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Abstract The purpose of this study was to determine if there are specific steroid hormone aberrations associated
with suspect endocrine alopecias in dogs in whom hypothyroidism and hyperadrenocorticism have been excluded.
Steroid hormone panels submitted to the UTCVM endocrinology laboratory over a 7.5-year period (783 samples)
from dogs with alopecia were reviewed. During this period, 276 dogs met the criteria for inclusion and were comprised of 54 different breeds. Approximately 73% of dogs had at least one baseline or post-ACTH stimulation
steroid hormone intermediate greater than the normal range. The most frequent hormone elevation noted was
for progesterone (57.6% of samples). When compared with normal dogs, oestradiol was significantly greater in
Keeshond dogs and progesterone was significantly greater in Pomeranian and Siberian Husky dogs. Not all individual dogs had hormone abnormalities. Chow Chow, Samoyed and Malamute dogs had the greatest percentage
of normal steroid hormone intermediates of the dogs in this study. Baseline cortisol concentrations were significantly correlated with progesterone, 17-hydroxyprogesterone (17-OHP) and androstenedione. Results of this
study suggest that the pathomechanism of the alopecia, at least for some breeds, may not relate to steroid hormone
intermediates and emphasizes the need for breed specific normals.
Keywords: adrenal hyperplasia-like syndrome, Alopecia X, dogs, 17-hydroxyprogesterone, progesterone, sex
hormones, steroid hormone intermediates.
INTRODUCTION
Symmetrical alopecia is a common problem in dogs.
When faced with this presentation, one considers
hypothyroidism, hyperadrenocorticism, sex hormone
abnormalities such as hyperestrogenism, and more
recently, adrenal hyperplasia-like syndrome.1,2 The
latter syndrome has gone by the names of hyposomatotropism, growth hormone responsive dermatosis,
pseudo-Cushings syndrome, castration responsive
dermatosis, biopsy responsive dermatosis and woolly
syndrome. Many dermatologists have begun referring
to this syndrome as Alopecia X.1 This condition is
seen most commonly in breeds such as Poodles, plushcoated dogs such as Pomeranians, Chow Chows,
Samoyeds and Keeshonds.1,2 The alopecia occurs in
young adult dogs and occurs equally in males and
females, intact or neutered. Clinical signs consist of
loss of guard hairs progressing to complete alopecia of
the neck, tail, caudodorsum, perineum, caudal thighs
and ultimately trunk. In addition to hair loss, the skin
may become intensely hyperpigmented.2 Although
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L. A. Frank et al.
RESULTS
Seven hundred and eighty-three samples were reviewed.
A total of 276 dogs met the criteria for inclusion (7
intact females, 32 intact males, 134 spayed females and
103 neutered males) and were comprised of 54 different
Base (%)
Oestradiol
34/276 (12.3)
Progesterone
122/276 (44.2)
17-OHP
49/276 (17.8)
DHEAS**
15/276 (5.4)
Androstenedione 49/276 (17.8)
Post (%)
Base or
Post (%)
93
Table 2. Median (25 75th percentile) baseline concentrations of cortisol (ng mL1) and steroid hormone intermediates (ng mL1)
Breed
Normal*
American Eskimo
Chow Chow
N
60
7
14
Cocker Spaniel
Siberian Husky
Keeshond
12
Malamute
Pomeranian
63
Poodle
15
Samoyed
Normal range*
Cortisol
a
12.5
(7.2 19.6)
49.9b
(23.6 92.2)
30.8
(12.3 54.3)
32.2
(27.9 44.2)
35.0
(21.8 61.0)
32.6
(13.2 50.9)
24.4
(18.2 35.5)
55.5b
(26.6 74.0)
65.3b
(33.6 83.8)
32.8
(15.8 56.3)
2.2 58.8
45.47
(38.35 56.64)
51.00
(40.88 65.63)
41.95a
(33.20 50.80)
49.60a
(43.13 53.23)
60.30
(38.88 62.85)
67.10b
(61.10 83.40)
44.15a
(30.45 47.60)
42.47a
(32.20 53.40)
43.90
(34.86 65.83)
47.65
(45.20 52.94)
29.00 69.60
Progesterone
a
0.04
(0.02 0.08)
0.19
(0.10 0.52)
0.17
(0.04 0.35)
0.22
(0.08 0.29)
0.22b
(0.17 0.32)
0.23
(0.10 0.36)
0.07
(0.05 0.11)
0.31b
(0.10 0.61)
0.21
(0.07 0.44)
0.16
(0.03 0.30)
0.01 0.19
17-OHP
0.10
(0.06 0.20)
0.16
(0.07 0.44)
0.07
(0.04 0.10)
0.15
(0.05 0.25)
0.06
(0.03 0.10)
0.13
(0.07 0.26)
0.05a
(0.02 0.07)
0.19
(0.10 0.35)
0.27b
(0.16 0.43)
0.06
(0.02 0.19)
0.03 0.37
DHEAS
a
4.2
(3.11 6.63)
2.91
(2.04 3.74)
1.67b
(1.04 2.18)
6.52a,c
(5.3014.58)
2.60
(1.50 4.27)
3.87
(3.52 6.16)
2.60
(1.97 5.32)
2.04
(1.43 3.35)
2.00
(1.69 2.42)
3.45
(2.14 5.70)
2.00 15.91
Androstenedione
2.25
(1.30 3.15)
1.58
(1.23 2.11)
1.74
(0.61 4.28)
1.89
(1.08 3.06)
1.80
(1.67 7.35)
1.46
(1.01 2.25)
1.59
(1.23 3.94)
2.93
(1.55 7.20)
2.77
(1.56 9.73)
2.47
(1.31 3.86)
0.70 5.85
*Normal values determined on 30 spayed female and 30 neutered male dogs of various breeds and ages. 5
a,b,c
Differing letters indicate significant difference P < 0.05.
Table 3. Median (2575th percentile) post-ACTH stimulation concentrations of cortisol (ng mL 1) and steroid hormone intermediates (ng mL1)
Breed
Cortisol
Progesterone
17-OHP
DHEAS
Androstenedione
Normal*
60
101.4
(84.9 116.9)
135.0
(115.4 149.5)
111.0
(87.7 137.0)
71.1
(50.9 124.8)
74.4a
(73.3 94.5)
111.5
(83.2 159.1)
130.1
(97.6 141.0)
136.6b
(112.7 161.5)
136.0
(111.4 156.7)
111.2
(100.5 163.7)
70.55 167.50
45.44
(37.05 54.06)
46.3
(35.58 63.85)
33.45a
(28.20 42.70)
45.90
(41.95 51.70)
50.70
(42.73 63.90)
62.20
(59.60 78.90)
42.30
(31.85 48.95)
39.50
(31.20 49.50)
38.30
(29.85 53.65)
48.50
(38.25 54.41)
25.70 69.20
0.86
(0.59 1.13)
1.40
(1.05 2.59)
1.48
(0.73 1.75)
0.90
(0.56 1.20)
0.66
(0.55 1.16)
1.00
(0.55 2.24)
1.08
(0.44 1.51)
1.85a
(1.09 2.47)
2.10
(0.94 2.53)
0.61b
(0.35 1.02)
0.31 1.48
1.03
(0.68 1.28)
1.10
(0.55 2.61)
0.65
(0.43 0.96)
0.79
(0.59 1.13)
0.30a
(0.17 0.39)
0.77
(0.53 2.29)
0.55
(0.34 1.18)
1.25b
(0.87 2.00)
1.42b
(0.65 2.08)
0.39
(0.18 1.03)
0.32 2.76
7.74
(5.18 9.97)
4.63
(2.72 7.55)
2.74
(2.37 3.23)
7.90
(5.63 15.02)
2.54
(1.55 3.45)
6.63
( 4.52 9.26)
4.03
(3.15 7.83)
3.25
(2.50 5.01)
2.80
(2.23 4.18)
4.35
(3.29 6.39)
3.50 18.64
13.00
(10.20 22.85)
3.1
(1.52 3.39)
4.92
(1.14 12.00)
3.11
(2.71 5.65)
8.50
(3.25 9.96)
2.54
(1.79 3.26)
3.19
(1.73 12.01)
6.49
(2.89 17.10)
7.60
(1.88 19.73)
3.11
(1.47 5.57)
5.90 47.60
American Eskimo
Chow Chow
7
14
Cocker Spaniel
Siberian Husky
Keeshond
12
Malamute
Pomeranian
63
Poodle
15
Samoyed
Normal range*
*Normal values determined on 30 spayed female and 30 neutered male dogs of various breeds and ages. 5
a,b,c
Differing letters indicate significant difference P < 0.05.
94
L. A. Frank et al.
DISCUSSION
The most common causes of symmetrical alopecia in
dogs are endocrinopathies, with hypothyroidism and
hyperadrenocorticism being most frequent.1 Other
endocrine causes of symmetrical alopecia include sexhormone and adrenal imbalances.7,8 The mechanism
of the alopecia for all of these conditions is thought to
relate to the effect of hormones on the hair follicle,
inhibiting the normal cyclic pattern of hair growth.1
Adrenal hyperplasia-like syndrome (Alopecia X)
occurs frequently in young adult Poodles and plushcoated breeds.1,2 Eight breeds represented by at least
seven dogs in our study met these criteria and included
American Eskimo, Chow Chow, Siberian Husky, Keeshond, Malamute, Pomeranian, Poodle and Samoyed.
The surprise breed was the Cocker Spaniel, which is
not a breed in which this condition is typically seen.
Interestingly, the median age of the Cocker Spaniel
dogs was 9 years, greater than that seen for the other
breeds. The reason for this breeds representation is
unexplained.
The alopecia associated with adrenal hyperplasialike syndrome has been classified as an endocrine
alopecia,1 although the exact pathomechanism of the
alopecia is uncertain. Schmeitzel & Lothrop3 first
proposed the relationship of the bilateral alopecia and
hyperpigmentation in Pomeranians to an adrenal sex
hormone imbalance. Seven abnormal and 12 normal
intact Pomeranians were evaluated. Both abnormal
and normal dogs had abnormal adrenal steroid
intermediates and sex hormone concentrations compared with 19 mixed-breed dogs. Most notable was the
elevation of 17-OHP in these dogs. The authors theorized that there may be a partial deficiency of the
21-hydroxylase enzyme, as described in people with
congenital adrenal hyperplasia, that may account for the
laboratory and clinical findings. This increase in
17-OHP would provide more substrate for the formation of androstenedione and subsequently, oestradiol.
In people with late-onset congenital adrenal hyperplasia, clinical signs are associated with hyperandrogenism and may include premature development of pubic
hair in children, hirsutism in women, early fusion of
epiphyseal growth plates and severe cystic acne.9 In
addition, male-pattern baldness may be the sole presenting symptom in young women.9 This latter presentation has been theorized to be what is occurring in
these Pomeranians; however, testosterone is seldom
elevated in these dogs.6 Diagnosis in people is based
on increases of 17-OHP concentration post-ACTH
stimulation.9,10
The pattern of sex hormone and steroid hormone
intermediate elevations as described by Schmeitzel &
Lothrop3 is similar to our findings in Pomeranians and
Poodles as a group, with both breeds having elevated
mean baseline and post-stimulation progesterone and
17-OHP. A similar hormone pattern was also noted
with American Eskimo and Keeshond dogs. Only
Pomeranians and Siberian Huskies, however, had significantly greater baseline progesterone than normal
dogs and only Poodles had significantly greater baseline
17-OHP than Malamutes. Post-stimulation progesterone was only significantly greater in Pomeranians than
in Samoyeds and post-stimulation 17-OHP was only
significantly greater in Pomeranians and Poodles when
compared with Siberian Huskies. It is important to
note that lack of statistical differences may reflect the
small numbers of dogs representing certain breeds and
not a true lack of significant difference. The characteristic elevation of post-ACTH stimulation 17-OHP, as
described in Pomeranians with adrenal hyperplasialike syndrome, was not seen in any Chow Chows,
Cocker Spaniels, Siberian Huskies, Malamutes or
Samoyeds. Baseline 17-OHP was increased in one dog
from each of Chow Chow, Cocker Spaniel and Malamute breed groups. In fact, baseline or post-stimulation
17-OHP was only increased in 20.7% of the dogs, with
the majority of increases (17.8%) occurring in baseline
samples.
The most common abnormality noted in our study
was increased baseline and/or post-stimulation progesterone. Over 57% of the dogs had progesterone concentrations outside the normal range (36% had increased
post-stimulation progesterone). The action of progesterone on hair growth has not been defined. Hyperprogesteronemia was associated with alopecia in a dog
with Sertoli cell tumour.11 Progesterone has been
shown to bind to the glucocorticoid receptor in the
dog,12 and glucocorticoids can block hair growth,13
suggesting one mechanism of the alopecia. In addition,
progesterone can cross-react with the testosterone
receptor.14 The net affect could be either androgenic or
anti-androgenic. Hyperandrogenism has been uncommonly associated with alopecia in dogs1,8 and has been
shown to delay initiation of hair growth in mice.15 In
people, androgenic alopecia is a result of a decrease in
the duration of the anagen phase and progressive
95
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3. Schmeitzel, L.P., Lothrop, C.D. Hormonal abnormalities in Pomeranians with normal coat and in Pomeranians with growth hormone-responsive dermatosis.
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4. Ashley, P.F., Frank, L.A., Schmeitzel, L.P. et al. Effect of
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Fadok, V.A., Lothrop, C.D., Coulson, P. Hyperprogesteronemia associated with Sertoli cell tumor and alopecia
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Rsum Le but de cette tude est de dterminer si des anomalies des hormones strodes existent dans les
alopcies dorigine endocrinienne, hormis lhyperadrnocorticisme et lhypothyrodie. Les dosages dhormones
strodiennes soumis aux laboratoire dendocrinologie de lUTCVM sur une priode de 7.5 ans (783 prlvements) provenant de chiens souffrant dalopcie ont t analyss. Durant cette priode, 276 chiens de 54 races
diffrentes prsentaient les critres dinclusion. Environ 73% des chiens avaient au moins un dosage avant ou aprs
stimulation au dessus des normes. Llvation la plus frquente a t note pour la progestrone (57.6% des
prlvements). En comparaison des chiens normaux, lestradiol tait significativement plus lev chez le keeshond
et la progestrone chez les pomeranians et les siberain husky. Tous les chiens ne prsentaient pas ncessairement
danomalie. Les Chow chow, les Samoyede et les Malamute taient les races avec le moins danomalie. Les taux
de cortisol basal taient significativement corrls avec la progestrone, la 17-hydroxyprogesterone (17-OHP),
et landrostenedione. Les rsultats de cette tude suggrent que le mcanisme pathognique de lalopcie, au
moins pour certaines races, nest pas relie un trouble des hormones stroidiennes, et prcise la ncessit davoir
des normes par race.
97
Resumen El objetivo de este estudio fue determinar si existen alteraciones especficas de las hormonas esteroideas asociadas con alopecias endocrinas tras haber excluido un hipotiroidismo y un hiperadrenocorticismo. Se
revisaron perfiles de hormonas esteroideas de perros con alopecia solicitados al laboratorio de endocrinologa
del UTCVM, en un perodo de 7.5 aos (783 muestras). Durante este perodo, 276 perros cumplieron los criterios
de inclusin en el estudio y englobaron 54 razas diferentes. Aproximadamente, un 73% de los perros tenan al
menos un nivel de hormonas esteroideas intermediarias basal o post estimulacin con ACTH superior al rango
normal. La elevacin de hormona ms frecuente fue la progesterona (57.6% de las muestras). Cuando los valores
fueron comparados con perros normales, los niveles de estradiol fueron superiores en perros keeshond y los de
progesterona en pomeranian y Siberian husky. No todos los perros tenan anormalidades hormonales. De todos
los perros en el estudio, los de raza chow chow, samoyedo y malamute presentaron el porcentaje mayor de niveles
normales de hormonas esteroideas intermediarias. Las concentraciones basales de cortisol estuvieron correlacionadas significativamente con la progesterona, 17-hidroxiprogesterona (17-OHP), y androstenediona. Los
resultados de este estudio sugieren que los mecanismos o patognesis de la alopecia, al menos en algunas razas,
pueden no estar relacionados con los intermediarios de las hormonas esteroideas y enfatiza la necesidad de
conocer los valores especficos normales para cada raza.
Zusammenfassung Das Ziel dieser Studie war die Bestimmung von mit vermutlichen hormonellen Erkrankungen
einhergehenden Steroidhormonabnormalitten bei Hunden, bei denen Hypothyreose oder Hyperadrenokortizismus ausgeschlossen worden war. ber einen Zeitraum von 7.5 Jahren wurden beim UTCVM Hormonlaboratorium eingereichte Steroidhormonanalysen von Hunden mit Alopezie berprft. In diesem Zeitraum
entsprachen 276 Hunde von 54 verschiedenen Rassen den Einschlusskriterien. Ungefhr 73% aller Hunde hatten
zumindest einen Basis- oder Post-ACTH-Stimulationswert von einem Steroidzwischenprodukt ber den
Normalwerten. Die hufigste Erhhung eines Hormons wurde bei Progesteron festgestellt (57.6% der Proben).
Verglichen mit normalen Hunden war stradiol beim Keeshond und Progesteron beim Pomeraner und
Sibirischem Husky signifikant erhht. Nicht alle Hunde hatten Hormonabnormalitten. Chow Chow, Samoyede
und Malamut hatten die grsste Anzahl von normalen Steroidzwischenprodukten aller Hunde in dieser Studie.
Kortisolbasiswerte waren signifikant mit Progesteron, 17-hydroxyprogesteron (17-OHP) und Androstenedion
korreliert. Die Ergebnisse dieser Studie deuten darauf hin, dass die Pathogenese der Alopezie, zumindest fr
einige Rassen, nicht unbedingt mit Steroidzwischenprodukten in Verbindung steht und betont den Bedarf an
rassenspezifischen Normalwerten.