Endocrine skin diseases (Proceedings)

Cutaneous manifestations of internal disease exist in both human and veterinary medicine. Many endocrine skin diseases start with bilaterally symmetrical alopecia as the first clinical and presenting sign.

The Master gland of the endocrine system is the pituitary gland. The anterior portion of the pituitary is the most important part of the gland concerning dermatologic diseases. Anterior Pituitary Hormones include TSH, ACTH, FSH, LH, B-lipoprotein, Prolactin and GH.

Hypothyroidism

Hypothyroidism is a common multisystemic disease that is present in dogs and even occasionally in cats. It occurs predominately in the middle aged purebred dogs including the Golden retriever, Doberman Pinscher, Irish setter, Boxer, Miniature schnauzer, Dachshund and Cocker spaniel.

Hypothyroidism is the most common endocrine dermatosis, but also the most commonly overdiagnosed. Primary atrophy and destruction of the thyroid gland is the most common cause of hypothyroidism. Lymphocytic thyroiditis is an immune mediated destruction of the glandular tissue. Circulating antithyroglobulin antibodies are present in many cases. Idiopathic thyroid gland atrophy can also be seen. In these cases the thyroid follicles are replaced with adipose tissue without inflammation. Secondary and tertiary hypothyroidism is very rare.

• In the body, the thyroid hormone T4 is converted to T3, the major active hormone and reverse T3, which is inactive.

• In cases of hypothyroidism, epidermal atrophy and abnormal keratinization is present. There is also decreased protein synthesis, abnormal lipogenesis and decreased sterol synthesis of keratinocytes. There are decreased anagen hairs, increased Glyscosaminoglycans in the dermis. Recurrent superficial bacterial pyoderma is common. Symmetrical alopecia, dull, dry pelage that fails to grow after clipping, variable hyperpigmentation, cool, dry skin that easily bruises and

• Seborrhea are many of the cutaneous signs.

• Other clinical signs include weight gain, lethargy, cold intolerance, weakness, peripheral neuropathy, bradycardia, impaired myocardial contractility, decreased QRS amplitude, anestrus, lack of libido, corneal lipid deposits, and KCS.

• Screening laboratory tests show normocytic, normochromic anemia, hypercholesterolemia, hypertriglyceridemia (less common).

• Serum T4, fT4, T3, fT3, rT3, antithyroglobulin antibodies and endogenous TSH are all available. TSH response and TRH stimulation are no longer available for private veterinary practitioners.

• Low T4 levels are seen in hypothyroidism, sick euthyroid syndrome GCC, anticonvulsants, potentiated sulfas drugs and androgens/estrogens.

• Preliminary data shows that running fT4 and tT4 may increase accuracy by 10-15%. however measuring fT4 alone has no greater value than tT4 by itself.

• Endogenous TSH levels should be elevated in primary hypothyroidism and low in sick euthyroid syndrome. Antithyroid antibodies include measurement of antithyroglobulin antibodies and antibodies to T3

• Treatment of Hypothyroidism is L-T4 at a dose of 0.01-0.02 mg/kg bid

• Large dogs may be dosed at 0.5 mg/m2 bid. Post-pill T4 should be monitored

• L-T3 therapies and L-T3/L-T4 combination therapies are not recommended

Hyperadrenocorticism

• Cushings Syndrome is a collection of clinical signs and biochemical abnormalities that result from chronic exposure to GCC excess.

• The three forms of Hyperadrenocorticism are pituitary-dependent, adrenal tumors, and Iatrogenic. Middle-aged to older dogs, especially

• Poodles, dachshunds, Boston terriers, and boxers are predisposed.

• 70% of adrenal tumors are seen in female dogs.

• Cutaneous signs include pendulous abdomen, bilateral alopecia, dry pelage, skin atrophy, hyperpigmentation, muscle and testicular atrophy.

• Calcinosis cutis, demodicosis and recurrent pyoderma are often seen in Cushingnoid dogs.

• Hyperadrenocorticism may be associated with panting, pulmonary thrombosis PU/PD (often the initial sign), urinary tract infections, polyphagia and Insulin resistant DM

• Radiography commonly shows hepatomegaly and 1/3 adrenal tumors mineralize.

• CT and MRI scans may show pituitary tumors if greater than 1 cm and considered the most accurate away to image adrenal glands. Ultrasound may also image enlarged or nonsymmetrical adrenal glands

• Diagnosing hyperadrenocorticism usually involve Pituitary-Adrenal function tests.

• Basal cortisols are not accurate and are not recommended

• ACTH stimulation is an adrenal function test that measures the relative thickness of the adrenal cortex. 85% of PDH cases show exaggerated cortisol response. Blunted response is associated with iatrogenic Cushings.

• 50% of adrenocortical tumors show an exaggerated cortisol response

• ACTH gel is given intramuscularily with samples drawn prior to admistration and 2 hours post. The Low Dose Dexamethasone suppression test has 90% sensitivity but does not always differentiate between PDH and adrenal tumors.

• Clinicians should use dexamethasone sodium-phosphate (0.015mg/kg) as their dexamethasone source. Samples for cortisol determination are taken at 0, 4, 8 hours. High dose dexamethasone suppression test is primarily useful for differentiating between PDH and adrenal tumors. 15% of PDH do not suppress using the High Dose Dexamethasone suppression.

• The clinician should use dexamethasone sodium phosphate at a dose (0.1- 1.0mg/kg). Samples for cortisol determination are again taken at 0, 4, 8 hours.

• Elevated plasma ACTH (>40) distinguishes between PDH and adrenal tumors. Low levels of ACTH are seen with adrenal tumors. This is an expensive test; samples must be centrifuged and frozen in plastic, sent overnight on dry ice.

• Dermatopathology show hyperkeratosis, epidermal atrophy, follicular atrophy/dilatation, sebaceous gland atrophy, telogenezation of follicles, and dystrophic mineralization.

• The goal of medical management of PDH is to achieve subclinical hypoadrenocorticosm. The drugs of choice are Mitotane (o,p-DDD or Lysodren) or Trilostane (Vectoryl).

• Nizoral and Deprenyl may also be used but have not been as effective. Surgical removal of adrenal tumors should be performed when identified.

• o,p-DDD (Lysodren) causes necrosis of zona fasiculata and reticularis of adrenal cortex. Loading dose is 25-50mg/kg/day for 7-10 days, with maintenance every 5-7 days. Mitotane absorbtion is enhanced by food(especially fat). Side effects include lethargy, V/D, and anorexia. An ACTH stimulation is performed at the end of the 7-10 day loading period. Lifelong maintenance is usually required.

• Trilostane (5-10 mg/kg up to 40-50 mg/kg divided bid) is a new medication that may become the treatment of choice. It is available at Wedgewood Pharmacy (800) 331-8272. This is a daily medication that interferes with glucocorticoid production at the enzymatic level. Monitoring is done with ACTH stimulation similar to Lysodren. It is best to do the test 4-6 hours after the morning Trilostane administration. It is give daily as a lifetime medication.

Sex Hormone Associated Dermatoses

These cases are associated with sex hormone imbalances. It is important to always rule out hypothyroidism and hyperadrenocorticism first.

Estrogens are produced by ovaries, testes, adrenal cortex and peripheral conversion of androgens. May cause increased or decreased epidermal thickness, decreased subcutaneous fat and dermis, hair growth and sebaceous glands. Hyperestrogenismia often associated with cystic ovaries, tumors are rare

• Are Bulldogs predisposed?

• Clinical signs may include alopecia of perineal, flank and inguinal regions

• Nipples and vulva may be enlarged

• OHE is curative

Other estrogen disorders include the Sertoli cell tumor, interstitial cell tumors and seminomas. Endocrine alopecia and feminization are common.

• These tumors are more common in cryptorchids

• Boxers, Shelties, Weinmaraners, Cairns, Collies are predisposed.

• Alopecia of trunk and collar, gynecommastia, linear preputial dermatosis are often presenting signs. Bilateral castration is treatment of choice.

• Metastases are rare but can occur. Resolution is seen within 3-6 months