So called alopecia-X or We all know it when we see it, but what is it really (Proceedings)

Growth Hormone - Responsive Dermatosis (Adult-Onset Hyposomatotropism, Pseudo-Cushing's Syndrome)

• Etiology

• Unknown

• Possible deficiency in growth hormone that develops after maturity

• Atrophy of pituitary gland in one case

• Adrenal sex hormone abnormality

• Breed Predilection - Chow Chows, Keeshond, Pomeranian, Miniature Poodle

• Age Predilection - 1-3 years old

• Sex Predilection - intact male dogs

• Clinical Features

• Bilaterally symmetrical alopecia and hyperpigmentation - primarily neck, perineal and genital regions, tail, posterior and medial thighs, ventral abdomen

• Excess scaling and dull, dry hair coat

• Fuzzy hair coat

• Changes in hair coat color

• Regrowth of hair in areas of full thickness trauma to the skin

• Appears clinically similar to castration responsive dermatosis

• Diagnosis

• Skin biopsy - consistent with endocrinopathy, presence of eosinophilic tricholemmal keratinization ("flame follicles").

• Growth hormone stimulation test - see pituitary dwarfism.  Low or normal baseline growth hormone levels with a poor response to stimulation (xylazine) can be normal for Pomeranians.

• Must differentiate from castration responsive dermatosis - (measure serum estradiol, progesterone, and testosterone) and adrenal sex hormone dermatosis.

• Treatment

• Growth Hormone treatment (bovine) - 2.5 units (less than 14 kg) - 5.0 units (greater than 14 kg) SQ every other day for 10 injections.

• Should see response within 3 months

• Effective for 6 months to 3 years

• Many cases have not responded completely

• May induce diabetes mellitus, acromegaly

• Hormone is very difficult to obtain

• Human Growth Hormone - 0.15 IU/kg SQ twice weekly for six weeks

Castration Responsive Dermatosis

• Etiology - A mild to moderate elevation of serum estradiol in intact male dogs

• Histologically normal testicles with normal descent of testicles

• Sex Predisposition - intact male dogs

• Breed Predisposition - Pomeranian, Chow Chow, Miniature Poodle, Keeshond

• Clinical Features

• Bilaterally symmetrical alopecia and hyperpigmentation - affects the neck, perineal and genital region, tail, posterior and medial thighs, ventral abdomen

• Excess scaling and dull, dry hair coat, Fuzzy hair coat, Changes in hair coat color, Regrowth of hair in areas of full thickness trauma to skin

• History of normal descent of testicles that palpate normal on physical examination

• Diagnosis

• History and physical examination

• Reproductive hormones

• Mild to moderate elevations in estradiol

• Also measure progesterone and testosterone

• GnRH response test - 0.1 ug/lb GnRH (Cystorelin) IV, take baseline + 1 and 2 hour post-GnRH samples

• May have multiple endocrine abnormalities revealed on TSH response test, cortisol function test, growth hormone stimulation tests

• Skin biopsy

• Consistent with an endocrinopathy, Brightly eosinophilic tricholemmal keratinization ("flame follicles")

• Testicular biopsy – normal

• Treatment

• Castration - response in 2-3 months

Adrenal Sex Hormone Dermatosis

• Etiology

• Defect in adrenal steroidogenesis, A partial 21-hydroxylase enzyme deficiency proposed, Results in increased serum progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone (DHEAS), androstenodione, Elevated basal plasma ACTH

• Sex Predisposition - intact male and female dogs

• Breed Predisposition - Pomeranians, Chow Chows, Keeshonds, Samoyeds

• Clinical Features

• Bilaterally symmetrical alopecia and hyperpigmentation - affects the neck, perineal and genital region, tail, posterior and medial thighs, ventral abdomen

• Excess scaling and dull, dry hair coat, Fuzzy hair coat, Changes in hair coat color, Regrowth of hair in areas of full thickness trauma to the skin

• Appears clinically similar to Growth Hormone - Responsive Dermatosis and Castration Responsive Dermatosis

• Diagnosis

• History and physical exam

• ACTH stimulation test - Reproductive hormone panel

• Baseline EDTA and clot tube samples

• Give 0.5 IU/kg ACTH (Cosyntropin) IV

• Collect 1 hour post-ACTH samples

• Samples measured for cortisol, 11-deoxycortisol, DHEAS, androstenedione, 17-hydroxyprogesterone, progesterone, testosterone, and estradiol

• Growth hormone stimulation test - may have concurrent poor responsiveness to xylazine stimulation

• Skin biopsy - consistent with and endocrinopathy, presence of eosinophilic tricholemmal keratinization ("flame follicles")

• Treatment

• o.p'-DDD (Lysodren) - 15-25 mg/kg, SID for 5 days, then q 7-14 days as maintenance

• Monitor cortisol function with ACTH response test

• Ketoconazole (Nizoral) - 30 mg/kg, divided BID-TID

• Decreases cholesterol synthesis, decreases serum basal cortisol and testosterone, Increases serum basal progesterone and 17-hydroxyprogesterone

• Growth hormone treatment

• Methyltestosterone - 0.5 mg/lb q 48 h (maximum dose of 30 mg/dog) x 30-60 days, then 1-2x weekly.

• Melatonin – 3-6 mg/dog TID

• Trilostane – 5-10 mg/kg/day

Alopecia X – Latest Theories

• Follicular growth dysfunction of plush-coated breeds

• Primary hair follicle receptor defect

• Abnormal receptor response to a normal hormone signal - Similar to male pattern baldness

• Genetically determined disease

• Multi-genetic trait, Pomeranians as the prototype

• May be similar in the Chow Chow, Keeshond, Samoyeds, Siberian Husky, Alaskan Malamute

• Selective breeding for the trait neotony - Retention of the juvenile prototype, Retention of the “puppy coat” (plush coat)

• Mild but prolonged increase in basal cortisol

• Normal ACTH response tests, Increased urinary cortisol/creatinine ratio, Slightly enlarged adrenals on abdominal ultrasound

Alopecia X – Treatment Approach

• Castration or OHE - Treatment of choice if intact

• Melatonin

• Alters sex hormone levels, Increase in growth hormone factors

• 1-6 mg/dog TID

• Lethargy, insulin resistance

• Benign neglect - only an aesthetic disease – “Buy the dog a sweater”

• Testosterone

• 1 mg/kg q48h (max dose of 30 mg/dog) x 30-60 days, then 1-2 x weekly

• Potentially Hepatotoxic

• Finasteride (Propecia®, Proscar®)

• 5 alpha-reductase inhibitor, Block DHT production

• 5 mg/dog – SID

• Leuprolid acetate (Lupron®)

• Synthetic analog of GnRH

• Causes decreased endogenous GnRH production, decreased FSH and LH, decreased sex hormones

• 100 ug/kg IM   q 4-8 weeks

• Panting, anxiety – “hot flashes”

• Topical Cyproterone –blocks DHT receptors

• Mitotane (Lysodren®)

• 15-25 mg/kg – SID x 5 days, then q 7-14 days as maintenance

• Hypoadrenocorticism potential

• Trilostane (Vetoryl®, Modrenal®)

• 5-10 mg/kg SID

• Dogs with cardiac disease at risk

• Hypoadrenocorticism potential

• Cyclosporine (Atopica®)

• 5 mg/kg SID

• Vomiting/diarrhea

• Gradually increase dosage

• Metoclopramide (Reglan®) – 0.2-0.5 mg/kg TID

• Maropitant citrate (Cerenia®) – 2 mg/kg SID, 1 hour prior to cyclosporine x 4 days.

• Psoriasiform-Lichenoid drug eruption, Gingival hyperplasia, Hypertrichosis

• Increased risk of neoplasia – lymphosarcoma??

• Dermal Abrasion

• Based on observation of re-growth of hair at sites of full thickness skin trauma (skin biopsies and incision sites)

• Use of a dish washing “Scotch Pad”