrenal steroid synthesis by blocking |
|enzymes in the cortisol synthetic pathway, therefore lowering serum |
|cortisol concentrations |
| |
|Drawbacks of ketoconazole therapy include high cost, twice daily |
|administration, and lack of effectiveness in at least half of dogs |
| |
| |
|Potential side effects include anorexia, vomiting, lightening of the|
|hair coat and, increase in liver enzymes |

c L-deprenyl:

1 An increasing body of evidence points to hypothalamic dopamine
deficiency playing a role in the pathogenesis of PDH in the
dog

2 L-deprenyl helps restore depleted central dopamine levels and
facilitates dopaminergic transmission by several mechanisms,
especially potent selective irreversible inhibition of

monoamine oxidase B

3 L-deprenyl also increases the synthesis and release of
dopamine into the synapse, and inhibits dopamine reuptake

4 L-deprenyl is indicated for the treatment of uncomplicated
cases of canine PDC

5 L-deprenyl is not indicated for treatment of dogs with
iatrogenic disease or functional ATs

6 Endocrine function testing to confirm PDC should be performed
before starting therapy

7 The initial dosage is 1 mg/kg per day given orally for at
least 2 months

8 During the first 2 months of therapy, the patient should be
evaluated periodically for clinical response by history and
physical examination

9 As l-deprenyl is not adrenolytic or an inhibitor of adrenal
steroidogenesis, an ACTH-stimulation testing is not necessary

10 If no improvement in clinical signs is evident after 2 months,
the dosage can be increased to a maximum of 2 mg/kg per day
and, the dog reevaluated in similar fashion 1 month later

11 If still no improvement occurs or if at any
time clinical
signs progress, the patient should be evaluated for the
presence of concurrent disorders

12 In dogs whose clinical signs of PDC progress despite l-
deprenyl therapy in the absence of concurrent disease
alternative therapy should be considered

13 Despite the fact that a success rate of 83 has been reported
in the current literature, most clinicians are disappointed
with the results of l-deprenyl therapy

14 The only reported side effect was diarrhea

Important Facts

|Hypothalamic dopamine deficiency has been implicated in the |
|pathogenesis of PDH in the dog |
| |
|L-deprenyl helps restore depleted central dopamine levels and |
|facilitates dopaminergic transmission, increases the synthesis and |
|release of dopamine into the synapse, and inhibits dopamine |
|reuptake |
|
|
|L-deprenyl is only indicated in cases of uncomplicated PDC |
| |
|Perform endocrine functional tests to confirm a diagnosis of PDC |
|before starting therapy with l-deprenyl |
| |
|Start with 1 mg/kg/day for 2 months, if no improvement, increase the|
|dose to 2 mg/kg/day for 1 month, if no improvement, check for |
|concurrent disorders and/or consider alternative therapy |
| |
|Clinical response to therapy has been disappointing |
| |
|Response to therapy is evaluated by history and physical |
|examination An ACTH stimulation test is not necessary |

2 Adrenal Tumors ATs:

a Surgery:

1 Surgery is curative for adrenal adenomas or small carcinomas

2 However, adrenalectomy may be associated with a high rate of
intra-and postoperative complications, including death

3
Complications include cardiac arrest, pulmonary
thromboembolism, acute renal failure, pneumonia, pancreatitis,
and acute adrenal insufficiency

4 If hyperkalemia and hyponatremia occur, oral fludrocortisone
001 to 002 mg/kg daily is administered

5 During and after surgery, large doses of glucocorticoid must
be administered to prevent rapid development of adrenocortical
insufficiency the contralateral adrenal is atrophied

6 Dexamethasone 01 to 02 mg/kg IV is administered
immediately before surgery, immediately after surgery and then
every 6 to 8 hrs in the immediate postoperative period

7 ACTH stimulation test is performed 24 to 48 hrs after surgery

8 Prednisone at the dose of 05 mg/kg twice daily should be
given as soon as possible after surgery The minimal amount
should be given until the remaining gland has regained
function, as determined by the ACTH stimulation test

Important Facts

|Surgery is curative for adrenal adenomas or small carcinomas |
|
|
|Adrenalectomy may be associated with a high rate of intra-and |
|postoperative complications, including death |
| |
|If hyperkalemia and hyponatremia occur, oral fludrocortisone is |
|administered |
| |
|An ACTH stimulation test should be performed 2 to 3 days after |
|surgery to evaluate adrenal reserve and exclude occult metastasis or|
|incomplete resection |
| |
|Glucorticoid has to be administered before surgery, during surgery |
|and after surgery until the remaining gland has regained function |

b Lysodren:

1 Indications for mitotane therapy in cases of ATs are:

a Gross metastic disease evident before surgery

b Unresectable or incompletely resectable tumor

c Residual disease after adrenalectomy

d
Unacceptable anesthetic and surgical risks

e Refusal of surgery by the owner

2 The protocol used to manage PDC will be applied for treatment
of ATs

3 The induction dose is higher 50 to 100 mg/kg and the
induction period is on average longer 10 to 14 days

4 The maintenance dosage is on average higher

Important Facts

|The same protocol used to manage PDC can be used to manage ATs |
| |
|On average, the induction and maintenance dosages will be higher and|
|the induction period longer |

c Ketoconazole:

1 At this time, the primary use for ketoconazole in dogs with
adrenal tumors is preoperative preparation for 4 to 8 weeks
before adrenalectomy

Important Facts

|Drawbacks of ketoconazole therapy include high cost, twice daily |
|administration, and lack of effectiveness in at least half of dogs |

References

1 Guptill L, Scott-Moncrieff JC, Widmer
WR: Diagnosis of canine
hyperadrenocorticism Vet Clin North Am Small Anim Pract 272: 215-235,
1997

2 Kintzer PP Peterson ME: Diagnosis and management of canine cortisol-
secreting adrenal tumors Vet Clin North Am Small Anim Pract 272:299-
307, 1997

3 Bruyette DS, Ruehl WW, Entriken T et al: Management of canine pituitary-
dependent hyperadrenocorticism with l-deprenyl anipryl Vet Clin North
Am Small Anim Pract 272: 273-286, 1997

4 Mack RE, Feldman EC, Wilson SM: Diagnosis of hyperadrenocorticism in
dogs Compend Contin Educ Pract Vet 163: 311-347, 1994

5 Feldman EC Nelson RW 1996 Hyperadrenocorticism Cushings
Syndrome In: Canine and Feline Endocrinology and Reproduction 2nd
ed WB Saunders, Philadelphia pp 187-261

Learning Objectives

1 Know that 85 of the spontaneous Cushings cases are pituitary dependent
and, 15 are caused by an adrenal tumor

2 Know that more than 50 of Cushings cases are iatrogenic

3 Common historical signs associated with Cushings are polyuria,
polydpsia, polyphagia, panting, exercise intolerance and skin and coat
abnormalities

4 Know all the organs affected and physical
findings present on
examination

5 Understand why polyuria, polydpsia, polyphagia, and pot-belly appearance
develop

6 What causes an animal with Cushings to pant?

7 Why are dogs with Cushings prone to develop bacterial cystitis?

8 Why do dogs with Cushings develop hepatomegaly?

9 Why do dogs with Cushings develop proteinuria?

10 Know and understand the abnormalities present in chemistry profile and
urinalysis of a dog with Cushings

11 Remember The ACTH stimulation test is used to diagnose Cushings not
to differentiate pituitary dependent from adrenal tumor This test
evaluates the adrenal reserve of glucocorticoids

12 Remember The ACTH stimulation test has an accuracy of 85 if a dog
has PDC but of only 50 if a dog has AT

13 Remember The ACTH stimulation test is the best test to diagnose
iatrogenic Cushings

14 Know and understand the results of an ACTH stimulation test in a normal
dog, in a dog with spontaneous Cushings and, in a dog with iatrogenic
Cushings

15 Remember The low dose dexamethasone suppression test can diagnose
Cushings in 95 of the cases So, it is more accurate than the ACTH
stimulation test but it is an 8 hour test

16
Remember The low dose dexamethasone suppression test can
differentiate pituitary dependent from adrenal tumor in approximately 40
of the cases Be able to interpret the test results in these cases

17 Know and understand the results of the low dose dexamethasone
suppression test in a normal dog and in a dog with Cushings

18 Remember Dogs with diseases other than Cushings can have ACTh and
low dose dexamethasone suppression test results similar to the results of
a dog with Cushings In other words, false positive results can occur

19 What are the tests used to different pituitary dependent Cushings from
adrenal tumors? How do you interpret the test results?

20 How do you manage pituitary dependent Cushings Be sure to understand
well the protocol of mitotane therapy

21 What are the side effects associated with mitotane therapy? How do you
manage it?

22 What Cushings cases are candidates for l-deprenyl therapy?

23 How do you manage adrenal tumors?

Endocrine Skin Diseases
Hyperadrenocorticism - Feline

A General Consideration:

1 Cushings disease is a rare endocrine disorder in the
cat

2 Pituitary dependent Cushings PDC occurs in 75 to 80 of cases
and, adrenal tumors ATs occurs in 20 to 25 of cases

3 Clinical signs, clinicopathological findings and radiographic
changes are less dramatic in cats which may hinder early diagnosis

4 About 80 of cats with Cushings present with concurrent diabetes
mellitus which contributes to the clinical picture

Important Facts

|Cushings is rare in cats |
| |
|PDC occurs in 75 to 80 and ATs occur in 20 to 25 of cases |
| |
|About 80 of cases are associated with diabetes mellitus, compared |
|with 5 to 10 of Cushings dogs |

B Clinical Signs:

1 Signalment:

a Age: 6 to 15 years old

b Sex: females?

c Breed: no breed predilection

2 Physical findings:

1 Polyuria and polydpsia: 93 of cases This sign can present
before or after the development of diabetes mellitus

2 Pendulous abdomen: 89 of cases

3 Polyphagia: 81 of cases This sign can present before or after
the development of diabetes mellitus

4 Endocrine alopecia: 63 of cases

5 Muscle wasting: 56 of cases

6 Thin Skin: 48 of cases

7 Weight gain: 48 of cases

8 Weight loss: 19 of cases

9 Easily bruised skin: 15 This sign does not occur very often
but, if it is present, include Cushings in your list of rule
outs The skin shows extreme fragility and tears very easily

10 Most cases show clinical signs for 10 months or more before
presentation

Important Facts

|Polyuria, polydpsia and polyphagia are common signs and they may or |
|may not be associated with diabetes mellitus |
| |
|Alopecia occurs in 63 of the cases and, 15 of cats with Cushings |
|will present with an extremely fragile skin |
| |
|Most cases show clinical signs for 10 months or more
before |
|presentation |

C Diagnosis:

1 Diagnosis should be based on:

a History

b Clinical signs

c Clinicopathological abnormalities

d Endocrine evaluation

2 Clinicopathological abnormalities:

a Hyperglycemia and glucosuria is the most common laboratory
abnormality reported to occur in about 80 of cases However,
a recent report of 6 cats with Cushings, describes diabetes
mellitus in only 50 3 of the cases

b Hypercholesterolemia is also common

c Elevation of ALP is present in only 30 of cats compared with
nearly 90 of dogs with Cushings

d SAP and ALT frequently normalize with adequate regulation of
diabetes

e In contrast to dogs, cats only rarely show low urine specific
gravity 1020

f Lymphopenia, eosinopenia and neutrophilia occur inconsistently
in cats with Cushings

Important Facts

3 Endocrine evaluation:

a Screening tests:

1 ACTH stimulation test:

a It has an accuracy of 70 to 85

b A post-ACTH cortisol concentration of 160 mcg/dl or
higher has been considered consistent with Cushings

c Laboratories are encouraged to establish their own
reference values, to avoid using canine or incorrect
reference values

d Stressed cats and cats with nonadrenal diseases may have
an exaggerated response to ACTH

e Protocol:

1 Collect a pre sample and post samples at 1 and 2 hours
after the IM administration of 20
U/kg of ACTH gel

2 Alternatively, plasma is obtained before and 30 to 60
minutes after 0125 mg synthetic ACTH is administered
IM

Important Facts

|ACTH stimulation test has an accuracy of 70 to 80 |
| |
|Stressed cats and cats with nonadrenal diseases may also have an |
|exaggerated response to ACTH |
| |
|The ACTH stimulation test is considered less sensitive than the |
|dexamethasone suppression test as a diagnostic test |

2 Low dose dexamethasone suppression test:

a It is more accurate than the ACTH stimulation test

b Protocol:

1 The test is performed as in dogs

2 01 mg/kg of dexamethasone IV is more reliable than
001 mg/kg to diagnose feline Cushings

3 Determine plasma cortisol levels before and 4 and 8
hours after
administration

c Test interpretation:

1 Post-dexamethasone plasma cortisol levels of 10
mcg/dl or less at 4 and 8 hours are considered
normal

2 Concentrations of 11 mcg/dl to 14 mcg/dl at 4 and 8
hours are considered borderline

3 Concentrations of 15 mcg/dl or more at both 4 and 8
hours are consistent with a diagnosis of Cushings

Important Facts

|Low dose dexamethasone is more accurate than ACTH stimulation test |
|as a diagnostic test |
| |
|mg/kg IV of dexamethasone is more reliable than 001 mg/kg to |
|diagnose feline Cushings |
| |
|Post-dexamethasone cortisol values higher than 15 mcg/kg at both 4 |
|and 8 hours are consistent with a diagnosis of Cushings |
| |
|The cat
should be kept quiet and not disturbed during the 8-hour |
|testing periods |

b Differentiating tests:

1 High dose dexamethasone suppression test:

a The protocol is the same used in the low dose
dexamethasone test, however, the dose is 10 mg/kg IV

b As with the low dose test, the cat should be kept quiet
and not disturbed during the 8-hour testing periods

c Arbitrarily, suppression of post-dexamethasone plasma
cortisol levels is defined as values less than 50 of
baseline Suppression can also be defined as plasma
cortisol less than 15 mcg/dl at 8 hours

d Most cats with Cushings fail to suppress plasma cortisol
levels below 15 mcg/dl at 4 or 8 hours after 10 mg/kg of
dexamethasone

e Lack of suppression, either on a percentage basis 50 of
baseline or using absolute values 15 mcg/dl, is
consistent with a diagnosis of Cushings syndrome but
should
not be thought to confirm a diagnosis of an AT

f Diagnosis of AT is usually suspected on abdominal
ultrasonography

g Suppression using both percentage decrease and an absolute
decrease on 10 mg/kg dexamethasone testing, is documented
in a few cats with PDC but not in those with ATs

Important Facts

|The high dose protocol is the same used in the low dose |
|dexamethasone test, however, the dose is 10 mg/kg IV |
| |
|Compared with dogs, most cats with Cushings do not suppress the |
|post-dexamethasone cortisol levels at 8 hours |
| |
|These cases confirm a diagnosis of Cushings but, should not be |
|considered as ATs cases |
| |
|Few cats will suppress using percentage 50 of baseline and an |
|absolute decrease 15 mcg/dl cortisol value at 8 hour These |
|cases have PDC
|
| |
|If the results are 15 mcg/dl or more and, at the same time, less |
|than 50 of baseline, the interpretation would be PDC suppressed |
| |
| |
|Diagnosis of AT is usually suspected on abdominal ultrasonography |

2 Plasma endogenous ACTH:

a As in dogs, this test can be interpreted reliably only
after the diagnosis has been confirmed with acceptable
screening test results

b Cats normal endogenous ACTH range is 0 to 110 pg/ml

c Three cats reported in the literature with an AT had
undetectable to low plasma endogenous ACTH levels, and 13
cats diagnosed with PDC had ACTH levels that ranged from 9
to greater than 1000 pg/ml mean 281 pg/ml

Important Facts

|As in dogs, this test can be interpreted reliably only after the |
|diagnosis has been
confirmed with acceptable screening test results|
| |
| |
|Undetectable to very low plasma ACTH levels are suggestive of AT |
|and, high levels are indicative of PDC |

3 Abdominal ultrasonography:

a Ultrasonography can be extremely reliable in
differentiating AT unilateral adrenomegaly from PDC
bilaterally normal-sized to bilaterally enlarged
adrenals

Important Facts

|Pituitary-dependent function tests need to be interpreted in |
|conjunction with historical, clinical and clinicopathologic findings|
|before any conclusions can be drawn |
| |
|No single test is infallible |

D Treatment:

1 Cushings disease is very debilitating in cats

2 Although therapy is difficult and the prognosis is guarded, an
attempt is usually made to control the
disease because of the
deteriorating clinical condition of afflicted cats

3 Adrenalectomy, unilateral in cats with AT or bilateral in cats with
PDC, has provided the best results in managing cats with Cushings

4 The surgery protocol and medical management of cats during and
after the procedure are similar to those used in dogs

5 Post-surgical complications contributing to death or euthanasia
include sepsis, pancreatitis, thromboembolic phenomena, wound
dehiscence, and adrenal insufficiency

6 The longest-surviving cats are those that have had an
adrenocortical adenoma or carcinoma removed surgically

7 The most important determinant of long-term prognosis in cats
undergoing adrenalectomy is the ability of the owner and clinician
to successfully manage the iatrogenic adrenal insufficiency

8 Medical therapy has had limited success in the management of feline
Cushings However, it should be considered as a presurgical
preparation option

9 The drugs which could be used are: the adrenolytic drug o,p-DDD,
drugs which block the cortisol
synthesis such as, ketoconazole and
metyrapone, and destruction of the pituitary source of ACTH via
radiation

Important Facts

|Adrenalectomy, unilateral in cats with AT or bilateral in cats with |
|PDC, has provided the best results in managing cats with Cushings |
| |
|The longest-surviving cats are those that have had an adrenocortical|
|adenoma or carcinoma removed surgically |
| |
|The most important determinant of long-term prognosis in cats |
|undergoing adrenalectomy is the ability of the owner and clinician |
|to successfully manage the iatrogenic adrenal insufficiency |
| |
|Medical therapy has had limited success in the management of feline |
|Cushings However, it should be considered as a presurgical |
|preparation option |

References

1 Feldman EC Nelson RW 1996 Hyperadrenocorticism
Cushings
Syndrome In: Canine and Feline Endocrinology and Reproduction 2nd
ed WB Saunders, Philadelphia pp 187-261

2 Watson PJ Herrtage ME Hyperadrenocorticism in six cats Journal
of Small Animal Practice 39, 175-184, 1998

Learning Objectives

1 Know that Cushings is a rare endocrinopathy in cats

2 Remember Most cases in cats 75 to 85 are pituitary dependent

3 Remember More than 50 of cats with Cushings have concurrent diabetes
mellitus, in contrast with dogs in which only 10 have concurrent
diabetes mellitus

4 Know the clinical signs and clinicopathological abnormalities associated
with feline Cushings

5 Remember Extremely fragile and easily bruised skin can be a sign of
Cushings disease in cats However, it has been reported in only 15 of
the cases and it occurs in cutaneous astenia and it can be seen in
exogenously administered glucocorticoids

6 What are the endocrine tests used to diagnose feline Cushings and to
differentiate pituitary dependent from adrenal tumor Know how to
interpret the results

7 Know that adrenalectomy unilateral in cases of ATs and bilateral in
cases of PDC is the best
treatment option for feline Cushings

8 Know the complications associated with surgery Know that the ability
of the owner and clinician to successfully manage the iatrogenic adrenal
insufficiency is very important to decrease post-surgical complications
and death

9 Remember Medical therapy has had limited success in the management of
feline Cushings However, it should be considered as a pre-surgical
preparation option

10 What are the drugs used to treat the disease during the preparation
period for surgery?

Endocrine Skin Diseases
Hyperadrenocorticism - Equine

A General Considerations:

1 Cushings disease is a rare equine endocrine disorder

2 It is usually associated with functional chromophobe adenomas of
the pars intermedia of the hypophysis

3 Hypersecretion of ACTH results in bilateral adrenocortical
hyperplasia that may be diffuse or nodular, or both

Important Facts

|Cushings disease is a rare endocrine disorder in horses |
| |
|It is usually
associated with functional chromophobe adenomas of the|
|pars intermedia of the hypophysis |

B Clinical Signs:

1 Older horses are predisposed

2 It occurs twice as frequently in females than in males

3 Often, attention is first drawn to the disease when the horse
exhibits a rapid regrowth of long hair after a normal shed or fails
to shed a longer than normal winter coat

4 This hirsutism is characterized by an usually symmetric shaggy or
wavy coat up to 10 to 12 cm in length The mane and tail are
unaffected

5 The pathogenesis of the hirsutism is unknown It has been
postulated that increased production of androgens by the
hyperplastic adrenal cortices may be the cause

6 The skin may be dry and scaly or greasy

7 Superficial skin infections dermatophilosis are common

8 Wound healing is delayed

9 The most common clinical signs seen with equine Cushings are
polydipsia and polyuria Some horses will drink over 80L of water
a day

10 Other common clinical signs include muscle wasting, weight loss,
and
lethargy

11 Skeletal muscle wasting often leads to a swayback appearance,
pendulous abdomen, and flaccid musculature

12 Chronic infections, such as abscesses, sinusitis, pneumonia, and
fistulae, are common

13 Occasionally, horses will develop neurologic disorders, blindness,
and thermoregulatory disorders, presumably associated with pressure
on the hypothalamus and optic chiasm by an enlarging pituitary
tumor

Important Facts

|The most common clinical signs seen with equine Cushings are |
|polydipsia and polyuria |
| |
|In most cases, the first clinical sign which calls owners attention |
|is hirsutism |
| |
|Other common clinical signs include muscle wasting, weight loss, and|
|lethargy |
| |
|Skeletal muscle wasting often leads
to a swayback appearance, |
|pendulous abdomen, and flaccid musculature |
| |
|The skin may be dry and scaly or greasy and superficial skin |
|infections are common |
| |
|Chronic infections, such as abscesses, sinusitis, pneumonia, and |
|fistulae, are common |

C Diagnosis:

1 Differential diagnosis: parasitism, inadequate nutrition, poor
dentition, chronic infections, chronic renal or liver disease,
chronic arsenic poisoning, and pheochromocytoma

2 Retention of winter coat can be seen in horses with chronic
illnesses and dietary deficiencies

3 Definitive diagnosis is based on:

a History

b Physical findings

c Clinicopathological abnormalities

d Adrenal functional tests

4 Clinicopathological abnormalities

a Hemograms may reveal neutrophilia, lymphopenia and eosinopenia

b A mild nonregenerative anemia
is common

c Urinalysis usually reveals a low urine specific gravity 1005
to 1017

d Water deprivation tests may result in a marked increase in urine
specific gravity, but the administration of exogenous
antidiuretic hormone ADH does not

e Horses with hyperglycemia may also have glucosuria

f Serum chemistry profile abnormalities may include mild to marked
insulin-resistant hyperglycemia, hypercholesterolemia, and
lipemia

g Basal thyroid hormone levels are usually low These spuriously
low thyroid hormone levels are caused by glucocorticoids and do
not usually indicate concurrent hypothyroidism

Important Facts

|Hirsutism in horses can also be associated chronic illnesses and |
|dietary deficiencies |
| |
|Definitive diagnosis of Cushings should be based on history, |
|physical findings, clinicopathological abnormalities and adrenal |
|functional tests
|
| |
|Clinicopathological abnormalities may include: stress leukogram, |
|mild nonregenerative anemia, low urine specific gravity responsive |
|to water deprivation tests, insulin-resistant hyperglycemia, |
|glucosuria, hypercholesterolemia and lipemia |
| |
|Basal thyroid hormone levels induced by glucocorticoids can occur |
|and, does not indicate concurrent hypothyroidism |

5 Adrenal functional tests:

a The ACTH stimulation test usually confirms a diagnosis of equine
Cushings

b Two commonly used protocols are as follows:

1 Plasma or serum cortisol determinations are made before and 8
hours after the IM injection of 1 IU/kg of ACTH gel or,

2 Plasma or serum cortisol determinations are made before and
two hours after the IV injection of 100 IU of synthetic
aqueous ACTH

3 In normal horses cortisol levels will double to triple their
basal levels

4
Horses with pituitary dependent Cushings will have higher
exaggerated responses

c The dexamethasone suppression test is a less sensitive indicator
of adrenocortical function in the horse

1 In horses, dexamethasone does not have the suppressive effect
on blood cortisol levels that it does in dogs and humans,
presumably because the hypersecretion of ACTH in the horse is
from the pars intermedia rather than the pars distalis and
is relatively insensitive to glucocorticoid negative
feedback

d Plasma endogenous ACTH levels have been measured in normal
horses and horses with pituitary dependent Cushings

1 Normal horses had mean values of 32 /- 5 pg/ml

2 Horses with Cushings had markedly elevated levels:
470 to 4350 pg/ml

Important Facts

|The ACTH stimulation test usually confirms a diagnosis of equine |
|Cushings |
| |
|Horses with Cushings
will more than triple the baseline cortisol |
|levels after the administration of exogenous ACTH |
| |
|The dexamethasone suppression test is not an accurate test to |
|diagnose equine Cushings |
| |
|In horses, dexamethasone does not suppress blood cortisol levels, |
|presumably because the hypersecretion of ACTH in the horse is from |
|the pars intermedia rather than the pars distalis and is |
|relatively insensitive to glucocorticoid negative feedback |
| |
|Horses with Cushings will have markedly elevated endogenous ACTH |
|levels: 470 to 4350 pg/ml, N: 32/-5 pg/ml |

D Treatment:

1 Few horse with Cushings have been treated because of the nature of
the disease, the general severity of clinical signs when the horse
was presented, and economic considerations

2 Several horses have been treated with o,p-DDD, with little or no

benefit

3 Oral cyproheptadine Periactin has been used to treat a few cases
with encouraging results

a The drug has antiserotonin activity and may prevent serotonin-
induced ACTH release

b 58 to 117 mg/450 kg is given every morning

c Beneficial responses were seen within one to two months, and no
side effects were noted

d After 3 months the cyproheptadine was administered every other
morning

4 Another drug used to treat a small number of horses is pergolide

a Pergolide is a dopaminergic agent and an ergot alkaloid

b Potential side effects would relate to intense vasoconstriction,
damage to vascular endothelium, and smooth muscle contraction
eg laminitis

c Regimens ranged from 1 to 5 mg/horse about 001 mg/kg, given
orally, once daily

d Improvement was seen within 2 to 3 weeks

e No side effects were observed

5 The use of cyproheptadine or pergolide to manage equine Cushings
syndrome deserves further investigation

Important Facts

|Few horse with
Cushings have been treated because of the nature of |
|the disease, the general severity of clinical signs when the horse |
|was presented, and economic considerations |
| |
|o,p-DDD therapy has little or no benefit |
| |
|The treatment of equine Cushings with either cyproheptadine, which|
|has an antiserotonin activity, or pergoline, a dopaminergic agent, |
|has had encouraging results |
| |
|The use of cyproheptadine or pergolide to manage equine Cushings |
|syndrome deserves further investigation |

E Prognosis:

1 The prognosis for equine Cushings is poor

2 Many horses suffer a chronic course of progressive debilitation

3 Septicemia, pneumonia, and encephalitis are the usual causes of
death

4 If an owner elects to maintain a horse with Cushings, a high plane
of nutrition, adequate nursing care, and attempts to
minimize
infections are necessary

References

1 Scott DW 1988 Endocrine diseases In: Large Animal Dermatology,
1st ed WB Saunders, Philadelphia pp 374-386

Learning Objectives

1 Know that equine Cushings syndrome is a rare disease and the reported
cases have been due to a functional chromophobe adenoma of the pars
intermedia of the pituitary gland not pars distalis as in dogs and
cats

2 Know that common presenting signs are hirsutism and polydipsia and
polyuria Be able to list the other clinical signs associates with
equine Cushings

3 What are the clinicopathological abnormalities present in equine
Cushings syndrome?

4 Why can low basal T4 and T3 levels be low in horses with Cushings?

5 Know that the ACTH stimulation test usually confirms a diagnosis of
Cushings

6 Why is the dexamethasone suppression test a less sensitive indicator of
adrenocortical function in the horse?

7 Know that because only pituitary dependent Cushings have been diagnosed
in horses, endogenous ACTH measurement can be used as a diagnostic test
remember, it is used to differentiate
pituitary dependent from adrenal
tumor in dogs and cats

8 It is very important for you to know the disease prognosis

9 How do you manage equine Cushings?

Endocrine Skin Diseases
Hypothyroidism - Canine

A General Considerations:

1 Hypothyroidism is the most common endocrine disorder of dogs

2 Before an animal can develop clinical signs of hypothyroidism, more
than 75 of the thyroid gland parenchyma has to be destroyed

3 Canine hypothyroidism is a diagnostic challenge because of the wide
variation in clinical signs

4 The extrathyroidal influences, such as systemic diseases euthyroid
sick syndrome and drug therapies glucocorticoids, potentiated
sulfas etc, have significant effects on thyroid hormone levels

5 Many different assays and function tests have been developed in an
attempt to identify the most sensitive and specific thyroid test
for hypothyroidism

6 Hypothyroidism is overdiagnosed in dogs A great many dogs are
treated with thyroid supplements unnecessarily

Important
Facts

|Hypothyroidism is the most common endocrine disorder of dogs |
| |
|Before an animal can develop clinical signs of hypothyroidism, more |
|than 75 of the thyroid gland parenchyma has to be destroyed |
| |
|The extrathyroidal influences, such as systemic diseases and drug |
|therapies have significant effects on thyroid hormone levels |
| |
|Hypothyroidism is overdiagnosed in dogs A great many dogs are |
|treated with thyroid supplements unnecessarily |

B Etiology:

1 More than 95 of the cases are caused by primary hypothyroidism

a Lymphocytic thyroiditis: It is the most common cause of primary
hypothyroidism It is an immune-mediated disorder It is a
hereditary disorder in colony-raised Beagles

b Idiopathic atrophy of the thyroid gland: Progressive reduction
in the size of the follicles and replacement of the regenerating
follicles with adipose tissue
occur Degeneration of the
follicular cells is seen histologically early in the lesion

c Neoplastic destruction: Clinical signs of hypothyroidism may
develop following destruction of more than 75 of the normal
thyroid gland by an infiltrative tumor Thyroid carcinomas and
squamous cell carcinoma are the most common tumors causing
extensive destruction of the thyroid gland Thyroid carcinomas
or adenomas are usually hormonally inactive and, as a result
clinical signs of hyperthyroidism are uncommon

2 Less than 5 of the cases are caused by secondary pituitary or
tertiary hypothalamic hypothyroidism

Important Facts

|More than 95 of the cases are caused by primary hypothyroidism |
| |
|Lymphocytic thyroiditis is the most common cause of primary |
|hypothyroidism It is an immune-mediated disorder |
| |
|Less than 5 of the cases are caused by secondary pituitary or |
|tertiary
hypothalamic hypothyroidism |

C Clinical Signs:

1 Signalment:

a Age: it occurs most commonly in 4 to 8 year old dogs

b Breed predisposition: Chow Chow, Great Dane, Irish Wolfhound,
Boxer, English Bulldog, Dachshund, Irish Setter, Golden
Retriever, Doberman Pinscher

c Sex: females may be predisposed

2 Classical Signs:

a Symmetrical, nonpruritic alopecia and hyperpigmentation of the
trunk

b Rat tail

c Secondary seborrhea and pyoderma are fairly common; in this
case, there will be some inflammation and pruritus may be
present

d Another dermatologic finding occurs when excessive amounts of
mucopolysaccharides and protein accumulate in the dermis,
causing the myxedematous appearance tragic facial expression
present in some patients

e Obesity: It is a manifestation of low metabolic rate The
degree of obesity is usually moderate, although obesity without
polyphagia is the presenting complaint in some hypothyroid
animals

f Thermophilia: Cold intolerance

g Lethargy: It is a manifestation of low metabolic rate The
presence of lethargy is frequently overlooked in hypothyroid
dogs, with owners noticing the abnormality only after thyroid
hormone supplementation results in increased activity and
alertness

h Weakness and exercise intolerance: Can result from the general
metabolic derangements that occur in hypothyroidism or may be an
indication of a neuropathy or myopathy

i Lethargy, weakness, and exercise intolerance generally resolve
within 2 weeks of initiating treatment unless a neuropathy is
present

j Cardiovascular abnormality: Bradycardia, a weak apex beat, and
poor pulse quality Low-voltage electrocardiographic complexes
occur in more than 50 of hypothyroid dogs, and myocardial
contractility frequently is mildly impaired

k Many cases do not exhibit classical signs

Important Facts

|Classical signs of symmetrical, nonpruritic alopecia and |
|hyperpigmentation of the trunk,
obesity, lethargy, weakness, |
|thermophilia, tragic facies myxedema and cardiovascular |
|abnormalities may not be so classic |
| |
|Many cases do not exhibit classical signs |
| |
|Secondary seborrhea and superficial staphylococcal pyoderma are |
|fairly common, and in these cases, there will be some inflammation |
|and pruritus |

3 Uncommon Signs:

a Neuropathy:

1 Localized neuropathies, resulting in facial and vestibular
neuropathies, megaesophagus, and laryngeal paralysis
Hypothyroidism does not appear to be involved in the
pathogenesis of most cases of laryngeal paralysis

2 Generalized neuropathy can result in progressive generalized
weakness, depression, proprioceptive deficits, and
hyporeflexia

3 Euthyroid dogs with neuropathy or megaesophagus have been
shown to have
suppressed serum T4 and T3 levels, so
establishing a diagnosis of hypothyroidism in these cases is
problematic

b Central nervous system signs:

1 Ataxia, hemiparesis, hypermetria, head tilt, nystagmus,
circling, and dysfunction of multiple cranial nerves can
occur with hypothyroidism

2 The cause is unknown Thyroid hormone supplementation
results in improvement or complete resolution of signs

3 Cerebrovascular atherosclerosis and associated hypoxia or
infarction can result in central nervous system disease in
hypothyroid dogs

c Myxedema stupor or coma:

1 It is a rare, life-threatening consequence of severe
hypothyroidism in adult dogs

2 Signs consist of hypothermia without shivering, marked
depression, bradychardia, hypotension, hypoventilation,
nonpitting edema, and coma in addition to the common signs of
hypothyroidism

d Reproductive abnormalities:

1 Reproductive abnormalities associated with hypothyroidism
have
been poorly documented

2 Overall, hypothyroidism is grossly overdiagnosed as a cause
of reproductive abnormalities

e Ocular abnormalities:

1 Corneal lipid dystrophy, corneal ulcers, anterior uveitis,
and retinopathies have been found in hypothyroid dogs These
are rare signs of hypothyroidism and probably occur only with
prolonged disease

2 Ocular abnormalities reported with hypothyroidism are
probably an effect of hyperlipidemia rather than a direct
result of thyroid hormone deficiency

3 Hypothyroidism should be considered as only one of several
causes of hyperlipidemia associated with corneal lipid
deposition

Important Facts

|Uncommon signs of hypothyroidism include localized or generalized |
|neuropathies, megaesophagus, central nervous system disease, |
|myxedema stupor or coma, reproductive abnormalities, and ocular |
|abnormalities |
|
|
|Euthyroid dogs with neuropathy or megaesophagus have been shown to |
|have suppressed serum T4 and T3 levels, so establishing a diagnosis |
|of hypothyroidism in these cases is problematic |

D Diagnosis:

1 History and clinical signs

2 Clinicopathologic abnormalities:

a Usually nonspecific

b CBC: mild normocytic, normochromic, nonregenerative anemia
present in about 30 of the cases

c Chemistry profile:

1 Fasting hypercholesterolemia present in more than 75 of
the cases

2 Fasting hyperlipidemia and hypertriglyceridemia are also
common

3 Fasting hypercholesterolemia and hypertriglyceridemia can be
associated with several other disorders

4 However, their presence in a dog with appropriate clinical
signs is strong supportive evidence for hypothyroidism

3 Thyroid functional tests:

1 Serum total T4 measurement:

a It is a useful screening test for hypothyroidism

b Serum total T4 measurement represents the sum of the protein-
bound more than 99
of the secreted T4 and free levels
circulating in the blood

c The veterinary hospital laboratory normal range is: 10 to
40 mcg/dl

d Remember Serum total T4 level is below normal range not only
in hypothyroid dogs but also in dogs with normal thyroid
function euthyroid dogs

e The most common situations in which serum total T4 level is
decreased in euthyroid dogs are:

1 Systemic nonthyroidal illness:

a In general, the severity of illness and nutritional
status appear to be the chief factors associated with
decreased serum T4 concentrations

b The decrease in serum T4 level is the bodys attempt to
conserve metabolic resources in the face of disease

c Diseases which have been associated with low basal T4
levels are: renal failure, liver disease, diabetes
mellitus, Cushings syndrome, pyoderma and demodicosis

2 Certain drugs:

a Glucocorticoids, potentiated sulfas inhibit the

synthesis of T4 and T3, phenobarbital, primidone,
furosemide, salicylates, phenylbutazone,
phenothiazines, radiographic contrast agents, flunixin
meglumine, mitotane, diazepam, heparin, imidazoles,
propanolol, penicillins and others

3 In conclusion:

a Low basal T4 values require further evaluation of the
thyroid function This is particularly true in dogs
with unusual signs of hypothyroidism such as neuropathy
or megaesophagus and dogs with non-thyroidal illness

b However, in the absence of concurrent therapy or other
relatively severe illness, measurement of very low T4
levels in a dog with signs of hypothyroidism should
suffice to make a clinical diagnosis

c Measuring serum cholesterol levels and complete blood
cell count, in addition to basal T4 levels, may be more
accurate than just measuring basal T4 levels

Important
Facts

|Normal basal T4 rules out hypothyroidism |
| |
|Low basal T4 is associated not only with hypothyroidism but also |
|with systemic illness and various medications |
| |
|Low basal T4 values require further evaluation of the thyroid |
|function |
| |
|However, in the absence of concurrent therapy or other relatively |
|severe illness, measurement of very low T4 levels in a dog with |
|signs of hypothyroidism should suffice to make a clinical diagnosis|

2 Serum total T3 measurement:

a Hypothyroid dogs often have normal T3 levels

b Most of the serum T3 is derived from peripheral deiodination
of T4

c Serum level of T3 does not reflect cellular concentration

d Serum T3 level is a poor indicator of thyroid function

Important Facts

|Hypothyroid dogs often have
normal T3 levels |
| |
|Serum T3 level is a poor indicator of thyroid function |

3 Serum free T4 measurement:

a Greater than 99 of T4 is bound to plasma proteins

b The unbound or free T4 fT4 is biologically active because
of its ability to diffuse into tissues, penetrate cell
membranes, and interact with receptors

c Accurate measurement of fT4 would transcend the effects that
non-thyroidal illness and drugs have on total T4
concentration and give a more accurate indication of thyroid
status

d Measurement of fT4 by RIA has shown little or no advantage
over measurement of total T4 in diagnosing hypothyroidism

e Measurement of fT4 by equilibrium dialysis is considered the
gold standard test to measure fT4

f A simple technique for measuring fT4 by equilibrium dialysis
is now commercially available

g One study showed that fT4 measured by equilibrium dialysis
remained
normal in most cases with a reduction in T4 and T3
levels induced by non-thyroidal illness

h Before conclusions can be drawn, more studies need to be
conducted to verify the effects of non-thyroidal illness and
drugs on fT4 levels measured by equilibrium dialysis

Important Facts

|The unbound or free T4 fT4 is biologically active because of its |
|ability to diffuse into tissues, penetrate cell membranes, and |
|interact with receptors |
| |
|Accurate measurement of fT4 would transcend the effects that |
|non-thyroidal illness and drugs have on total T4 concentration and |
|give a more accurate indication of thyroid status |
| |
|Measurement of fT4 by equilibrium dialysis is considered the gold |
|standard test to measure fT4 |
| |
|Before conclusions can be drawn, more studies need to
be conducted |
|to verify the effects of non-thyroidal illness and drugs on fT4 |
|levels measured by equilibrium dialysis |

4 TSH stimulation test:

a The TSH stimulation test is a very accurate test to diagnose
hypothyroidism

b Test interpretation:

1 If a dog is normal, the 6-hour post-TSH T4 level should at
least double the pre-value and fall within the laboratory
normal range or,

2 If a dog is normal, the post-TSH T4 levels should be
higher than 45 nmol/L

3 If a dog is hypothyroid, little or no increase in the 6-
hour post-TSH T4 level should be expected or,

4 If a dog is hypothyroid, the post-TSH T4 levels should be
lower than 15 nmol/L

c Disadvantages of the TSH stimulation test:

1 High cost of the bovine TSH

2 Bovine TSH is difficult to acquire

3 It is a 6-hour test

Important Facts

|The TSH stimulation test is a very accurate test to diagnose
|
|hypothyroidism |
| |
|However, the test is expensive, it has a duration of 6 hours and, |
|the bovine TSH used to perform the test is difficult to acquire |

5 Endogenous TSH assay:

a The most recent and exciting development in canine thyroid-
function testing is the production of assays that measure
canine TSH

b Test interpretation:

1 Primary hypothyroidism:

a Endogenous TSH levels should be higher than normal
because the low circulating and pituitary T4 and T3
levels should result in increased TSH secretion
inhibition of pituitary negative feedback mechanism

2 Secondary pituitary level or tertiary hypothyroidism
hypothalamic level:

a Endogenous TSH should be lower than normal pituitary is
not producing or is producing low amounts of endogenous
TSH

c Accuracy of the
test:

1 The accuracy is currently unknown

2 In people, most non-thyroidal illnesses are associated with
normal or decreased serum TSH levels

3 Recent studies in dogs showed that 20 to 40 of hypothyroid
cases have normal serum endogenous TSH levels instead of
the expected high levels

4 15 of dogs with non-thyroidal illness have elevated serum
TSH levels which overlap with values measured in
hypothyroid dogs

5 Dogs treated with potentiated sulfas had increased TSH
after 3 weeks of treatment

6 Values returned to normal range within 3 weeks after
stopping therapy

c Advantages of the endogenous TSH assay:

1 Only one blood sample is required

2 The test is cheaper than the TSH stimulation test

d Test protocol:

1 Blood samples for measurement of total T4 should be
obtained before and 6 hours after intravenous
administration of bovine TSH 01 unit/kg, maximum dose

of 5 units

Important Facts

|The canine endogenous TSH assay was recently developed |
| |
|It is a simpler one blood sample and cheaper test than the TSH |
|stimulation test |
| |
|Endogenous TSH should be higher than normal in hypothyroid dogs and |
|either normal or low in dogs with non-thyroidal illness and |
|receiving medications |
| |
|Unfortunately, recent studies showed that 20 to 40 of dogs with |
|hypothyroidism have normal serum endogenous TSH and, 15 of dogs |
|with non-thyroidal illness have elevated serum endogenous TSH |
|levels |
| |
|Treatment with potentiated sulfas has also shown to lower total T4 |
|and fT4 levels and to increase endogenous TSH levels in the same
|
|manner seen in hypothyroid cases |

6 TRH stimulation test:

a The measurement of total T4 after the exogenous
administration of TRH is not an accurate test to diagnose
hypothyroidism

b Normal dogs and euthyroid dogs with non-thyroidal illness may
fail to show an increase in total T4 levels after the
exogenous TRH administration

c Currently, a TSH assay has been developed for dogs which
allowed the measurement of endogenous TSH after TRH
administration This advent made the TRH stimulation a more
useful test

d TRH stimulation test can differentiate secondary
hypothyroidism pituitary origin from tertiary
hypothyroidism hypothalamic origin

e If a dog has secondary hypothyroidism, the post-TRH TSH
levels should be low to non-detectable

f If a dog has tertiary hypothyroidism, the post -TRH TSH
levels should be normal

g Measurement of TSH after TRH administration can also be
useful
in hypothyroid cases in which serum endogenous TSH,
fT4 or total T4 levels are non-diagnostic

h An exaggerated TSH response to TRH should be expected in
hypothyroid dogs

i Preliminary studies showed that serum TSH peaks 20 minutes
after 200 mcg injection of TRH

j Test protocol:

a Collect blood samples before and 6 hours after intravenous
administration of 05 to 1 mg of TRH Thyrel TRH - Ferring
Laboratories

i Side effects:

a Cholinergic signs, including defecation, vomiting,
urination, and salivation, are common for up to 30 minutes
after TRH administration

Important Facts

|The measurement of total T4 after the exogenous administration of |
|TRH is not an accurate test to diagnose hypothyroidism |
| |
|Normal dogs and euthyroid dogs with non-thyroidal illness may fail |
|to show an increase in total T4 levels after the exogenous TRH |
|administration
|
| |
|The measurement of TSH after the exogenous administration of TRH can|
|be used to diagnose primary, secondary and tertiary hypothyroidism |
| |
| |
|If a dog has primary hypothyroidism an exaggerated TSH response to |
|TRH is expected |
| |
|If a dog has pituitary secondary hypothyroidism, very low or no |
|TSH response to TRH should occur |
| |
|If a dog has hypothalamic tertiary hypothyroidism, a normal TSH |
|response to TRH should be expected |
| |
|Cholinergic signs, including defecation, vomiting, urination, and |
|salivation, are common for up to 30 minutes after TRH |
|administration
|

7 Therapeutic trial:

a It can be used as a diagnostic tool

b Measure basal T4 levels prior to initiating a therapeutic
trial If the total T4 levels are below the normal range,
you can perform a treatment trial dose with T4

c Be very critical when using a treatment trial to diagnose
hypothyroidism

d A 12-week period will allow sufficient time for resolution of
all signs, including hair re-growth, if hypothyroidism is
present

e Take the animal off of thyroid supplementation if resolution
or significant improvement of signs is not observed after 3
months of therapy

f Be aware if pet makes slight improvement Exogenously
administered thyroid hormone can stimulate some hair growth
even in dogs with non-thyroid illness

Important Facts

|Therapeutic trial can be used as a diagnostic tool |
| |
|Be very critical when using a
treatment trial to diagnose |
|hypothyroidism |
| |
|Take the animal off of thyroid supplementation if resolution or |
|significant improvement of signs is not observed after 3 months of |
|therapy |
| |
|Be aware if pet makes slight improvement Exogenously |
|administered thyroid hormone can stimulate some hair growth even in |
|dogs with non-thyroidal illness |

8 Conclusion about the thyroid function tests:

| Currently, the best way to assess thyroid function in dogs is by|
|measuring serum total T4 or fT4 and TSH on a single sample |
| |
|The finding of a low total T4 or fT4 levels with an elevated TSH |
|concentration is diagnostic of hypothyroidism if the animal has a |
|history and clinical findings suggestive of hypothyroidism |
|
|
|Remember, very few studies have been done to determine the effects |
|of non-thyroid illness and medications on these diagnostic tests |
| |
|In a dog that may have concurrent nonthyroidal illness, measurement |
|of serum fT4 by equilibrium dialysis is recommended |
| |
|Critical evaluation of serum TSH assays and measurement of fT4 by |
|equilibrium dialysis as thyroid-function tests is necessary before |
|we can say that the future is here |
| |
|Remember, a therapeutic trial with l-thyroxine can be used to |
|diagnose hypothyroidism but take the dogs off supplementation if |
|clinical signs dont improve significantly or are not resolved after|
|12 weeks of therapy |
| |

E Treatment:

1 Synthetic T4 sodium levothyroxine:

a It is the treatment of choice

b Dose: 002 mg/kg administered twice daily

c Once-a-day administration can be tried after adequate clinical
response is noted

d Modify the initial dose in aged dogs and dogs with diabetes
mellitus, heart failure, renal and hepatic failures

1 Start with 25 of the standard dose

2 Increase dose by 25 every 2 to 4 weeks until the appropriate
dose is reached 002 mg/kg BID

e Monitoring response to therapy:

1 Recheck the animal 6 to 8 weeks after initiation of therapy

2 Critically re-evaluate the clinical response:

a Lethargy and weakness should resolve in 7 to 10 days

b Hair re-growth may take 12 weeks

3 Check post-pill T4 levels at 4 to 6 hours after morning
medication

4 Post-pill T4 values should be at or slightly above the upper
limit of the reference range

Important Facts

|Synthetic T4 is the treatment of choice at the dose of 002 mg/kg |
|given twice daily |
|
|
|Modify the initial dose in aged dogs and dogs with diabetes |
|mellitus, heart failure, renal and hepatic failures |
| |
|Recheck the animal 6 to 8 weeks after initiation of therapy and |
|critically re-evaluate response to therapy: lethargy and weakness |
|should resolve in 7 to 10 days; hair re-growth may take 12 weeks |
| |
|Check post-pill T4 levels at 4 to 6 hours after morning medication |
| |
|Post-pill T4 values should be at or slightly above the upper limit |
|of the reference range |

References

1 Feldman EC Nelson RW 1996 Hypothyroidism In: Canine and Feline
Endocrinology and Reproduction 2nd ed WB Saunders, Philadelphia
pp 68-111

2 Panciera, DL Clinical Manifestations of canine hypothyroidism
Veterinary Medicine, January 1997, p 44-49

3 Panciera, DL Thyroid-function testing: Is the future here?
Veterinary
Medicine, January 1997, p 50-57

4 Panciera, DL Treating hypothyroidism Veterinary Medicine, January
1997, p 58-68

Learning Objectives

1 Remember Hypothyroidism is the most common endocrine disorder in dogs
However, it is overdiagnosed Before clinical signs of hypothyroidism
can develop, more than 75 of the thyroid gland parenchyma has to be
destroyed

2 More than 95 of the cases you will be dealing with in practice will be
caused by primary hypothyroidism likely lymphocytic thyroiditis

3 Remember Hypothyroidism occurs more often in middle age to older dogs
4 to 8 year old dogs Because thyroid hormones are important in cell
metabolism, almost every organ system in the body can be affected
resulting in quite variable clinical signs This makes a clinical
diagnosis a challenge

4 Know the common and uncommon signs associated with canine
hypothyroidism

5 Remember The diagnosis of hypothyroidism should be based on a complete
history, physical findings, clinicopathologic abnormalities and, thyroid
functional tests

6 Remember The clinicopathologic abnormalities are not specific for
hypothyroidism and should
only be used to support a presumptive
diagnosis What are the clinicopathologic abnormalities associated with
hypothyroidism?

7 The total T4 measurement includes the measurements of the protein bound
fraction and the free fraction of the hormone It is the most commonly
requested diagnostic test because it is cheap, involves only one blood
sample collection and, the assay is widely available However, non-
thyroidal illnesses and various drugs can lower total T4 levels and
suggest hypothyroidism to the ones who may not be aware of this fact I
am sure none of you, of course

8 Know the non-thyroid diseases and the commonly used drugs that can lower
total T4 levels

9 How accurate is the fT4 measurement to diagnose hypothyroidism?

10 How accurate is the TSH measurement to diagnose hypothyroidism? How
should the TSH values be normal, high or low in most dogs with
hypothyroidism?

11 Would you request the measurement of total T3 to diagnose
hypothyroidism? Why?

12 In what cases would you request a TRH stimulation test?

13 How accurate is the TSH stimulation test to diagnose hypothyroidism?
Would you have this test performed at the
present time? Why?

14 Remember Be sure the dog has a low total T4 level before starting a
therapeutic trial Recheck your case during the trial and critically
observe response to therapy Signs should significantly improve or
resolve after 12 weeks of therapy

15 In conclusion, hypothyroidism is a challenging disease to diagnose
Your diagnose should be based on a complete history plus clinical signs
plus thyroid function test results Currently, laboratories are
routinely measuring not only total T4 but also, fT4 by equilibrium
dialysis and endogenous TSH Therefore, you have the option of having
these 3 hormones measured on a single blood sample

16 How do you treat hypothyroidism? How do you monitor response to
therapy?

Endocrine Skin Disease
Hypothyroidism - Large Animals

A General Considerations:

1 Naturally occurring hypothyroidism is rare in large animals

2 It is characterized by a plethora of cutaneous and noncutaneous
clinical signs associated with a deficiency of thyroid hormone
activity

B Cause and Pathogenesis:

1 Hypothyroidism may occur
naturally or may be iatrogenic

2 It has been produced experimentally in horses, cattle, goats and
sheep

3 Naturally occurring hypothyroidism in association with dietary
iodine deficiency and goiter has been recognized in all large
animal species

4 Hereditary, congenital goiter and hypothyroidism has been described
in Merino sheep, Afrikaner cattle, and Saanen-Dwarf crossbred
goats

5 Anecdotal or poorly documented reports in the literature suggest
that naturally occurring hypothyroidism in horses may be
responsible for laminitis, infertility, anhidrosis, alopecia,
anemia, myopathy, and osteodystrophy

C Clinical Signs:

1 Animals with hypothyroidism and goiter associated with dietary
iodine deficiency or defective thyroglobulin synthesis are usually
born weak and die within a few hours to a few weeks

2 The hair coat varies from short and fuzzy to completely absent

3 The skin is often thickened and puffy as a result of myxedema,
especially on the head, ear and extremities

4 Merino sheep with hereditary hypothyroidism may
develop a lustrous,
fine, straight silky wool

5 Saanen-Dwarf crossbred goats with hereditary goiter exhibit
retarded growth, decreased ruminations with a tendency for
recurrent bloat, thick and scaly skin, and a sparse hair coat

6 In cattle, surgical thyroidectomy resulted in retarded growth;
lower weight gain per day; calmer attitude; lower body temperature,
heart rate and respiratory rate; decreased ruminal contractions
with a tendency for recurrent bloat; thickened, wrinkled,
myxedematous skin; and a hair coat that was longer, duller, and
thinner than normal

7 In horses, surgical thyroidectomy resulted in retarded growth;
sensitivity to cold shivering; lethargy; decreased rectal
temperature and heart rate; delayed epiphyseal plate closure time
and eruption of incisor teeth; decreased feed consumption and
weight gain; dull, rough hair coat; delayed shedding of winter coat
and edema of the face and distal limbs

D Diagnosis:

1 Diagnosis is based on history, clinical signs, skin biopsy and TSH
or TRH response tests

2
Basal serum total T4 levels have to be used with caution as a
diagnostic tool As in dogs, non-thyroidal illnesses and drugs
especially glucocorticoids and phenylbutazone can lower basal
total T4 levels

3 TSH stimulation test is the gold standard diagnostic test but,
bovine TSH can be very difficult to acquire

4 A commonly used TSH protocol in horses is:

a Collect samples for basal T4 determination before and 6 to 12
hours after the IM injection of 5 IU of bovine TSH or,

b Collect samples for basal T4 determination before and 4 hours
after the IV injection of 5 IU of bovine TSH

c The post-TSH T4 levels in euthyroid horses should be at least
double and should fall within or be above the normal ranges for
the laboratory assaying the samples

5 The TRH response test was reported to be a valuable indicator of
thyroid function in horses

6 TRH given IV at the dose of 05 to 1 mg caused maximal elevations
in serum T4 and T3 levels within 4 to 2 hours, respectively, after
injection

E Treatment:

1 A study
suggested that 10 mg of sodium levothyroxine T4, given
orally, once daily was effective therapy in horses

Important Facts

|Naturally occurring hypothyroidism is rare in large animals |
| |
|Hypothyroidism has been produced experimentally in horses, cattle, |
|goats and sheep |
| |
|Naturally occurring hypothyroidism in association with dietary |
|iodine deficiency and goiter has been recognized in all large animal|
|species |
| |
|Hereditary, congenital goiter and hypothyroidism has been described |
|in Merino sheep, Afrikaner cattle, and Saanen-Dwarf crossbred goats|
| |
| |
|Hypothyroidism is characterized by a plethora of cutaneous and |
|noncutaneous clinical signs associated with
a deficiency of thyroid |
|hormone activity |
| |
|Diagnosis should be based on history, clinical signs, skin biopsy |
|and TSH and TRH stimulation tests |
| |
|L-thyroxine at the dose of 10 mg given orally and once daily has |
|been efficacious to manage the disease in horses |

References

1 Scott DW Endocrine Diseases In: Large Animal Dermatology 1st ed,
1988, p374-386

Learning Objectives

1 Remember Hypothyroidism is a very rare condition in large animals and
it can be experimentally induced or spontaneous

2 Congenital and hereditary hypothyroidism and goiter has been described
in Merino sheep, Afrikaner cattle, and Saanen-Dwarf crossbred goats

3 Naturally occurring hypothyroidism in association with dietary iodine
deficiency and goiter has been recognized in all large animal species

4 Know the various clinical signs presented by the naturally occurring
and
experimentally induced hypothyroidism

5 The diagnosis should be based on history, clinical signs, biopsy and TSH
and TRH stimulation tests Remember The measurement of total T4 levels
can be influenced by many acute and chronic condition and may drugs

6 L-thyroxine at the dose of 10 mg given orally and once daily is
effective to treat horses

Endocrine Skin Diseases
Sex hormone-related alopecias - Canine

A General Considerations:

1 The sex hormone-related alopecias are associated with one of the
following: hypoestrogenism, hyperestrogenism, hypotestosteronism,
hypertestosteronism, and Sertoli cell tumor or other testicular
tumors causing male feminizing syndrome

2 With the exception of Sertoli cell tumor and hyperestrogenism
associated with functional ovarian cysts or tumors, these
diseases are POORLY defined and only named due to therapeutic
responses to various sex hormone supplements It has not been
established that the pathophysiology of these diseases is directly
due to hormone lack or excess

3 Laboratory
measurement of sex hormone levels are of limited
availability, costly, difficult to perform and interpret, may not
be relevant to the disease, and have shown generally poor
correlation with specific disease syndromes

4 Diagnosis of these syndromes rests on demonstrating response to
spaying or neutering in the case of alleged hormone excess, and
response to hormone replacement therapy in the case of alleged
deficiencies

a We usually discourage experimentation with sex hormone
supplementation Once the major endocrinopathies have been
ruled out, owners are often content with the knowledge that
their pets hair loss is cosmetic only

b Risks inherent in sex hormone replacement therapy include bone
marrow suppression diethylstilbestrol and aggressive behavior
and cholestatic liver disease methyltestosterone

5 Consider sex hormone imbalance as a differential in any intact
animal with an endocrine alopecia when Cushings disease and
Hypothyroidism have been ruled out

Important Facts

|Many of
the sex hormone-related alopecias are not well-documented |
|and represent clinical impressions based on response to therapy |
| |
|Laboratory measurement of sex hormone levels are of limited |
|availability, costly, difficult to perform and interpret, may not be|
|relevant to the disease, and have shown generally poor correlation |
|with specific disease syndromes |
| |
|We usually discourage experimentation with sex hormone |
|supplementation Once the major endocrinopathies have been ruled |
|out, owners are often content with the knowledge that their pets |
|hair loss is cosmetic only |
| |
|Consider sex hormone imbalance as a differential in any intact |
|animal with an endocrine alopecia when Cushings disease and |
|hypothyroidism have been ruled out |

I Intact Female

A General Considerations:

1 Sex
hormone-related alopecia in intact females is also called
Ovarian
Imbalance Type I

2 It occurs especially in middle age to older dogs

3 It may be associated with cystic ovaries, or ovarian neoplasia,
or
diethylstilbestrol treatments

B Clinical Signs:

1 Bilaterally symmetric alopecia with or without
hyperpigmentation

2 Pruritus is usually absent but it may be present if seborrhea
oleosa and/or superficial pyoderma occur

3 Estrus cycle abnormalities irregular cycles, prolonged estrus,
and nymphomania often occur, and endometritis or pyometra may
be seen

4 The nipples and vulva are enlarged and comedones are usually
numerous on the ventrum and vulvar skin

C Diagnosis:

1 The primary differential diagnosis include hypothyroidism and
Cushings disease

2 Definitive diagnosis is based on history, physical examination
findings, laboratory test results that rule out other
conditions, and response to therapy

3 Elevated blood estrogen levels
may or may not be present to
support the diagnosis

D Treatment:

1 Ovariohysterectomy

2 A good response is usually evident within 3 months but
occasionally may not be seen for 6 months

3 If an ovarian neoplasm is suspected, chest radiographs should be
taken before surgery

Important Facts

|Remember Consider sex hormone imbalance as a differential in any |
|intact animal with an endocrine alopecia when Cushings disease and |
|hypothyroidism have been ruled out |
| |
|Sex hormone-related alopecia in intact females usually affect middle|
|age to older dogs and, may be associated with ovarian cysts, |
|neoplasia or treatment with diethylstilbestrol |
| |
|Bilaterally symmetric alopecia, abnormal estrus cycles and enlarged |
|vulva and nipples are clinical signs very suggestive of this |
|disorder |
|
|
|Diagnosis should be based on history, clinical signs, laboratory |
|test results that rule out other conditions hypothyroidism and |
|Cushings and response to therapy |
| |
|Elevated blood estrogen levels is not always present to support the |
|diagnosis |
| |
|Response to ovariohysterectomy is usually evident within 3 months |

II Spayed Female

A General Considerations:

1 It is a rare bilaterally symmetric alopecia of unknown etiology
seen in spayed female dogs at a young age

B Clinical Signs:

1 Bilaterally symmetric alopecia usually first noticed when the
dog is a young adult 2 to 4 years

2 The nipples and vulva are often infantile

3 Affected skin is soft and velvet-like

C Diagnosis:

1 Rule out pattern baldness alopecia discussed under
miscellaneous dermatoses, hypothyroidism, and Cushings

disease

2 Definitive diagnosis should be based on history, clinical
signs, laboratory test results that rule out other conditions
and response to therapy

3 Skin biopsy eliminates non-endocrine causes of hair loss, but
otherwise is nondiagnostic

D Treatment:

1 Scientific neglect

2 Diethylstilbestrol at the dose of 01 to 1 mg once daily for 3
weeks, off for 1 week and repeat the cycle until hair regrowth
then 01 to 1 mg once to twice weekly for maintenance

3 Remember to monitor for bone marrow suppression May cause
severe bone marrow depression so use with caution

Important Facts

|Rare disorder seen in young spayed females |
| |
|It presents as bilaterally symmetric non-pruritic alopecia and |
|infantile vulva and nipples |
| |
|Diagnosis should be based on history, clinical signs, laboratory
|
|test results to rule out other conditions pattern baldness |
|alopecia, hypothyroidism, Cushings disease and response to |
|therapy |
| |
|Treatment options include no treatment or supplementation with |
|diethylstilbestrol |
| |
|Monitor closely for bone marrow suppression if using |
|diethylstilbestrol |

III Intact Males - Male Feminization Syndrome

A General Considerations:

1 Male feminization syndrome is usually associated with Sertoli
cell tumor

2 It has been reported to occur in 30 of dogs with Sertoli cell
tumors

3 Seminomas and Interstitial cell tumors can also secrete estrogen
and cause feminization syndrome However, interstitial cell
tumors usually produce testosterone and will cause
hyperandrogenism and seminomas are usually non-functional

tumors

4 Multiple testicular tumors can be present

5 We will discuss Sertoli cell tumor

B Clinical Signs:

1 Functional Sertoli cell tumors are most commonly found in
cryptorchid testicles

2 70 of dogs with testicles located in the abdominal cavity will
develop Sertoli cell tumor and feminization syndrome

3 Feminization is more likely to occur with larger tumors and
tends to be increasingly severe as tumor size increases

4 Approximately 20 of the tumors can be malignant but only about
10 metastasize to the thorax

5 Boxers, Shetland sheepdogs, Weimaraners, Cairn terriers,
Pekingese, and Collies are predisposed

6 The disease usually affects middle-aged to older dogs

7 Specific Signs:

a Bilateral symmetric alopecia begins in perineum and extends
to ventrum, chest, neck, and flanks

b Skin is usually thin and not seborrheic

c Hyperpigmentation may occur and pruritus is only observed if
secondary superficial pyoderma develops

d Linear preputial
dermatosis erythematous line along the
prepuce is a common but not consistent finding

e Pendulous prepuce, gynecomastia, enlarged nipples,
cryptorchid or mass in scrotal testis; uninvolved testicles
are usually atrophied

f Prostate is often enlarged and infected due to estrogen-
induced squamous metaplasia, and there may be clinical signs
referable to prostatomegaly, prostatitis or both

g Behavior changes: attractiveness to other male dogs

h Estrogen-induced bone marrow suppression thrombocytopenia,
neutropenia and anemia is uncommon to rare but is a life-
threatening complication

C Diagnosis:

1 Differential diagnosis:

a As I mentioned before, seminomas and interstitial cell tumors
have been reported to cause identical clinical signs

b Multiple testicular tumors may be present

2 Definitive diagnosis should be based on history, clinical signs,
measurement of basal estradiol levels not always elevated, and
response to castration

3
Radiographs/Ultrasound:

a Abdomen: abdominal mass testis; sublumbar lymphadenopathy

b Thorax: metastases in about 10 of the cases

c Testicles: homogenous mass

D Treatment:

1 Bilateral castration

2 Although the metastatic rate of these tumors is low, all dogs
should be examined carefully before surgery

3 A good clinical response is usually seen within 3 months

4 Remission followed by relapse indicates functional metastases

Important Facts

|Most cases of male feminization syndrome and symmetric non-pruritic |
|alopecia in dogs will be caused by Sertoli cell tumor However, |
|Seminomas and Interstitial cell tumors can rarely cause identical |
|clinical signs |
| |
|Sertoli cell tumor and feminization syndrome occur more often in |
|cryptorchid dogs |
| |
|70 of the cases with abdominal testis will develop Sertoli
cell |
|tumor and feminization syndrome |
| |
|The size of the tumor correlates with the severity of the |
|feminization syndrome |
| |
|About 20 of the cases are malignant and about 10 of the tumors |
|metastasize to the thorax |
| |
|Bone marrow suppression is rare |
| |
|Bilateral symmetric, non-pruritic alopecia begins in perineum and |
|extends to ventrum, chest, neck, and flanks |
| |
|These dogs may show various combinations of feminization signs such |
|as pendulous prepuce, gynecomastia, enlarged nipples and can be |
|attracted by other males |
|
|
|A testicular mass of various sizes may be present in the scrotum, or|
|an abdominal or inguinal mass may be palpated if the dog has |
|cryptorchid testicles |
| |
|After bilateral castration, clinical response is usually seen within|
|3 months |

IV Neutered males-Testosterone-responsive dermatosis of neutered males

A General Considerations:

1 Rare

2 Consider this condition in old dogs castrated at a very young
age

B Clinical Signs:

1 Bilaterally symmetric alopecia usually truncal

2 Coat color change may be present before hair loss is noted

C Diagnosis:

1 The differential diagnosis includes hypothyroidism and Cushings
disease

2 Definitive diagnosis should be based on history, clinical signs
and laboratory test results that rule out other conditions and
response to therapy

3 Skin biopsy shows change compatible with endocrinopathy

D Treatment:

1 Scientific neglect

2 Oral methyltestosterone at the dose of 1 mg/kg up to a maximum
of 30 mg every other day until hair regrowth then give once to
twice weekly

3 Large doses of testosterone may result in seborrhea oleosa,
cholestatic liver disease, and behavior changes aggression

Important Facts

|Testosterone-response alopecia is a very rare condition seen in old |
|dogs neutered at a young age |
| |
|Always rule out hypothyroidism and Cushings disease before |
|considering this condition as a possible diagnosis |
| |
|Discuss with your client the potential side effects associated with |
|testosterone supplementation before starting therapy |

V Seasonal Flank Alopecia

A General Considerations:

1 The pathophysiology of seasonal flank alopecia is unknown

2 The seasonality indicates photoperiod influence probably via
pineal gland
affecting the hypothalamus and pituitary gland
resulting in alteration of thyroid, adrenal and gonadal
hormones

3 Another hypothesis is the presence of abnormal receptors for sex
hormones on the flank skin

B Clinical Signs:

1 Bilateral alopecia more often localized to the thoraco-lumbar
region The lesions are usually annular to polycyclic in shape
and have well-demarcated borders

2 The alopecic skin is usually markedly hyperpigmented

3 In some dogs only one side of the body is affected or one side
is more severely affected than the other

4 Some dogs lose hair in the late fall and regrow it spontaneously
in the spring; others do the reverse and lose hair in the spring
and regrow it in later summer and fall

5 Airedale terriers, English bulldogs and boxers are at higher
risk, but the condition has been described in Miniature
Schnauzers, Miniature Poodles, Doberman pinchers, Bouvier de
Flanders, Scottish terriers, and French bulldogs

C Diagnosis:

1 The differential
diagnosis includes hypothyroidism, Cushings
disease and other sex hormone-related alopecias

2 Definitive diagnosis should be based on history, clinical signs
and laboratory test results that rule out other conditions

3 Skin biopsy shows dysplastic hair follicles which have an
octopus or jelly fish-like appearance Sebaceous glands can be
melanized

D Treatment:

1 There is currently no effective therapy for seasonal or cyclic
flank alopecia

2 Melatonin implants or oral melatonin have been used to manage
this condition with variable results

3 Some dogs continue to develop recurrent seasonal hair loss for
years; other dogs have an occasional year when the alopecia does
not occur; still other dogs eventually develop permanent
alopecia

Important Facts

|The pathophysiology of seasonal flank alopecia is unknown |
| |
|Bilateral alopecia and hyperpigmentation more often localized to the|
|thoraco-lumbar region The
lesions are usually annular to |
|polycyclic in shape and have well-demarcated borders |
| |
|Some dogs lose hair in the late fall and regrow it spontaneously in |
|the spring; others do the reverse and lose hair in the spring and |
|regrow it in later summer and fall |
| |
|Airedale terriers, English bulldogs and boxers are at higher risk, |
|but the condition has been described in other breeds |
| |
|Diagnosis should be based on history, clinical signs and laboratory |
|test results that rule out other conditions |
| |
|Skin biopsy shows dysplastic hair follicles which have an octopus or|
|jelly fish-like appearance Sebaceous glands can be melanized |
| |
|There is currently no effective therapy for seasonal or cyclic flank|
|alopecia
|

References

1 Scott, Miller and Griffin: Chapter 9, Small Animal Dermatology, 5th ed,
1995

2 Scott DW Seasonal Flank Alopecia in Ovariohysterectomized Dogs
Cornell Vet, 1990

3 Miller WH Sex Hormone-related Dermatoses in Dogs In Kirk RW ed
Current Vet Therapy Small Animal Practice Vol X, Philadelphia; WB
Saunders, 1989:595-606

Learning Objectives

2 With the exception of Sertoli cell tumor and hyperestrogenism
associated with functional ovarian cysts or tumors, these diseases are
POORLY defined and only named due to therapeutic responses to various sex
hormone supplements It has not been established that the
pathophysiology of these diseases is directly due to hormone lack or
excess

3 Laboratory measurement of sex hormone levels may not be relevant to the
disease, and have shown generally
poor correlation with specific disease
syndromes

4 Diagnosis of sex hormone-related alopecias should be based on history,
clinical signs, laboratory test results that rule out other hormone-
related alopecias and response to treatment castrate or spay intact
animals and consider sex hormone supplementation in castrated or spayed
animals

5 We usually discourage experimentation with sex hormone supplementation
Once the major endocrinopathies have been ruled out, owners are often
content with the knowledge that their pets hair loss is cosmetic only

6 Consider sex hormone imbalance as a differential in any intact male or
female with an endocrine alopecia when Cushings disease and
hypothyroidism have been ruled out

7 Remember Not only sertoli cell tumors, but also interstitial cell
tumors and seminomas can cause feminization syndrome

8 Intact males with symmetric, non-pruritic alopecia and with clinically
and histologically normal testicles can regrow hair after castration
This condition has been called castration responsive alopecia

9 Airedale terriers, English bulldogs, boxers and also other breeds will
develop seasonal or cyclic
thoraco-lumbar alopecia and hyperpigmentation
Some dogs lose hair in the late fall and regrow it spontaneously in the
spring; others do the reverse and lose hair in the spring and regrow it
in later summer and fall

10 Read and understand well each of the sex hormone-related alopecias
discussed above

Endocrine Skin Diseases
Adult-onset growth hormone responsive dermatosis - Canine

A General Considerations:

1 Adult-onset growth hormone response alopecia is also called Pseudo-
Cushings Syndrome and Adrenal Sex Hormone Imbalance

2 It is seen especially in young male dogs at the age of 1 to 3
years

3 Females can also be affected

4 Dogs can be intact or neutered

5 There is breed predilection for Chow Chows, Pomeranians,
Keeshondens, Samoyeds and miniature poodles

Important Facts

|Adult-onset growth hormone response alopecia is seen especially in |
|young male dogs at the age of 1 to 3 years |
| |
|Females and intact or neutered can be affected
|
| |
|The condition is seen primarily in Chow Chows, Pomeranians, |
|Keeshondens, Samoyeds and miniature poodles |

B Pathogenesis:

1 Cause is unknown Genetic factors may play a role since certain
breeds are more often affected and it may occur in related dogs

2 Evidences suggesting that hyposomatotropism is the cause of the
alopecia:

a Hair regrows in some cases with either human, bovine or swine
growth hormone supplementation

b Many cases have complete or partial lack of growth hormone
response after xylazine or growth hormone releasing factor both
stimulate growth hormone increases

c Decreased dermal elastin fibers seen in some dogs finding
present in growth hormone deficiency

3 Evidences suggesting that hyposomatotropism is not the cause of the
alopecia:

a Many affected dogs have normal growth hormone or somatomedin C
concentration

b Decreased elastin fibers not always present

c Not all
dogs respond to growth hormone supplementation

d Not only pomeranians with growth hormone responsive alopecia but
also normal coated pomeranians had markedly decrease growth
hormone responses to xylazine and growth hormone releasing
factor These dogs also had abnormal increased adrenal sex
hormone concentrations after ACTH stimulation Adrenal Sex
Hormone Imbalance

e Affected dogs of other breeds also have increased sex hormone
concentrations after ACTH stimulation

f Some cases respond to neutering and o,pDDD Mitotane,
Lysodren

4 In conclusion What a confusion:

a Since dogs may have low growth hormone response to xylazine or
growth hormone releasing factor and may have elevated adrenal
progestin and androgen responses to ACTH and may respond to
castration both hyposomatotropism and sex hormone imbalance may
be contributing to the hair loss and hyperpigmentation

Important Facts

|Cause is unknown Genetic factors may play a role since certain |
|breeds are more often affected and
it may occur in related dogs |
| |
|Since dogs may have low growth hormone response to xylazine or |
|growth hormone releasing factor and may have elevated adrenal |
|progestin and androgen responses to ACTH and may respond to |
|castration both hyposomatotropism and sex hormone imbalance may be |
|contributing to the hair loss and hyperpigmentation |

C Clinical Signs:

1 Normal coat until 1 to 3 years of age; then loss of guard hairs;
later alopecia of neck, perineum, caudal dorsal back, caudal
thighs

2 Hyperpigmentation is often intense

3 Head and legs are usually spared

Important Facts

D Diagnosis:

1 Definitive diagnosis should be based on history, clinical signs,
laboratory test results that
rule out other endocrinopathies
primarily Cushings, hypothyroidism and sex hormone imbalance in
intact dogs Biopsy can be helpful if reduced elastin fibers can
be demonstrated

2 Growth hormone stimulation with either clonidine or xylazine is not
currently available

3 ACTH response test to measure adrenal-sex hormone panel:

a Collect baseline EDTA 20 ml blood and clot 50 ml tube
samples

b Centrifuge and remove the plasma from the EDTA tube as quickly
as possible cortisol binds to RBCs

c Centrifuge and remove serum from clot tube as soon as the sample
has clotted Freeze serum

d Administer ACTH Cosyntropin at a dose of 05 IU/kg,
intravenously Alternatively ACTH gel at a dose of 22 mg/kg
IM

e Collect post-samples 20 ml EDTA tube and 5 ml clot tube 1
hour after ACTH administration If ACTH gel is used collect 1
and 2 hour post ACTH samples

f Freeze plasma and serum; ship on dry ice by overnight express
mail to the Endocrinology laboratory at:

Clinical
Endcrinology Lab, Department of Environmental
Practice, 3407 River Drive, RM A 105, VTH, Knoxville, TN
37996, 615 546-6092 or 9230, ext 173

g The following hormones or biosynthetic intermediates are
measured before and after ACTH administration: cortisol, 17-
hydroxyprogesterone,
h progesterone, estradiol, testosterone, dehydroepiandrosterone
sulfate DHEAS, and androstenedione

i Affected dogs have elevated progesterone, 17-
hydroxyprogesterone and androstenedione or DHEAS levels before
and after ACTH administration when compared to normal dogs

j Androstenedione and DHEAS are androgens DHEAS are almost
exclusively produced by the adrenal gland In male dogs 50 of
androstenedione is produced by the adrenal gland and 50 is
produced by the testes

Important Facts

|Definitive diagnosis should be based on history, clinical signs, |
|laboratory test results that rule out other endocrinopathies |
|primarily Cushings, hypothyroidism and sex hormone imbalance in |
|intact dogs
and biopsy |
| |
|Growth hormone stimulation with either clonidine or xylazine is not |
|currently available |
| |
|ACTH response test to measure adrenal-sex hormone panel is available|
|as a diagnostic tool |
| |
|Some affected dogs will have elevated progesterone, 17- |
|hydroxyprogesterone and androstenedione or DHEAS levels before and |
|after ACTH administration when compared to normal dogs |

E Treatment:

1 Scientific neglect

2 Try neutering if the animal is intact

3 Growth hormone supplementation:

a Either human, bovine or porcine growth hormone at the dose of
015 IU/kg 3 times weekly for 4 to 6 weeks

b Hair regrowth should occur within 3 months

c Clinical response usually last 6 months to 2 years so
retreatment may be necessary

d Growth hormone is DIABETOGENIC so baseline and weekly fasting
blood glucose levels should be evaluated during therapy

e Growth hormone is intermittently available from: Dr AF
Parlow, Pituitary Hormones and Antisera Center, Harbor-UCLA
Medical Center, Torrance, CA 90509, 213 533-3537

f To reconstitute growth hormone:

1 Use sterile saline and gently heat vial in 37C water bath
until growth hormone solubilizes

2 Draw up the amount needed per dose in syringes then freeze
the syringes until needed

4 o,pDDD or Lysodren:

a Perform first an ACTH response test measuring adrenal sex
hormones

b After demonstrating that adrenal progestins and androgens are
elevated see Diagnosis this section, start Lysodren

c Induction:

1 15 to 25 mg/kg/day for 7 days

2 Do an ACTH stimulation test on day 7 Post-cortisol should
be about 5 mcg/dl or 50 ng/dl

d Maintenance:

1 15 to 25 mg/kg weekly or bimonthly

e Hair regrowth may be partial or complete

f
Addisons disease is a potential sequela to this treatment
regimen

g Three weeks after initiation of therapy with Lysodren, repeat
the ACTH response test for cortisol only You should still see
adequate suppression of cortisol about 5 mcg/dl You should
also perform a physical examination and electrolytes and
chemistry panel to determine the adverse effects from Lysodren
and/or hypocortisolemia

h At 10 weeks after starting Lysodren repeat the ACTH response
test for both cortisol and adrenal sex hormones

5 Methyltestosterone:

a Dose: 1 mg/kg max 30 mg/dog orally every other day up to 3
months then reduce to twice weekly administration

b Methyltestosterone has been associated with cholangiohepatitis,
behavior changes and seborrhea oleosa

Important Facts

|Scientific neglect |
| |
|Try neutering if intact |
|
|
|Growth hormone supplementation, lysodren therapy or |
|methyltestosterone therapy are treatment options |
| |
|Be careful when choosing any of these treatment modalities due to |
|serious potential side effects associated with each one of them |

References

1 Scott, Miller Griffin: Chapter 9, Small Animal Dermatology 5th ed,
1995

2 Lothrop, CD Jr: Pathophysiology of growth hormone responsive
dermatosis Compend Cont Ed 1998; 1346-1352

3 Parker WM and Scott DW: Growth hormone responsive alopecia in the mature
dog: A discussion of 13 cases JAAHA 166: 824-828, 1980

4 Schmeitzel LP Lothrop CD Jr : Hormone abnormalities in pomeranians
with normal coat and those with growth hormone responsive dermatosis
JAVMA 1990; 15: 1333-1341

5 Schmeitzel LP Sex hormone-related and growth hormone-related
alopecias Vet Clin North Am Small Animal Practice 1990; 20: 1579-
1601

Learning Objectives

1 Know that growth hormone responsive alopecia is seen especially in young

male dogs at the age of 1 to 3 years However, females can also be
affected The disease has been recognized in intact or neutered animals
There is breed predilection for Chow Chows, Pomeranians, Keeshondens,
Samoyeds and miniature poodles

2 Cause is unknown Genetic factors may play a role since certain breeds
are more often affected and it may occur in related dogs

3 Since dogs may have low growth hormone response to xylazine or growth
hormone releasing factor and, may have elevated adrenal progestin and
androgen responses to ACTH and may respond to castration both
hyposomatotropism and sex hormone imbalance may be contributing to the
hair loss and hyperpigmentation

4 Clinical signs are characterized by alopecia and severe
hyperpigmentation of neck, perineum, caudal dorsal back, caudal thighs
Head and legs are usually spared

5 Know that definitive diagnosis should be based on history, clinical
signs, laboratory test results that rule out other endocrinopathies
primarily Cushings, hypothyroidism and sex hormone imbalance in intact
dogs and biopsy Remember that growth hormone stimulation with either
clonidine or xylazine is not
currently available ACTH response test to
measure adrenal-sex hormone panel is available as a diagnostic option
Some affected dogs will have elevated progesterone, 17-
hydroxyprogesterone and androstenedione or DHEAS levels before and after
ACTH administration when compared to normal dogs This test is very
expensive about 18000

6 If you have ruled out other endocrinopathies, you do not need to treat
these cases

7 Neutering intact animals is always a good diagnostic and treatment
trial

8 If the dog has been neutered and/or the owner wants to try medical
therapy the options are: human, bovine or porcine growth hormone
replacement; Lysodren therapy after performing an ACTH stimulation test
to measure adrenal sex hormones; methyltestosterone therapy

9 Remember If you choose any of these treatment modalities be sure to
discuss potential side effects with clients before initiating therapy
MONITOR for adverse effects

Source:wintertrails.org

del.icio.us:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

digg:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

spurl:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

newsvine:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

blinklist:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

furl:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

reddit:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

fark:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

Y!:Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. ...

Diabetes Treatments

Glycosuria and diabetes mellitus occur in about 10% of the cases. SAP and ALT frequently normalize with adequate regulation of diabetes. …

Recent Diabetes Treatments Articles

Categories