CHAPTER 45 The Endocrine System
Endocrine and metabolic disorders affecting puppies and kittens from birth until 6 months of age may manifest as clinical problems related to growth or water metabolism (polydipsia and polyuria). Most commonly, endocrine and metabolic disorders affect growth of the animal; in particular, puppies are often presented to the veterinarian for assessment of delayed or aberrant growth. Other endocrine disorders of small animals, such as juvenile-onset diabetes insipidus (DI) or diabetes mellitus, affect water metabolism resulting in excessive thirst and/or urination, which can cause difficulty during house-breaking.
DI is a disorder of water metabolism characterized by polyuria, urine of low specific gravity or osmolality, and polydipsia. It is caused by defective secretion of antidiuretic hormone (ADH; central DI) or by the inability of the renal tubule to respond to ADH (nephrogenic DI). Deficiency of ADH (or vasopressin) can be partial or complete. Central DI is characterized by an absolute or relative lack of circulating ADH and is classified as primary (idiopathic and congenital) or secondary. Secondary central DI usually results from head trauma or neoplasia. Both central DI and nephrogenic DI are rare disorders.
Central DI may appear at any age, in any breed, and in either gender; however, young adults (6 months of age) are most commonly affected. The major clinical signs of DI are profound polyuria and polydipsia (>100 ml/kg/day; normal, 40 to 70 ml/kg/day), nocturia, and incontinence usually of several months’ duration. The severity of the clinical signs varies because DI may result from a partial or complete defect in ADH secretion or action. Other less consistent signs include weight loss because these animals are constantly seeking water, as well as dehydration.
Routine complete blood count, serum biochemical, and electrolyte profiles are usually normal in animals with DI. Plasma osmolality will often be high (>310 mOsm/L) in those with central or nephrogenic DI as a result of dehydration. Puppies with primary (psychogenic?) polydipsia will often exhibit low plasma osmolality (<290 mOsm/L) as a result of overhydration. When abnormalities such as a slightly increased hematocrit or hypernatremia are present on initial evaluation, they are usually secondary to dehydration from water restriction by the pet owner. In DI, the urinalysis is unremarkable except for the finding of persistently dilute urine (urine specific gravity, 1.004 to 1.012).
Diagnostic tests to confirm and differentiate central DI, nephrogenic DI, and psychogenic polydipsia include the modified water deprivation test or response to ADH supplementation. The modified water deprivation test is designed to determine whether endogenous ADH is released in response to dehydration and whether the kidneys can respond to ADH. The more common causes of polyuria and polydipsia should be ruled out before this procedure. Failure to recognize renal failure before water deprivation may lead to an incorrect or inconclusive diagnosis or cause significant patient morbidity. Normal renal concentrating abilities are not present in a puppy until 4 to 6 months of age. Congenital renal dysplasia can cause early signs of renal failure. A simpler way to differentiate between primary or psychogenic polydipsia and DI is to compare water consumption before and 3 to 5 days after desmopressin acetate administration (2 to 3 drops nasally twice daily); a 50% reduction in water consumption is consistent with a diagnosis of central DI.
Treatment consists of replacement of the deficient hormone (ADH) in the form of desmopressin acetate. Desmopressin, used to treat bedwetting in children, is available as a nasal spray; however, the nasal delivery apparatus should be removed before administration to a dog or cat as it can be uncomfortable for them. Two to 3 drops of desmopressin acetate nasally or onto the conjunctival sac twice daily is recommended to control polydipsia and polyuria in most animals with DI. It is important to counsel clients about the fact that water deprivation in the untreated central DI patient can be problematic.
Many pediatric endocrine disorders are manifested as abnormalities of statural growth. Causes of inadequate growth can be divided into two broad categories: intrinsic defects of growing tissues (skeletal dysplasias, chromosomal abnormalities, and dysmorphic dwarfism) and abnormalities in the environment of growing tissues (nutritional, metabolic, environmental, and endocrine). Intrinsic defects of growing tissues include most of the genetic and chromosomal abnormalities that result in growth failure. Genetic disorders may be suspected based on clustering of disease in certain breeds or lines of dogs and cats (e.g., chondrodystrophy of Alaskan Malamutes). Diagnosis may require pursuing pedigree analysis, genetic testing, or both.
Abnormalities of the environment of growing tissues are the most common and easily identified disorders. A thorough dietary history will reveal inadequate quantity and/or quality of feeding. Metabolic disorders, such as portosystemic shunting, pancreatic insufficiency, congenital heart disease, and congenital renal failure, may be identified by characteristic clinical signs and laboratory data. Endocrine causes of growth retardation include juvenile hypothyroidism, juvenile type I diabetes mellitus, juvenile hyperadrenocorticism, and hypopituitarism.
Endocrine growth abnormalities can be divided into two groups based on the type of dwarfism present. A proportionate dwarf exhibits small stature but precisely the same dimensions as the adult animal; proportionate dwarfism is characteristic of isolated growth hormone (GH) deficiency. In contrast, a disproportionate dwarf has a normal-sized head and trunk with short legs; disproportionate dwarfism is characteristic of hypothyroid- and hyperadrenocorticism-mediated dwarfism (Figure 45-1). Other endocrine causes of abnormal growth (e.g., juvenile diabetes mellitus) result in subnormal stature (not true dwarfism) and a normally proportioned, emaciated animal.
Pituitary dwarfism results from destruction of the pituitary gland via a neoplastic, degenerative, or anomalous process. It may be associated with decreased production of other pituitary hormones, including thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and GH. Pituitary dwarfism is most common in German Shepherd Dogs 2 to 6 months of age. Other affected breeds include Carnelian Bear Dogs, Spitz, Miniature Pinschers, and Weimaraners. The disease is inherited as a simple autosomal recessive trait in German Shepherd Dogs and occurs as a result of cystic Rathke’s pouch. The first observable clinical signs of pituitary dwarfism are slow growth noticed in the first 2 to 3 months of life and mental retardation usually manifested as difficulty in house-training. Physical examination findings may include proportionate dwarfism, retained puppy haircoat, hypotonic skin, truncal alopecia, cutaneous hyperpigmentation, infantile genitalia, and delayed dental eruption. Clinicopathologic features include eosinophilia, lymphocytosis, mild normocytic normochromic anemia, hypophosphatemia, and occasionally hypoglycemia resulting from secondary adrenal insufficiency. Differential diagnoses include other causes of stunted growth, such as hypothyroid dwarfism, portosystemic shunt, diabetes mellitus, hyperadrenocorticism, malnutrition, and parasitism. Diagnosis is made by measuring serum GH concentrations (no longer commercially available) or serum somatomedin C (insulin-like growth factor 1 [IGF-1]). The advantage of IGF-1 is that it is not species specific. There is usually a subnormal response to exogenous TSH and ACTH stimulation tests; furthermore, endogenous TSH and ACTH are decreased in affected dogs as a result of panhypopituitarism. A thyrotropin-releasing hormone (TRH) stimulation test would be abnormal as well.