J. small Anim. Pract. ( 1 978) 19,711-727.
Pituitary dwarfism in German Shepherd Dogs G. S . ALLAN*, C. R. R. H U X T A B L E t , C. R . HOWLETTS, R. C. BAXTERS, B. D U F F 7 A N D B. R. H . FARROW** *Kuringai Animal Hospital, New South Wales; Departments of Veterinary Pathologyt, Veterinary Clinical Studies**, and Medicine$, University of Sydney; $School of Pathology, University of New South Wales; YPacific Highway, Pymble, New South Wales
ABSTRACT Eleven German Shepherd dogs with pituitary dwarfism were examined. They were severely stunted in growth and possessed abnormal hair coats with persistence of the soft puppy (lanugo) coat and symmetrical areas of alopecia. Various other physical defects were often present in affected dogs. Detailed hormonal studies demonstrated a severe deficiency in growth hormone in all five cases so evaluated. A decrease in somatomedin activity was present in three of these cases. Changes in growth plates epiphyses and ossification centres were apparent on radiographic examination of four of the eleven dogs. Epiphyseal dysgenesis was confirmed histologically in two of these cases. Of the six brains which were examined post mortem, four showed large cystic lesions involving the adenohypophysis and two had pituitary hypoplasia with virtual absence of adenohypophyseal tissue. INTRODUCTION Proportionate dwarfism, resulting from pituitary insufficiency has been reported previously. In the majority of cases the breed affected has been the German Shepherd but it has also been observed in the Toy Pinscher, the Spitz and the Carelian Bear dog (Baker, 1955; Jensen, 1959; Alexander, 1962; Muller & Jones, 1973; Andresen, Willeberg & Rasmussen, 1974; Andresen & Willeberg, 1976; Lund-Larsen & Grmdalen, 1976). The purpose of this paper is to record the clinical and some other findings from eleven cases of dwarfism which have been observed in New South Wales, Australia, between December 1975 and December 1976. * Present address: Department of Clinical Sciences, New York State College of Veterinary Medicine, Cornell University, Ithaca, N.Y., U.S.A. 14853. 0020-4510/78/1200-0711$02.0001978 BSAVA
71 1
712
G . S . A L L A N ET A L .
CLINICAL DETAILS Eleven German Shepherd dogs were examined over a 12-month period. In all cases they were presented for examination became of their failure to grow to the anticipated size for the breed, as well as for abnormalities in their hair coat. The principal clinical findings are summarized in Table 1. Their ages at the time of initial examination ranged from 1 to 18 months. In many instances, the owners were aware of their dogs’ decreased growth rate several months prior to presentation. In six cases (Nos 1,4,8-11) the puppies were hand reared from birth, and their breeders were always aware of their comparative failure to grow. In each case the conformation and silhouette was that of a miniature German Shepherd. They were normally proportioned but diminutive in stature (Fig. I). The maximum recorded weight was 13.5 kg and the maximum recorded shoulder height was 47.5 cm. Apart from the variation in size, any difference in their appearance was due to the gross variation in hair cover. In all cases the princi.pa1 hair type was the fine, soft, puppy (lanugo) coat but some dogs had long fluffy coats, whilst the remainder had relatively short coats. In all cases bilaterally symmetrical alopecia was present, involving the perineum, tail, thighs and ventral abdomen. There were isolated patches of primary guard hair development in most cases, but this was restricted to tufts, measuring 1-2 cm diameter, usually scattered haphazardly over the body (Fig. 2). Behavioural disturbances were noted in four of the dogs. This ranged from fear biting, to unprovoked aggression. The aggressive nature of one case was directed indiscriminately to anyone attempting to handle it, and was not overcome by prolonged contact with its owners. In four cases jaw and/or dental abnormalities were recorded, consisting of undershot mandibles (three cases) and failure of the permanent dentition to erupt fully (one case). In the latter case only crowns of the permanent teeth had erupted, with many of the temporary teeth being retained. Except for one unilateral cryptorchid dog the external genitalia of all cases appeared grossly normal, moreover one of the female dogs (No. 4) had been in oestrus. The only other pertinent findings were cardiac machinery murmurs and waterhammer pulses in three of the dogs. In one of these (No. 6) further detailed investigations of the cardiac abnormality confirmed the presence of a patent ductus arteriosus. LABORATORY INVESTIGATIONS Hematology and Biochemistry Blood samples were taken from eight of the cases and submitted to routine hematological and biochemical investigation, using standard techniques. Biochemical evaluation included alkaline phosphatase (SAP), glutamate pyruvate transaminase (SGPT) lactate dehydrogenase (SLDH), total serum protein and
10 11
8 9
1
1
Case No.
6.8
7
'33
6 5 5 5
I I
12
-
26.0 12.0
-
32.4
-
3.4 1.6
6.5 6.7
40.0 47.5 41.5
7.3
18
3.0 9.0 13.0 13.5
33.0
(kg)
I
Shoulder height (cm)
Weight
Age (Months)
normal normal normal normal
fear-biting aggression fear-biting normal normal
female male female male male
Lanugo Lanugo Lanugo Lanugo Lanugo
Lanugo Lanugo Lanugo Lanugo Lanugo
fear-biting and aggression
female
female male female female male
Lanugo
Behaviour
Gender
Principal hair type
TABLE 1. Observations at physical examination of I I Dwarf German Shepherd Dogs
normal seizures Normal P.D.A. undershot mandible
-
incomplete eruption of permanent dentition, P.D.A.. megesophagus normal undershot mandible normal normal undershot mandible unilateral cryptorchid P.D.A.
Other
v1
0
0 0
2P
V
X m
v1
x
v)
9
.-I
z
714
G . S . A L L A N ET A L .
FIG. I . A German Shepherd dwarf (Case No. 10) at 18 months of age. A normal, 15 months old, German Shepherd is included in the photograph for comparison.
FIG 2. German Shepherd dwarf shown in Fig. 1. Note the alopecia around the neck, ventral abdomen and hind-quarters, the fine, soft, lanugo hair coat and the patch of primary guard hair development (arrowed).
715
P I T U I T A R Y DWARFISM I N G E R M A N S H E P H E R D D O G S
protein fractions, determined by cellulose acetate electrophoresis, cholesterol, glucose and the electrolytes, calcium, sodium and potassium. In general the findings were unremarkable. No hematological abnormalities were observed and, apart from two cases (Nos 2 and 4) which showed mild hypercholesterolemia (4 18 and 325 mg/dl respectively), all other examinations performed gave results within the normal range. Hormonal Investigations Hormonal investigations were carried out on the cases indicated in Table 2. Plasma cortisol levels were assayed by a fluorimetric method before, and two hours after, intramuscular administration of 40 units of ACTH gel (ActhaF gel, Armour Pharmaceutical Co.). Plasma thyroxine levels were determined by a competitive protein binding technique before, and 12 hours after, intramuscular administration of 5 units of Thyroid Stimulating Hormone (Thytropar, Armour Pharmaceutical Co.). Somatomedin was measured by a modification of the radioreceptor assay of Marshal et al. (1 974) using human somatomedin prepared and characterised as previously described (Brown et al., 1977; Baxter & Turtle, 1978). Specific binding, i.e. binding displaced by 50 milliunits of somatomedin, was up to 20% (10% in these assays). In two separate assays, serum samples were measured in duplicate at 1 and 2.5 p1 and compared by computer to standard curves covering the range 0-25-10 p1 of a pool of eight normal dog sera. Labelled somatomedin was displaced 50% from receptors by 2 p1 of this pool. The standard pool was arbitrarily assigned a receptor reactive somatomedin concentration of 1 Unit/ml. Dog growth hormone (GH) was measured using the method and TABLE 2. Plasma cortisol, thyroxine, somatomedin and growth hormone activity in Dwarf German Shepherd Dogs Cortisol (ug/dl) Case No. 2 3 6 8
Thyroxine (ug/dl)
Resting
Post ACTH
Resting
Post TSH
Somatomedin (units/ml)
74
9.0 9.5
-
-
-
-
6.5
0.6 I .2
3.4
I .36
7.9
I .09
I .2
Pituitary dwarfism in German Shepherd Dogs G. S . ALLAN*, C. R. R. H U X T A B L E t , C. R . HOWLETTS, R. C. BAXTERS, B. D U F F 7 A N D B. R. H . FARROW** *Kuringai Animal Hospital, New South Wales; Departments of Veterinary Pathologyt, Veterinary Clinical Studies**, and Medicine$, University of Sydney; $School of Pathology, University of New South Wales; YPacific Highway, Pymble, New South Wales
ABSTRACT Eleven German Shepherd dogs with pituitary dwarfism were examined. They were severely stunted in growth and possessed abnormal hair coats with persistence of the soft puppy (lanugo) coat and symmetrical areas of alopecia. Various other physical defects were often present in affected dogs. Detailed hormonal studies demonstrated a severe deficiency in growth hormone in all five cases so evaluated. A decrease in somatomedin activity was present in three of these cases. Changes in growth plates epiphyses and ossification centres were apparent on radiographic examination of four of the eleven dogs. Epiphyseal dysgenesis was confirmed histologically in two of these cases. Of the six brains which were examined post mortem, four showed large cystic lesions involving the adenohypophysis and two had pituitary hypoplasia with virtual absence of adenohypophyseal tissue. INTRODUCTION Proportionate dwarfism, resulting from pituitary insufficiency has been reported previously. In the majority of cases the breed affected has been the German Shepherd but it has also been observed in the Toy Pinscher, the Spitz and the Carelian Bear dog (Baker, 1955; Jensen, 1959; Alexander, 1962; Muller & Jones, 1973; Andresen, Willeberg & Rasmussen, 1974; Andresen & Willeberg, 1976; Lund-Larsen & Grmdalen, 1976). The purpose of this paper is to record the clinical and some other findings from eleven cases of dwarfism which have been observed in New South Wales, Australia, between December 1975 and December 1976. * Present address: Department of Clinical Sciences, New York State College of Veterinary Medicine, Cornell University, Ithaca, N.Y., U.S.A. 14853. 0020-4510/78/1200-0711$02.0001978 BSAVA
71 1
712
G . S . A L L A N ET A L .
CLINICAL DETAILS Eleven German Shepherd dogs were examined over a 12-month period. In all cases they were presented for examination became of their failure to grow to the anticipated size for the breed, as well as for abnormalities in their hair coat. The principal clinical findings are summarized in Table 1. Their ages at the time of initial examination ranged from 1 to 18 months. In many instances, the owners were aware of their dogs’ decreased growth rate several months prior to presentation. In six cases (Nos 1,4,8-11) the puppies were hand reared from birth, and their breeders were always aware of their comparative failure to grow. In each case the conformation and silhouette was that of a miniature German Shepherd. They were normally proportioned but diminutive in stature (Fig. I). The maximum recorded weight was 13.5 kg and the maximum recorded shoulder height was 47.5 cm. Apart from the variation in size, any difference in their appearance was due to the gross variation in hair cover. In all cases the princi.pa1 hair type was the fine, soft, puppy (lanugo) coat but some dogs had long fluffy coats, whilst the remainder had relatively short coats. In all cases bilaterally symmetrical alopecia was present, involving the perineum, tail, thighs and ventral abdomen. There were isolated patches of primary guard hair development in most cases, but this was restricted to tufts, measuring 1-2 cm diameter, usually scattered haphazardly over the body (Fig. 2). Behavioural disturbances were noted in four of the dogs. This ranged from fear biting, to unprovoked aggression. The aggressive nature of one case was directed indiscriminately to anyone attempting to handle it, and was not overcome by prolonged contact with its owners. In four cases jaw and/or dental abnormalities were recorded, consisting of undershot mandibles (three cases) and failure of the permanent dentition to erupt fully (one case). In the latter case only crowns of the permanent teeth had erupted, with many of the temporary teeth being retained. Except for one unilateral cryptorchid dog the external genitalia of all cases appeared grossly normal, moreover one of the female dogs (No. 4) had been in oestrus. The only other pertinent findings were cardiac machinery murmurs and waterhammer pulses in three of the dogs. In one of these (No. 6) further detailed investigations of the cardiac abnormality confirmed the presence of a patent ductus arteriosus. LABORATORY INVESTIGATIONS Hematology and Biochemistry Blood samples were taken from eight of the cases and submitted to routine hematological and biochemical investigation, using standard techniques. Biochemical evaluation included alkaline phosphatase (SAP), glutamate pyruvate transaminase (SGPT) lactate dehydrogenase (SLDH), total serum protein and
10 11
8 9
1
1
Case No.
6.8
7
'33
6 5 5 5
I I
12
-
26.0 12.0
-
32.4
-
3.4 1.6
6.5 6.7
40.0 47.5 41.5
7.3
18
3.0 9.0 13.0 13.5
33.0
(kg)
I
Shoulder height (cm)
Weight
Age (Months)
normal normal normal normal
fear-biting aggression fear-biting normal normal
female male female male male
Lanugo Lanugo Lanugo Lanugo Lanugo
Lanugo Lanugo Lanugo Lanugo Lanugo
fear-biting and aggression
female
female male female female male
Lanugo
Behaviour
Gender
Principal hair type
TABLE 1. Observations at physical examination of I I Dwarf German Shepherd Dogs
normal seizures Normal P.D.A. undershot mandible
-
incomplete eruption of permanent dentition, P.D.A.. megesophagus normal undershot mandible normal normal undershot mandible unilateral cryptorchid P.D.A.
Other
v1
0
0 0
2P
V
X m
v1
x
v)
9
.-I
z
714
G . S . A L L A N ET A L .
FIG. I . A German Shepherd dwarf (Case No. 10) at 18 months of age. A normal, 15 months old, German Shepherd is included in the photograph for comparison.
FIG 2. German Shepherd dwarf shown in Fig. 1. Note the alopecia around the neck, ventral abdomen and hind-quarters, the fine, soft, lanugo hair coat and the patch of primary guard hair development (arrowed).
715
P I T U I T A R Y DWARFISM I N G E R M A N S H E P H E R D D O G S
protein fractions, determined by cellulose acetate electrophoresis, cholesterol, glucose and the electrolytes, calcium, sodium and potassium. In general the findings were unremarkable. No hematological abnormalities were observed and, apart from two cases (Nos 2 and 4) which showed mild hypercholesterolemia (4 18 and 325 mg/dl respectively), all other examinations performed gave results within the normal range. Hormonal Investigations Hormonal investigations were carried out on the cases indicated in Table 2. Plasma cortisol levels were assayed by a fluorimetric method before, and two hours after, intramuscular administration of 40 units of ACTH gel (ActhaF gel, Armour Pharmaceutical Co.). Plasma thyroxine levels were determined by a competitive protein binding technique before, and 12 hours after, intramuscular administration of 5 units of Thyroid Stimulating Hormone (Thytropar, Armour Pharmaceutical Co.). Somatomedin was measured by a modification of the radioreceptor assay of Marshal et al. (1 974) using human somatomedin prepared and characterised as previously described (Brown et al., 1977; Baxter & Turtle, 1978). Specific binding, i.e. binding displaced by 50 milliunits of somatomedin, was up to 20% (10% in these assays). In two separate assays, serum samples were measured in duplicate at 1 and 2.5 p1 and compared by computer to standard curves covering the range 0-25-10 p1 of a pool of eight normal dog sera. Labelled somatomedin was displaced 50% from receptors by 2 p1 of this pool. The standard pool was arbitrarily assigned a receptor reactive somatomedin concentration of 1 Unit/ml. Dog growth hormone (GH) was measured using the method and TABLE 2. Plasma cortisol, thyroxine, somatomedin and growth hormone activity in Dwarf German Shepherd Dogs Cortisol (ug/dl) Case No. 2 3 6 8
Thyroxine (ug/dl)
Resting
Post ACTH
Resting
Post TSH
Somatomedin (units/ml)
74
9.0 9.5
-
-
-
-
6.5
0.6 I .2
3.4
I .36
7.9
I .09
I .2
