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Sex Hormone Dermatoses
World Small Animal Veterinary Association World Congress Proceedings, 2004
William H. Miller, Jr., VMD, DACVD
College of Veterinary Medicine, Cornell University
Ithaca, NY, USA
Ithaca, NY, USA
Domestic animals produce sex hormones in their
gonads and in their adrenal glands. As far as the skin is concerned,
there appears to be little need for the sex hormones. Neutered dogs and
cats rarely lose hair in association with the neutering. Even if the
neutered animal undergoes a bilateral adrenalectomy, postsurgical hair
loss is rare. Sex hormone excesses, e.g., estrogen excess associated
with a Sertoli cell tumor, or sex hormone imbalances, e.g., progesterone
treatments resulting in a hypo-androgenism condition, typically will
produce coat changes.
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 hypoprogesterone 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 hyper-pigment 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.
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 hyper-pigments 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.
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
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 progestagens, is likely.
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