Panhypopituitarism in young dogs usually results from failure of the pars distalis of the pituitary to develop during gestation, which in turn leads to a deficiency of all the pituitary tropic hormones. Some cases are due to benign craniopharyngiomas, which lead to subnormal amounts of growth hormone. Dwarfism results from a lack of growth hormone, with pars distalis failure leading to a range of other clinical signs associated with the lack of other hormones. Hormone assays and genetic testing can be useful for diagnosis. Treatment with thyroid hormone or progestagens can have marked adverse effects. Affected dogs have shortened lifespans.
"Panhypopituitarism" refers to decreased secretion of all pituitary hormones. Juvenile-onset panhypopituitarism, also known as pituitary dwarfism or congenital hyposomatotropism, is an important cause of failure to grow in dogs.
Etiology of Juvenile-Onset Panhypopituitarism in Dogs
Pituitary dwarfism is associated primarily with a failure of the oropharyngeal ectoderm of the cranial pharyngeal duct (the Rathke pouch) to differentiate into tropic hormone–secreting cells of the pars distalis. Consequently, the adenohypophysis does not completely develop.
A mutation in the LHX3 gene, which encodes for a transcription factor necessary for pituitary development, is responsible. It is inherited as a simple autosomal recessive trait.
The second most common cause of pituitary dwarfism is craniopharyngioma, a benign tumor derived from the oropharyngeal ectoderm of the Rathke pouch. Compared with other types of pituitary neoplasms, craniopharyngiomas tend to develop in younger dogs. Craniopharyngiomas cause subnormal secretion of growth hormone (GH), which results in dwarfism.
Epidemiology of Juvenile-Onset Panhypopituitarism in Dogs
Juvenile-onset panhypopituitarism occurs most frequently in German Shepherd Dogs. However, it has been reported in other breeds, such as the Spitz-type dogs, the Miniature Pinscher, and the Karelian Bear Dog.
Clinical Findings of Juvenile-Onset Panhypopituitarism in Dogs
Dwarf pups are indistinguishable from unaffected littermates up to 2 months old. After that, the slower growth rate compared with littermates, retention of puppy coat, and lack of primary guard hairs gradually become evident. German Shepherd Dogs with pituitary dwarfism appear coyote- or foxlike, owing to their small size and soft, woolly coat (see pituitary dwarfism image).
Courtesy of Dr. Deborah Greco.
Clinical signs of pituitary dwarfism include the following:
Bilaterally symmetrical alopecia develops gradually and often becomes complete except for the head and tufts of hair on the legs.
Permanent dentition is delayed or completely absent.
Closure of the epiphyses is delayed up to 4 years, depending on the severity of the hormonal insufficiency; this delay is due to deficiencies of both thyroid-stimulating hormone (TSH) and GH.
The testes and penis are small, calcification of the os penis is delayed or incomplete, and the penile sheath is flaccid.
The ovarian cortex is hypoplastic, and estrus is irregular or absent.
Lifespan is shortened because of resulting secondary endocrine dysfunction, including hypothyroidism and hypoadrenocorticism.
Puppies with panhypopituitarism often have a shrill bark.
Lesions
In cases of juvenile-onset panhypopituitarism due to failure of oropharyngeal ectoderm of Rathke’s pouch to differentiate, Rathke’s pouch is typically cystic. Pituitary cysts fill with mucus and eventually occupy the entire pituitary, severely compressing the pars nervosa and infundibular stalk.
Craniopharyngiomas are large, solid, cystic masses that extend into the overlying hypothalamus. They can also grow along the ventral aspect of the brain, where the incorporation of several cranial nerves results in specific nerve function deficits.
Diagnosis of Juvenile-Onset Panhypopituitarism in Dogs
Hormone assays
Challenge with exogenous thyrotropin or adrenocorticotropin
IGF-1 assay
Genetic testing
In juvenile-onset panhypopituitarism in dogs, concentrations of thyroxine, triiodothyronine, and cortisol are decreased or are in the low-normal range. In animals with an equivocal change in basal hormone concentration, the responses to challenge by exogenous thyrotropin or adrenocorticotropin are subnormal owing to hypoplasia or atrophy of the thyroid gland and adrenal cortex.
Other useful diagnostic aids include comparison of height with that of littermates, skeletal radiography showing delayed epiphyseal closure or dysgenesis, and skin biopsy.
Cutaneous lesions include hyperkeratosis, follicular keratosis, hyperpigmentation, adnexal atrophy, loss of elastin fibers, and a loose network of collagen fibers in the dermis. Hair shafts are absent, and hair follicles are primarily in the telogen stage of the growth cycle.
The activity of insulin-like growth factor 1 (IGF-1; formerly called somatomedin C) is low in dwarf dogs. Intermediate IGF-1 activity is present in phenotypically normal ancestors suspected to be heterozygous carriers.
Assays for IGF-1 provide an indirect measurement of circulating GH activity in dogs with suspected pituitary dwarfism. Basal concentrations of circulating canine GH are reported to be detectable but low (normal range 1.75 ± 0.17 mg/mL) in pituitary dwarfs, and they do not increase after a provocative test for secretion that follows clonidine injection (10 mcg/kg, IV, once), as they do in healthy dogs.
Insulin hypersensitivity has been demonstrated in dogs with pituitary dwarfism, probably because of a change in insulin receptor numbers or in the affinity of binding in response to the low concentration of growth hormone.
Genetic tests for the LHX3 mutation in several breeds are available.
Treatment of Juvenile-Onset Panhypopituitarism in Dogs
Hormone supplementation
Treatment of pituitary dwarfism in dogs is limited to levothyroxine supplementation for secondary hypothyroidism (22 mcg/kg, PO, every 12 hours) and supplementation with porcine somatotropin (0.1–0.3 U/kg, SC, 3 times/week for 4–6 weeks) or medroxyprogesterone acetate (2.5–5.0 mg/kg, IM or SC, every 3 weeks until clinical response [usually 2–4 months], then every 6 weeks) to promote GH secretion from mammary tissue.
With medroxyprogesterone acetate treatment, adverse effects such as acromegalic features, pyometra, insulin resistance, and mammary hyperplasia have been observed.
Key Points
Pituitary dwarfism is a rare, inherited disorder of growth hormone deficiency in the dogs.
The most common clinical signs are proportional dwarfism and secondary hypothyroidism (alopecia).
Treatment with progestagens can reverse some of the clinical signs of dwarfism but is associated with some adverse effects.
For More Information
Paw Print Genetics: Pituitary Dwarfism (Shepherd Type)
Also see pet owner content regarding juvenile-onset panhypopituitarism in dogs.
