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Advances in Clinical Dermatology
+
.20
Sex Hormone-Related and Growth Hormone-Related Alopecias Lynn P. Schmeitzel, DVM*
Canine endocrine dermatoses are characterized by bilateral symmetrical alopecia. Hyperadrenocorticism and hypothyroidism are common causes of endocrine-related alopecia in dogs; whereas sex hormone imbalances and growth hormone deficiency are relatively rare causes of alopecia in dogs. Although they are uncommon, there is continued interest in sex and growth hormone-related dermatoses and several new syndromes associated with these hormones have recently heen described. GROWTH HORMONE Growth Hormone Physiology Growth hormone, also called somatotropin, is a polypeptide secreted by the adenohypophysis. 13· 52 Immunohistochemical techniques show that cells. producing growth hormone, called somatotrophs, make up almost half the bulk of the anterior pituitary. 76 Somatotrophs and mammotrophs (prolactin secreting cells) represent the acidophils in the anterior pituitary observed with light microscopy. 76 Growth hormone acts either directly on the target tissues or indirectly via intermediary hormones called somatomedins (Fig. 1). 8 • 13 • 20• 22 • 23 • 52• 69 Somatomedins are peptides presumably secreted by the liver in response to growth hormone stimulation. 13• 20· 23 • 69 Growth hormone has both catabolic and anabolic effects. 8 • 13• 52• 69 • 75 The catabolic effects of growth hormone include increased lipolysis; fatty acid oxidation, and restricted glucose transport. 8• 13 • 52 • 75 The effects of growth hormone on glucose transport cause elevated blood glucose concentration. 13 The anabolic effects of growth hormone include increased amino acid transport; decreased amino acid catabolism; and stimulation of hepatic DNA, RNA, and protein synthesis. 8 · 13 Additionally, growth hormone *Diplomate, American College of Veterinary Dermatology; and Associate Professor, Dermatology, Department of Urban Practice, University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee Veterinary Clinics of North America: Small Animal Practice-Val. 20, No. 6, November 1990
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Anterior Pituitary
GH------, b
Somatomedin Producing Cell
Figure 1. Mechanisms of action of growth hormone. Path a: Growth hormone (GH) released from the anterior pituitary acts indirectly on tissues by inducing another cell to produce the intermediary hormones called somatomedins (SM[s]). Path b: Growth hormone also acts directlv on the target cell. Path c: Somatomedins then exert effects on the target cell.
SM[s]
stimulates the production of somatomedins, also called insuJinlike growth factors, that have growth-promoting effects on muscle and bone. 71 • 75 The net effect of growth hormone and somatomedins is anabolic. 75 The effects of growth hormone on the ,?kin are apparently directly mediated by the hormone and indirectly mediated by somatomedins. 23 Growth hormone is necessary for hair growth and the development of elastin fibers in the skin. 23 • 64 • 79 · Growth hormone deficiency causes typical endocrine-induced cutaneous changes in the skin such as hyperkeratosis, epidermal atrophy, epidermal melanosis, follicular atrophy and keratosis, telogenization of hair follicles, sebaceous gland atrophy, and dermal thinning. 52 • 64 In addition , depletion of dermal elastin fibers may be observed. 52 · 64 Growth hormone secretion is episodic and primarily under the control of two hypothalamic hormones, growth hormone-releasing factor, which stimulates growth hormone release, and somatostatin, which inhibits growth hormone release. 13 In addition, growth hormone secretion can be enhanced or inhibited by numerous neurogenic, metabolic, and hormonal factors (Table 1). 13 · 38• 65• 74 Growth Hormone and Sex Hormone Interactions Interestingly, there is an association between the steroidal sex hormones and growth hormone. Both growth hormone and testosterone synergistically influence growth. In humans, testosterone has very poor growth-stimulating effect in the absence of growth hormone . 79 Additionally, the androge nic effects of testosterone are modified by growth hormone. In humans, the appearance of axillary hair, a secondary sex characteristic induced by androgenic hormone stimulation, is absent or delayed in growth
SEX HORMONE-RELATED AND GROWTH HORMONE-RELATED ALOPECIAS
1581
Table 1. Factors Irifluencing Normal Growth Hormone Secretion GROWTH HORMONE (GH) SECRETION
Augmented
Inhibited
Neurogenic Stages III and IV sleep Stress (traumatic, surgical, infectious, psychogenic) a-Adrenergic agonists 13-Adrenergic antagonists L-Dopa
REM sleep Emotional deprivation 13-Adrenergic agonists a-Adrenergic antagonists
Metabolic
Hypoglycemia (fasting) Falling fatty acid level Amino acids Uncontrolled diabetes Uremia Hepatic cirrhosis
Hyperglycemia Rising fatty acid level Obesity
Hormonal
Growth hormone-releasing factor Low somatomedin (?) Estrogens Androgens Progesterone (basal levels of GH increase) Glucagon Vasopressin
Somatostatin Hypothyroidism Large doses of corticosteroids Androgen deficiency Medroxyprogesterone acetate (reduced growth hormone response to clonidine)
Adapted from Daughaday WH: The anterior pituitary. In Wilson JD, Foster DW (eds): William's Textbook of Endocrinology, ed 7. Philadelphia, WB Saunders, 1983.
hormone-deficient individuals. 79 Growth hormone supplementation reduces the dose of testosterone and the time required for axillary hair to develop in these individuals. 79 Sex hormones have both stimulating and inhibitory effects on growth hormone secretion. In general, sex hormones stimulate growth hormone secretion. 68 • 75 Estrogens and testosterone increase growth hormone response to provocative stimuli in humans. 71 In rats, testosterone augments growth hormone response to a-agonists and growth hormone-releasing factor. 38• 74 In dogs, medroxyprogesterone acetate elevated basal growth hormone levels and induced nonsuppressibility of growth hormone concentrations during an intravenous glucose load in dogs. 28 The effects of testosterone on canine growth hormone secretion are unknown. Conversely, sex hormones may inhibit growth hormone secretion. In humans, progestogens inhibited growth hormone responsiveness to provocative stimuli. 59 In dogs, the administration of the progestational compound medroxyprogesterone acetate (MPA) 1n combination with estradiol also reduced growth hormone response to clonidine. 59 The suppression was probably mediated by MPA because estradiol supplementation alone had no effect on basal growth hormone levels or on growth hormone response to clonidine. 59 Growth Hormone Function Tests Canine growth hormone concentration is measured in plasma or serum by homologous radioimmunoassay (RIA). 42 • 52 This test is available only on
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a very limited basis. Basal growth hormone concentrations in normal dogs are low, 1.0 to 4.5 ng/mL, making the measurement of basal growth hormone concentration inadequate to diagnose growth hormone deficiency. 42 • 52 Therefore, a growth hormone response test using the aadrenergic agonists clonidine HCl (10 f.Lg/kg IV) or xylazine hydrochloride (100 to 300 f.Lg/kg IV) is the preferred test to evaluate growth hormone secretion. 35 • 42 • 52 These a-adrenergic agonists stimulate the endogenous release of growth hormone-releasing factor from the hypothalamus that subsequently induces growth hormone release from the adenohypophysis. 42 The author recommends using xylazine HCl (Rompun, Haver, Shawnee, KS) because it is readily available in many veterinary practices. Two to four milliliters of blood are collected before and 15, 30, 45, and 60 minutes after the administration of xylazine HCl, clonidine HCl, or human growth hormone-releasing factor. 35 • 42 • 52 The blood should be centrifuged and the plasma or serum kept frozen at - 20°C until it is assayed. 42 Peak levels of growth hormone occur at 30 minutes. 35 At the University of Tennessee, normal canine mean-peak serum growth hormone concentration is 43.5 ± 40.8 ng/mL at 15 minutes after xylazine HCl administration. 61 Clonidine HCl and xylazine HCl are potent hypotensive agents. Side effects may include drowsiness, bradycardia, and collapse. These effects may last up to 1 hour. Atropine may be used to reverse the bradycardia, and yohimbine or phentolamine (both a-adrenergic "!;ntagonists) may be used to reverse the hypotension. 42 Yohimbine (Yobine, Lloyd Laborato:r;ies, Shenandoah, lA) is commercially available now for use in dogs. The dose is 0.11 mg/kg IV. 72 At the University o( Tennessee, a majority of dogs tested (including toy breeds) tolerated 300 f,Lglkg of xylazine IV quite well and seldom required therapy with atropine or a-adrenergic antagonists. However, severe hypotension and shock have been reported in small breeds that were given this dose of xylazine. 52 No adverse side effects have been observed after administration of human growth hormone-releasing factor to dogs. 42 • 61 Human growth hormone-releasing factor is not commercially available. The absence of a significant increase in growth hormone concentration in the plasma or serum after stimulation is consistent with a diagnosis of growth hormone deficiency (hyposomatotropism). However, before a diagnosis of hyposomatotropism can be made, hypothyroidism, hyperadrenocorticism, and sex hormone imbalances should be ruled out with appropriate tests because these disorders may inhibit the endogenous release of growth hormone in dogs given a-adrenergic agonists. 22 • 42 • 47• 54 Somatomedins may also be measured by RIA. 42 This test is available only in certain research laboratories. 20 • 42 Somatomedin C, insulinlike growth factor I, is most often measured. 21 • 25• 26 • 42 Somatomedin levels would be expected to be extremely low or undetectable in growth hormone-deficient states. 52 However, somatomedin C levels must be interpreted according to the size of the breed tested because somatomedin C levels parallel body size. 25 • 26 Lower concentrations of somatomedin C have been detected in normal dogs of small breeds, whereas normal dogs of larger breeds have significantly higher levels. 25• 26
SEX HORMONE- RELATED AND GROWTH HORMONE- RELATED ALOPECIAS
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Growth Hormone-Related Alopecias Two types of growth hormone-related endocrine alopecias occur in dogs, pituitary dwarfism and growth hormone-responsive alopecia. Pituitary dwarfism. Canine pituitary dwarfism is a hereditary hypopituitarism causing short stature, retention of puppy coat, bilateral symmetrical alopecia, and hyperpigmentation (Fig. 2). This condition is primarily reported in the German shepherd dog, although a variety of breeds may be affected. In German shepherds and carnelian bear dogs, pituitary dwarfism is inherited as an autosomal recessive trait. 3• 20• 52 Most affected dogs have a variably sized cyst of the Rathke's cleft.20• 52 Failure of the oropharyngeal ectoderm to differentiate into the growth hormone-producing cells of the adenohypophysis results in the cyst and growth hormone deficiency. In addition to hyposomatotropism, affected dogs may develop secondary hypothyroidism, hypoadrenocorticism, and gonadal abnormalities because of deficiencies of thyrotropin (TSH), adrenocorticotropin (ACTH), LH, and FSH. 8 · 19 • 52· 66 The affected dogs appear normal for the first few months of life. Later, the dogs fail to grow, and retention of the puppy coat (secondary hairs) with a loss of the guard hairs (primary hairs) is observed.8 • 19· 52 Then bilateral symmetrical alopecia with hyperpigmentation develops. Initially, the head
Figure 2. Pituitary dwarfism in a 1-year-old intact male German shepherd dog-wolf cross. This dog had both hyposomatotropism and hypothyroidism. There is generalized partial alopecia, with secondary (undercoat) hairs remaining. The kyphosis is caused by collapse of the vertebral growth plates.
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and distal extremities are often spared but hair loss may develop in these regions as well. Other clinical signs include delayed or absent permanent dentition, skeletal abnormalities caused by delayed physeal closure, atrophic testes, abnormal estrus cycles, and behavioral abnormalities. 52 Differential diagnoses include congenital hypothyroidism, malnutrition, and metabolic disorders. 8 • 52 Diagnosis of pituitary dwarfism is based on signalment, history, physical examination, radiography (to show skeletal abnormalities), skin biopsies, and endocrine function tests. 52 A complete blood count, serum chemistry panel, and urinalysis seldom reveal any abnormalities in pituitary dwarfism but may reveal other metabolic disorders causing dwarfism. 8 Microscopic evaluation of skin biopsies show changes consistent with an endocrinopathy including orthokeratotic hyperkeratosis; follicular keratosis, dilatation, and atropy; telogenization of hair follicles; sebaceous gland atrophy; epidermal melanosis; and a thin dermis. 52 • 64 Decreased amount and size of dermal elastin fibers, when present, is highly suggestive of hyposomatotropism. 52 • 64 In addition, vacuolated or hypertrophied arrector pili muscles may be present in cases with concurrent hypothyroidism. 52 • 64 A growth hormone-response test using xylazine HCl or clonidine HCl is necessary to document growth hormone deficiency. In addition, TSH and ACTH response tests should be performed to determine if secondary hypothyroidism or hypoadrenocorticism are also present. 8 · 52 Somatomedin levels also should be extremely low (< 5 ng/rnL) in affected dogs, although this test is available on a research basis only. 1• 21 · 52 Also the values need to be interpreted according to the size of the bret
Advances in Clinical Dermatology
+
.20
Sex Hormone-Related and Growth Hormone-Related Alopecias Lynn P. Schmeitzel, DVM*
Canine endocrine dermatoses are characterized by bilateral symmetrical alopecia. Hyperadrenocorticism and hypothyroidism are common causes of endocrine-related alopecia in dogs; whereas sex hormone imbalances and growth hormone deficiency are relatively rare causes of alopecia in dogs. Although they are uncommon, there is continued interest in sex and growth hormone-related dermatoses and several new syndromes associated with these hormones have recently heen described. GROWTH HORMONE Growth Hormone Physiology Growth hormone, also called somatotropin, is a polypeptide secreted by the adenohypophysis. 13· 52 Immunohistochemical techniques show that cells. producing growth hormone, called somatotrophs, make up almost half the bulk of the anterior pituitary. 76 Somatotrophs and mammotrophs (prolactin secreting cells) represent the acidophils in the anterior pituitary observed with light microscopy. 76 Growth hormone acts either directly on the target tissues or indirectly via intermediary hormones called somatomedins (Fig. 1). 8 • 13 • 20• 22 • 23 • 52• 69 Somatomedins are peptides presumably secreted by the liver in response to growth hormone stimulation. 13• 20· 23 • 69 Growth hormone has both catabolic and anabolic effects. 8 • 13• 52• 69 • 75 The catabolic effects of growth hormone include increased lipolysis; fatty acid oxidation, and restricted glucose transport. 8• 13 • 52 • 75 The effects of growth hormone on glucose transport cause elevated blood glucose concentration. 13 The anabolic effects of growth hormone include increased amino acid transport; decreased amino acid catabolism; and stimulation of hepatic DNA, RNA, and protein synthesis. 8 · 13 Additionally, growth hormone *Diplomate, American College of Veterinary Dermatology; and Associate Professor, Dermatology, Department of Urban Practice, University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee Veterinary Clinics of North America: Small Animal Practice-Val. 20, No. 6, November 1990
1579
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LYNN
P.
SCHMEITZEL
Anterior Pituitary
GH------, b
Somatomedin Producing Cell
Figure 1. Mechanisms of action of growth hormone. Path a: Growth hormone (GH) released from the anterior pituitary acts indirectly on tissues by inducing another cell to produce the intermediary hormones called somatomedins (SM[s]). Path b: Growth hormone also acts directlv on the target cell. Path c: Somatomedins then exert effects on the target cell.
SM[s]
stimulates the production of somatomedins, also called insuJinlike growth factors, that have growth-promoting effects on muscle and bone. 71 • 75 The net effect of growth hormone and somatomedins is anabolic. 75 The effects of growth hormone on the ,?kin are apparently directly mediated by the hormone and indirectly mediated by somatomedins. 23 Growth hormone is necessary for hair growth and the development of elastin fibers in the skin. 23 • 64 • 79 · Growth hormone deficiency causes typical endocrine-induced cutaneous changes in the skin such as hyperkeratosis, epidermal atrophy, epidermal melanosis, follicular atrophy and keratosis, telogenization of hair follicles, sebaceous gland atrophy, and dermal thinning. 52 • 64 In addition , depletion of dermal elastin fibers may be observed. 52 · 64 Growth hormone secretion is episodic and primarily under the control of two hypothalamic hormones, growth hormone-releasing factor, which stimulates growth hormone release, and somatostatin, which inhibits growth hormone release. 13 In addition, growth hormone secretion can be enhanced or inhibited by numerous neurogenic, metabolic, and hormonal factors (Table 1). 13 · 38• 65• 74 Growth Hormone and Sex Hormone Interactions Interestingly, there is an association between the steroidal sex hormones and growth hormone. Both growth hormone and testosterone synergistically influence growth. In humans, testosterone has very poor growth-stimulating effect in the absence of growth hormone . 79 Additionally, the androge nic effects of testosterone are modified by growth hormone. In humans, the appearance of axillary hair, a secondary sex characteristic induced by androgenic hormone stimulation, is absent or delayed in growth
SEX HORMONE-RELATED AND GROWTH HORMONE-RELATED ALOPECIAS
1581
Table 1. Factors Irifluencing Normal Growth Hormone Secretion GROWTH HORMONE (GH) SECRETION
Augmented
Inhibited
Neurogenic Stages III and IV sleep Stress (traumatic, surgical, infectious, psychogenic) a-Adrenergic agonists 13-Adrenergic antagonists L-Dopa
REM sleep Emotional deprivation 13-Adrenergic agonists a-Adrenergic antagonists
Metabolic
Hypoglycemia (fasting) Falling fatty acid level Amino acids Uncontrolled diabetes Uremia Hepatic cirrhosis
Hyperglycemia Rising fatty acid level Obesity
Hormonal
Growth hormone-releasing factor Low somatomedin (?) Estrogens Androgens Progesterone (basal levels of GH increase) Glucagon Vasopressin
Somatostatin Hypothyroidism Large doses of corticosteroids Androgen deficiency Medroxyprogesterone acetate (reduced growth hormone response to clonidine)
Adapted from Daughaday WH: The anterior pituitary. In Wilson JD, Foster DW (eds): William's Textbook of Endocrinology, ed 7. Philadelphia, WB Saunders, 1983.
hormone-deficient individuals. 79 Growth hormone supplementation reduces the dose of testosterone and the time required for axillary hair to develop in these individuals. 79 Sex hormones have both stimulating and inhibitory effects on growth hormone secretion. In general, sex hormones stimulate growth hormone secretion. 68 • 75 Estrogens and testosterone increase growth hormone response to provocative stimuli in humans. 71 In rats, testosterone augments growth hormone response to a-agonists and growth hormone-releasing factor. 38• 74 In dogs, medroxyprogesterone acetate elevated basal growth hormone levels and induced nonsuppressibility of growth hormone concentrations during an intravenous glucose load in dogs. 28 The effects of testosterone on canine growth hormone secretion are unknown. Conversely, sex hormones may inhibit growth hormone secretion. In humans, progestogens inhibited growth hormone responsiveness to provocative stimuli. 59 In dogs, the administration of the progestational compound medroxyprogesterone acetate (MPA) 1n combination with estradiol also reduced growth hormone response to clonidine. 59 The suppression was probably mediated by MPA because estradiol supplementation alone had no effect on basal growth hormone levels or on growth hormone response to clonidine. 59 Growth Hormone Function Tests Canine growth hormone concentration is measured in plasma or serum by homologous radioimmunoassay (RIA). 42 • 52 This test is available only on
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a very limited basis. Basal growth hormone concentrations in normal dogs are low, 1.0 to 4.5 ng/mL, making the measurement of basal growth hormone concentration inadequate to diagnose growth hormone deficiency. 42 • 52 Therefore, a growth hormone response test using the aadrenergic agonists clonidine HCl (10 f.Lg/kg IV) or xylazine hydrochloride (100 to 300 f.Lg/kg IV) is the preferred test to evaluate growth hormone secretion. 35 • 42 • 52 These a-adrenergic agonists stimulate the endogenous release of growth hormone-releasing factor from the hypothalamus that subsequently induces growth hormone release from the adenohypophysis. 42 The author recommends using xylazine HCl (Rompun, Haver, Shawnee, KS) because it is readily available in many veterinary practices. Two to four milliliters of blood are collected before and 15, 30, 45, and 60 minutes after the administration of xylazine HCl, clonidine HCl, or human growth hormone-releasing factor. 35 • 42 • 52 The blood should be centrifuged and the plasma or serum kept frozen at - 20°C until it is assayed. 42 Peak levels of growth hormone occur at 30 minutes. 35 At the University of Tennessee, normal canine mean-peak serum growth hormone concentration is 43.5 ± 40.8 ng/mL at 15 minutes after xylazine HCl administration. 61 Clonidine HCl and xylazine HCl are potent hypotensive agents. Side effects may include drowsiness, bradycardia, and collapse. These effects may last up to 1 hour. Atropine may be used to reverse the bradycardia, and yohimbine or phentolamine (both a-adrenergic "!;ntagonists) may be used to reverse the hypotension. 42 Yohimbine (Yobine, Lloyd Laborato:r;ies, Shenandoah, lA) is commercially available now for use in dogs. The dose is 0.11 mg/kg IV. 72 At the University o( Tennessee, a majority of dogs tested (including toy breeds) tolerated 300 f,Lglkg of xylazine IV quite well and seldom required therapy with atropine or a-adrenergic antagonists. However, severe hypotension and shock have been reported in small breeds that were given this dose of xylazine. 52 No adverse side effects have been observed after administration of human growth hormone-releasing factor to dogs. 42 • 61 Human growth hormone-releasing factor is not commercially available. The absence of a significant increase in growth hormone concentration in the plasma or serum after stimulation is consistent with a diagnosis of growth hormone deficiency (hyposomatotropism). However, before a diagnosis of hyposomatotropism can be made, hypothyroidism, hyperadrenocorticism, and sex hormone imbalances should be ruled out with appropriate tests because these disorders may inhibit the endogenous release of growth hormone in dogs given a-adrenergic agonists. 22 • 42 • 47• 54 Somatomedins may also be measured by RIA. 42 This test is available only in certain research laboratories. 20 • 42 Somatomedin C, insulinlike growth factor I, is most often measured. 21 • 25• 26 • 42 Somatomedin levels would be expected to be extremely low or undetectable in growth hormone-deficient states. 52 However, somatomedin C levels must be interpreted according to the size of the breed tested because somatomedin C levels parallel body size. 25 • 26 Lower concentrations of somatomedin C have been detected in normal dogs of small breeds, whereas normal dogs of larger breeds have significantly higher levels. 25• 26
SEX HORMONE- RELATED AND GROWTH HORMONE- RELATED ALOPECIAS
1583
Growth Hormone-Related Alopecias Two types of growth hormone-related endocrine alopecias occur in dogs, pituitary dwarfism and growth hormone-responsive alopecia. Pituitary dwarfism. Canine pituitary dwarfism is a hereditary hypopituitarism causing short stature, retention of puppy coat, bilateral symmetrical alopecia, and hyperpigmentation (Fig. 2). This condition is primarily reported in the German shepherd dog, although a variety of breeds may be affected. In German shepherds and carnelian bear dogs, pituitary dwarfism is inherited as an autosomal recessive trait. 3• 20• 52 Most affected dogs have a variably sized cyst of the Rathke's cleft.20• 52 Failure of the oropharyngeal ectoderm to differentiate into the growth hormone-producing cells of the adenohypophysis results in the cyst and growth hormone deficiency. In addition to hyposomatotropism, affected dogs may develop secondary hypothyroidism, hypoadrenocorticism, and gonadal abnormalities because of deficiencies of thyrotropin (TSH), adrenocorticotropin (ACTH), LH, and FSH. 8 · 19 • 52· 66 The affected dogs appear normal for the first few months of life. Later, the dogs fail to grow, and retention of the puppy coat (secondary hairs) with a loss of the guard hairs (primary hairs) is observed.8 • 19· 52 Then bilateral symmetrical alopecia with hyperpigmentation develops. Initially, the head
Figure 2. Pituitary dwarfism in a 1-year-old intact male German shepherd dog-wolf cross. This dog had both hyposomatotropism and hypothyroidism. There is generalized partial alopecia, with secondary (undercoat) hairs remaining. The kyphosis is caused by collapse of the vertebral growth plates.
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and distal extremities are often spared but hair loss may develop in these regions as well. Other clinical signs include delayed or absent permanent dentition, skeletal abnormalities caused by delayed physeal closure, atrophic testes, abnormal estrus cycles, and behavioral abnormalities. 52 Differential diagnoses include congenital hypothyroidism, malnutrition, and metabolic disorders. 8 • 52 Diagnosis of pituitary dwarfism is based on signalment, history, physical examination, radiography (to show skeletal abnormalities), skin biopsies, and endocrine function tests. 52 A complete blood count, serum chemistry panel, and urinalysis seldom reveal any abnormalities in pituitary dwarfism but may reveal other metabolic disorders causing dwarfism. 8 Microscopic evaluation of skin biopsies show changes consistent with an endocrinopathy including orthokeratotic hyperkeratosis; follicular keratosis, dilatation, and atropy; telogenization of hair follicles; sebaceous gland atrophy; epidermal melanosis; and a thin dermis. 52 • 64 Decreased amount and size of dermal elastin fibers, when present, is highly suggestive of hyposomatotropism. 52 • 64 In addition, vacuolated or hypertrophied arrector pili muscles may be present in cases with concurrent hypothyroidism. 52 • 64 A growth hormone-response test using xylazine HCl or clonidine HCl is necessary to document growth hormone deficiency. In addition, TSH and ACTH response tests should be performed to determine if secondary hypothyroidism or hypoadrenocorticism are also present. 8 · 52 Somatomedin levels also should be extremely low (< 5 ng/rnL) in affected dogs, although this test is available on a research basis only. 1• 21 · 52 Also the values need to be interpreted according to the size of the bret
