Overview of endocrine skin diseases (Proceedings)

Thyroid Disease

Thyroid hormone is necessary to initiate the anagen phase of hair growth and all hair follicles, except those on the head and distal limbs, appear to be under its influence. The hairs on the head and distal limbs probably are also under its influence but the hair cycle in those areas is very different then elsewhere so the influence of thyroid hormones is less apparent. Deficiency can cause hair loss while excess appears to have little impact on hair growth, at least within a reasonable period of time. Some investigators believe that hypothyroidism does not cause hair loss in dogs (at least laboratory beagles) so hair follicle sensitivity to thyroid hormones may vary with species and breed. In the "generic" hypothyroid animal, hairs already in anagen will continue to grow but telogen hairs are not replaced. The first noticed hair loss will be incomplete (hypotrichosis v.s. alopecia) and occurs in frictional areas (tail, legs, ventrum). With time, the hair loss becomes more widespread and complete. If the "generic" dog goes through two hair cycles/year, hypothyroidism would be expected to result in widespread truncal hair loss in the first year of disease. If the mature animal presents for focal (e.g., flank alopecia), noninflammatory hair loss of 12 months or more duration, it is "impossible" for the hair loss to be due solely to hypothyroidism. The hypothyroid dog should have more widespread hair loss. If the thyroid tests in this dog are abnormal, the results are either spurious or the dog has some other endocrine/metabolic disease. Follicular dysplasias must be considered in young adult dogs.

Adrenal Disease

Adrenocortical hormones (glucocorticoids or sex steroids) can impact the hair coat but there is great species variability in response to "disease" levels of these hormones. For example, naturally-occurring glucocorticoid excess in dogs results in truncal hypotrichosis-to-alopecia while horses become hairy and cats have a "normal" hair coat. With the low incidence of adrenal disease in the cat and horse, only dogs are considered below.

      Glucocorticoid-predominating Adrenal Disease

Classical Cushing's disease is considered here and it is typically due to adrenal hyperplasia. In the classical case in the dog, constitutional signs, e.g., polyuria, polydypsia, polyphagia, are noticeable (may go unrecognized however) months before hair loss is recognized. Coat changes will be present weeks-to-months before the hair loss. Corticosteroids are catabolic hormones and impact hair growth, epidermal turnover, and sebaceous gland function. Early in the course of disease, the coat becomes dull, dry, and flaky and hair growth is slowed. The deceased growth rate only impacts anagen hairs and usually goes unnoticed in most dogs. Owners of show dogs or dogs who required regular grooming, e.g. poodles, may notice these early coat changes. With time, the telogen hairs on the body are lost and their replacement is very slow. With advanced disease, the classical dog has a truncal hypotrichosis with near complete alopecia in frictional areas. Complete truncal alopecia is extremely rare as the constitutional signs would be impossible for the owner to ignore.

      Sex Hormone-predominating Adrenal Disease

The adrenal cortex produces both glucocorticoid and sex steroid hormones. In dogs with bilateral adrenal hyperplasia, sex hormone levels often are elevated but usually have no impact on the skin changes seen. With adrenal neoplasia or the adrenal hyperplasia-like syndrome, sex hormone predominating skin change are visible.

      Adrenal Neoplasia

With a slow growing adrenal adenoma, the constitutional and cutaneous signs of Cushing's disease can mimic those seen with adrenal hyperplasia. With a rapidly growing adenoma or an adenocarcinoma, the clinical course and cutaneous signs usually are different. Constitutional signs and coat changes often are recognized simultaneously and the coat changes mimic those seen in gonadal sex hormone imbalance. Skin and coat changes seen include numerous comedones, coat color change, loss of primary but retention of secondary hairs on the trunk, and a patterned (focal and persistent) alopecia. The nature of the patterned hair loss depends on the animal's gender and the hormone in excess Females tend to develop flank and saddle hair loss while males have hair loss in the collar region, thighs, and ventrum.

      Adrenal Hyperplasia-like Syndrome (Alopecia X)

The syndrome is well documented in the Pomeranian where there is an adrenal 21-hydroxylase enzymatic deficiency which results in excess or inappropriate adrenal sex hormone production. The disease is recognized in many other breeds including the Chow Chow, Samoyed, and Keeshond. There is a remarkable breed overlap with the breeds at risk for adult-onset growth hormone disease or gonadal imbalance of the intact male dog. The adrenal irregularity in these breeds (and others) probably contributes (entirely causal?) to the clinical disease in growth hormone deficiency and some gonadal sex hormone dermatoses.

The adrenal hyperplasia-like syndrome is seen in young adult dogs of either sex. Most dogs are neutered but the hair loss will occur in intact animals and does not improve with neutering. The presentation for hair loss may not occur until the dog is middle-aged or old but coat irregularities will have been present for years if pictures of the dog are examined. At presentation, there are no constitutional signs of illness. Skin changes seen include numerous comedones, coat color change, loss of primary but retention of secondary hairs, and a patterned baldness of the collar region, thighs, perineum, and ventrum. With advancing time, the entire trunk is involved but there is significant retention of secondary hairs, giving the dog a puppy-like coat. Since glucocorticoid production is also impacted in these dogs, they eventually show clinical (polyuria, polydypsia, polyphagia) and some laboratory (slightly elevated SAP) evidence of classical adrenocorticism. Some dogs, especially Samoyeds, are very polyuric and polydipsic because they develop diabetes mellitus. Since these constitutional signs occur well after the coat changes, adrenal neoplasia can easily be dismissed.

All routine laboratory tests (hemogram, chemistry profile, urinalysis) are typically normal. Skin biopsy results will show an atrophic dermatitis with frequent catagenization of hair follicle (flame follicles) but these findings are not specific for this condition. Diagnosis is made via stimulation tests where sex hormones (cortisol) are determined pre- and post-ACTH administration. Since gonadal sex hormones influence the interpretation of this testing and the clinical signs of gonadal sex hormone imbalance mimic those seen herein, most intact animals are neutered before the testing is performed. If there is no hair regrowth within 3 months of the surgery, adrenal testing is indicated.

Some dogs will regrow coat with the administration of melatonin (0.5 mg/kg PO q12h for a minimum of 12 weeks). Since this hormone probably only is changing hair follicle receptor sensitivity , control will be lost sometime in the future and the hair loss will return. For these dogs and those that did not respond to it, the only other effective treatment involves the use of op-DDD (15-25 mg/kg q24h to load then once to twice weekly). Because of the expense and risk of this treatment, some owners will elect no treatment. These animals, especially when progestational irregularities are present, should be monitored for signs of diabetes mellitus. If the animal's sugar levels are rising, insulin-resistant diabetes, secondary to growth hormone induction by the progestagins, is likely.

Gonadal Sex Hormone Disorders

In normal animals, the gonadal sex hormones appear to have little impact on the skin. The female's coat doesn't change with estrus and neutered animals usually have perfectly normal coats. If neutering is associated with coat change, the animal may have some unrecognized adrenal disorder or other metabolic disease. In humans, the topographic and gender variability of sex hormone receptors (number and/or hormone affinity) is well known. Studies on the same are very limited in animals but patterns of hair loss seen in the gonadal sex hormone imbalances suggest similar variability in animals. The estrogenic zones in the female include the postauricular regions, flanks, perineum, and caudal ventrum. In males, the collar region, rump, perineum, and caudal ventrum are involved. The androgenic zones in both males and females include the collar area, rump, perineum, and ventrum. Clearly, there is overlap in the distribution which may be due to receptor similarities. Another explanation for the overlap involves the counter effects of one sex hormone for another. For example, progesterone is a profound antiandrogen. Accordingly, a bitch with a hyperprogesteronal problem will show androgenic coat changes.

      Gonadal Disorders of the Neutered Female

Hair loss associated with neutering is very rare. If seen, the short-coated animal will develop a postauricular, ventral, and perineal hypotrichosis-to-alopecic. Long coated dogs show loss of primary but retention of secondary truncal hairs and hair loss in the flank regions. Before a neutering-associated hair loss is considered, the history and dog's coat from puppyhood must be examined. A dog with a neutering-associated hair loss will have had a breed standard puppy coat which will develop to a normal breed standard coat as the pup ages. This coat is kept for varying periods of time before the hair loss starts. Most dogs who are thought to have an "estrogen-responsive" hair loss don't have this history. Their puppy coat is normal but their adult coat is sparser then breed standard and this abnormal coat is what is lost. Some lines within certain breeds, e.g., dachshund, Boston terrier, have sparse hair coats in the estrogen zones which the owner will consider normal. It may be normal for that line of dogs but it is not breed standard and indicates that the dog (line?) has a patterned baldness (regionalized follicular hypotrichosis).

      Gonadal Disorders of the Intact Female

Three different conditions are recognized. Dogs with ovarian dysregulation, ovarian cysts, or ovarian neoplasia often show cutaneous and constitutional signs of hyperestrogenism. They are in constant estrus, have numerous comedones on the vulvar and ventral skin, and have flank, perineal, and caudal ventrum hypotrichosis-to-alopecia. If the cyst or tumor produces progesterone rather then estrogen, signs of acromegaly are present.A more common condition occurs in the older, regularly cycling bitch. Some of these dogs will develop an androgen patterned hair loss (collar region, rump, perineum, ventrum). This hair loss is associated with signs of overt pseudocyesis. When the pseudocyesis is over, the hair will regrow spontaneously but a relapse can be expected at next estrus.The rarest condition involves the old dog who is completely anestral and has significant truncal hypotrichosis-to-alopecia. The hypogonadism in the dog is likely secondary to some other endocrine (hypothyroidism, hyperadrenocorticism) disorder and the dog should have a complete evaluation. If no other disease is found, neutering probably will result in hair regrowth.

      Gonadal Disorders of the Neutered Male

Very rare. If it exists, the dog should be middle-aged to old. Aside from truncal hair loss the remaining coat should be dull, dry, and flaky and the coat color should be changing.

      Gonadal Disorders of the Intact Male

Four different conditions are recognized. The first is associated with testicular neoplasia. Sertoli cell tumors and seminomas can produce estrogens while interstitial cell tumors can produce androgens. With estrogen producing tumors, hair loss occurs in the collar region, rump, perineum, and caudal ventrum and the coat often changes color. Nipple enlargement, a pendulous prepuce, and comedones usually are also seen. Some dogs develop a linear prepucial pigmentary change (erythematous or hyperpigmented) which extends from the prepucial orifice to the scrotum. With a functional interstitial cell tumor, the hair coat usually is normal (may be a little greasy). One usually sees macular melanosis of the ventral abdomen and perineum, enlargement with alopecia of the tail gland, and perianal gland tumors.

The second and most common condition occurs in dogs who appear to have normal testes (palpation, ejaculation, etc). These dogs lose primary but retain secondary hairs on the trunk, can show a coat color change, and have alopecia of the collar region, thighs, and perineum. Exposed skin tends to hyperpigment quickly. These dogs look like those with the adrenal hyperplasia-like syndrome. Some regrow hair with castration, some respond to testosterone supplementation, some respond to castration and then testosterone when the hair loss starts to recur, and some do not respond to any sex hormone manipulation. The latter group are clearly dogs with the adrenal hyperplasia-like syndrome. Many (all?) of the remainder probably also have the disorder but the gonadal hormones probably obscure the disease. If that is true, control will be lost in the future and dog will need to be treated for adrenal hyperplasia-like syndrome.

The third and fourth conditions are very rare. Rarely one will see a dog with palpably normal testes who has a greasy coat with or without lesions of seborrheic dermatitis and is both physically and sexually aggressive. Testosterone levels are very elevated and the dog returns to normal with castration. The behavioral aspects can persist for a long time after castration and these dogs can be very dangerous to other dogs and people. In the last condition, the dog has a truncal hair loss and both testes are small and atrophic. The hypogonadism (and hair loss?) probably is due to some other endocrine disease so a full evaluation is indicated. If no disease is found, castration and testosterone supplementation is indicated.

Growth Hormone Disorders

Growth hormone is necessary for the growth and development of all organ systems. Its effects on hair appear to be modulated through other hormones as there appear to be no growth hormone receptors on hair follicles

      Pituitary Dwarfism

Rare disorder. Puppies appear normal during puppyhood but don't grow like litter mates and retain puppy coat. Often have other intercurrent endocrinopathies. Replacement therapy of these other endocrinopathies can keep the coat fairly good but it still will be puppy-like. Early growth hormone replacement should return the dog to normal.

      Adult-onset Growth Hormone-Responsive Alopecia

A disorder of uncertain and questioned pathogenesis. High frequency in the Pomeranian, Chow Chow, Keeshond, and Poodle. Onset of coat problems early in adulthood (1-3 years). Males over represented. Coat changes seen include coat color change, loss of primary but retention of secondary hairs, and hair loss in the collar region, thighs and ventrum. The alopecia becomes more complete and widespread with advancing time. Exposed skin hyperpigments quickly and markedly. Beyond the skin changes, the dogs are otherwise normal. Some dogs appear small in stature but are at the low end of the breed standard.

Affected individuals show minimal growth hormone response to the administration of xylazine and many regrow hair when growth hormone is administered. Since there are no specific growth hormone receptors in the skin, not all dogs respond to treatment, and there is a striking breed overlap with the adrenal hyperplasia-like syndrome, the growth hormone "deficiency" may just be part of the adrenal dysfunction. This is supported when the dog regrows hair with treatment of the adrenal disease.

      Acromegaly

Associated with growth hormone excess due to pituitary neoplasia (rare) or excessive progestational stimulation from ovarian cysts, ovarian tumors, or progestational treatments. Animals rarely develop hair loss. Physical abnormalities include enlargement of the facial bones (big head, widened interdental spaces), enlargement of the pedal bones (fat foot, digital intertrigo), thickening of the skin over the dorsum, and seborrhea (greasy in dogs, flaky in cats). Reason for presentation is not skin but seizure disorder or insulin-resistant diabetes mellitus.