Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, USA
Abstract
Endocrinology is the science that studies the influence of hormones on the body. The endocrine system has a major role on normal function of the body. Many diseases can affect the endocrine system, from neoplastic processes to abnormal response to physiological stimuli. Although endocrine disorders are well described in humans and small animals, there is limited information on exotic mammals. This master class will focus on disease processes affecting the endocrine glands and/or systems that are relevant in exotic mammals. During this master class, we will further review endocrine physiology, diagnostic tests for the assessment of the endocrine tissue, and treatment options for specific conditions.
Introduction
Endocrinology is the science that studies the influence of hormones on the body function.1 Endocrine glands are specialized tissues/cells that synthesize, store, and release their hormonal secretions directly into blood.2 The primary function of the endocrine system is to maintain normal metabolic function through internal and external environmental variation; a balance achieved through secretion of different hormones, some antagonistic, others synergistic.3 Endocrine disorders appear to be involved in ∼10 to 20% of canine and approximately 5% of feline disease processes.4 In exotic animals there is relatively little information, but it is a growing field.
Diseases of the Pituitary Gland
Diabetes Insipidus (DI)
DI occurs due to failure to produce or secrete, or lack of renal effects of antidiuretic hormone. DI is further categorized as primary (neurogenic or central), nephrogenic, dipsogenic, or gestational.
Spontaneous DI in exotic small mammal species commonly kept as pets (rats and rabbits) can occur.5-7 Diagnostic tests similar to those described for small animals are also adequate for exotic mammals. The use of the water deprivation test for diagnosing psychogenic polydipsia was reported in a laboratory New Zealand white rabbit (Oryctolagus cuniculus).8 It is important to note that gerbils (Meriones unguiculatus) may become polydipsic (without DI) if food is restricted.9
Neoplasia
Pituitary neoplasms have been reported in multiple species of small exotic mammals (e.g., rabbits, ferrets), but the most prevalent species is rats.10-12 Older female rats are most commonly diagnosed with pituitary neoplasms, and as a consequence, it has been suggested that estrogen may play a role in the disease.13
Reports of pituitary adenomas in pet rats and treatment of clinical cases are rare. A 2-year-old intact male albino pet rat was presented with a 3-week history of hypodipsia, suspected blindness, and behavioral changes.14 The rat was subsequently treated with cabergoline (0.6 mg/kg PO q 72 h).14 Clinical signs recurred at 8.5 months, and a pituitary adenoma was diagnosed on necropsy.14
Diseases of the Thyroid Gland
Clinical Assessment
The most common initial assessment of thyroid function is circulating serum thyroid hormones. Total thyroxine (TT4) test has been shown to have poor sensitivity and specificity for thyroid disease.15 In human medicine, TT4 is not commonly used because the measurement of TT4 and total triiodothyronine (TT3) is unreliable since other nonthyroidal diseases can influence these values. This condition is commonly called euthyroid sick syndrome or nonthyroidal illness syndrome.16 Euthyroid sick syndrome refers to changes in serum TSH, serum thyroid hormones, and tissue thyroid hormone levels that occur in patients with various nonthyroidal conditions; however, it is not a primary thyroid disease.17 In cases of mild illness, only TT3 decreases; however, in severe cases, both TT3 and TT4 decrease.18
Because of the unreliability of the total thyroid hormone measurement, this method has been largely abandoned in human medicine. Measurement of the free hormones, when measured by reliable methods, is more adequate. Furthermore, in cases of euthyroid sick syndrome or nonthyroidal illness syndrome, decreases in free thyroxine (fT4) and free triiodothyronine (fT3) are usually modest when compared to decreases in TT3 and TT4.19 Nonetheless, free thyroid values can also be influenced by other nonthyroidal factors.20
Serum TSH measurement in humans is the single most reliable test to diagnose all common forms of hypothyroidism and hyperthyroidism.21 Unfortunately, this diagnostic test is not validated for non-traditional species.
Another thyroid function diagnostic test, mainly for hypothyroidism, is dynamic testing. Dynamic testing implies administering a certain hormone and determining the physiologic response. Among exotic species, limited studies assessing dynamic thyroidal testing have been published. TRH and TSH stimulation testing have been reported in multiple mammalian species (e.g., rats, mice, ferrets, guinea pigs).22-24
Diagnostic imaging (e.g., nuclear medicine) has long been used for the diagnosis of thyroid dysfunction, specifically cases of hyperthyroidism. Taking advantage of the physiologic iodine/iodide cycle, an isotope with high affinity to the thyroid gland is administered, and uptake by the thyroid gland is either quantified or compared with another organ. Normal ratios have been formulated for small animals and, when elevated, may be indicative of a hyperfunctioning thyroid gland, supporting a possible hyperthyroid diagnosis. Reference intervals of thyroid scintigraphy for exotic species have not been well established, although rabbits have been reported in a non-peer review format.25-27 Other imaging modalities used for thyroid diagnostic testing (e.g., ultrasonography, CT, and MRI) are mainly used for the diagnosis of neoplasia. Furthermore, these tests generally do not provide information regarding functionality.
Thyroid Dysfunction
Guinea Pigs
Guinea pigs (Cavia porcellus) are commonly diagnosed with hyperthyroidism. In addition to clinical reports, thyroid neoplasias have been reported as some of the most common neoplasias (3.6%) detected in guinea pigs by one laboratory service.28 Age and gender predisposition have not been determined, but it appears that there may be a female bias and a higher predisposition for animals older than 3 years.29 Several publications have reported normal thyroid reference intervals for guinea pigs, with specific intervals per sex, age, and environment.30-34 Conversely, hypothyroidism is rarely diagnosed in small mammal species. There is only one limited report of hypothyroidism in a guinea pig, and the case description is nonspecific.29
Rabbits
Although rabbits are one of the most commonly kept exotic small mammal pets and have long been used in medical research, naturally occurring and induced thyroid dysfunction are rarely reported.35-38 Although rabbit clinical thyroid disorders have not been published, the author is aware of several highly suspected cases of thyroid dysfunction. Thyroid dysfunction (e.g., euthyroid sick syndrome or nonthyroidal illness) was induced in rabbits that suffered skin wounds through experimental thermal means and has been reported in clinical cases.37,39-41
Chinchillas
One case of concurrent diabetes mellitus and hyperthyroidism has been reported in a chinchilla (Chinchilla lanigera).42 Although correlation between the two conditions is considered unlikely, hyperthyroidism in cats can impair glucose tolerance, potentially leading to peripheral insulin resistance.42,43
Ferrets
Ferret hypothyroidism has been diagnosed in seven cases based on low basal TT4 values and a limited response after TSH stimulation test.44 The use of recombinant hTSH for stimulation testing has been validated in the ferret. Hypothyroid ferrets had similar clinical signs to other endocrinopathies: obesity, lethargy, inactivity, and excessive sleeping behavior.44 There are at least two reports of thyroid neoplasias identified in ferrets: a C-cell carcinoma (medullary thyroid carcinoma) associated with multiple endocrine neoplasms and a thyroid follicular adenocarcinoma.45,46
Rats
Thyroid neoplasia, euthyroid sick syndrome or nonthyroidal illness, hypothyroidism, and hyperthyroidism have been reported in rats.47,48
Diseases Affecting the Endocrine Pancreas
Neoplasia
Insulinoma is an endocrinologically active insulin-secreting tumor of the pancreatic β cells. Hyperinsulinemia causes hypoglycemia by increased uptake of glucose by muscle tissue, fat, and the liver (all insulin target cells) and suppression of hepatic glycogenolysis and gluconeogenesis.49 Neoplastic hyperfunctioning islet cells continue to produce insulin due to lack of negative feedback.49
Ferrets
Insulinomas are considered the most common reported neoplasias of ferrets, with an incidence of ~25% of all neoplasms diagnosed.50 Insulinomas in ferrets tend to be benign and nonmetastatic, although local metastases have been suggested.50
Rats
Both spontaneous and induced insulinomas have been reported in laboratory rats.51,52 In late stages of the disease, rats exhibited clinical signs of hypoglycemia, tachypnea, and partial limb paralysis.53 The prevalence of spontaneous islet cell adenoma in aged laboratory rats appears to be low, with pancreatic islet cell adenomas reported to represent 2 to 6% of all tumors.54-56
Guinea Pigs
There have been three case reports of insulinomas in guinea pigs.57 Insulinomas do not appear to be a common clinical problem in guinea pigs, with only one case being diagnosed in vivo.
Rabbits
Insulinoma was diagnosed in one rabbit; a serendipitous diagnosis was obtained during a study assessing the usefulness of blood glucose measurement in pet rabbits.58
Diabetes Mellitus (DM)
Rodents
Some rodents, in particular members of suborder Hystricomorpha, have some unique insulin characteristics and therefore unique physiology associated with DM. Spontaneous DM in guinea pigs has been reported in a laboratory colony and in a pet guinea pig.59,60 Degus may be one of the most common exotic small mammal species that develop spontaneous diabetes during obesity.61 In a retrospective study of degu diseases, DM was reported in 12/300, with a majority of animals (10/12) being 2 years old or older.62
Rabbits
Rabbits are used for diabetes research, and cases of spontaneous DM in New Zealand white rabbits have been reported.63 However, spontaneous DM appears to be rare in rabbits.
Ferrets
DM has been reported in ferrets, most commonly iatrogenic following surgical removal of an insulinoma.64 This condition tends to be transient, with insulin and glucose levels normalizing over a period of time. However, normalization of insulin levels may be due to recurrence of the insulinoma. Ferrets with DM may nonetheless require insulin therapy depending on severity of illness and the length of time necessary for resolution. Spontaneous DM unrelated to pancreatectomy and/or spontaneous pancreatitis has been reported.65
Diseases of the Adrenal Gland
Hyperadrenocorticism
Ferrets
Ferret hyperadrenocorticism, commonly called adrenal gland disease, is arguably the most well-studied endocrinopathy of exotic small mammals. Ferret adrenal gland disease is a form of hyperadrenocorticism caused by adrenal tissue hypertrophy and/or neoplasm within the adrenal cortex that overproduces one or more steroid hormones (e.g., glucocorticoids, mineralocorticoids, androgens).50 It is important to mention that this condition is not the same as Cushing’s syndrome (or disease), which is characterized by elevated cortisol levels that result from an ACTH-secreting pituitary tumor or a cortisol-secreting adrenal tumor.50 It has been shown that neutering is the predisposing factor related to the development of hyperadrenocorticism in ferrets, independent of the age at which it is performed.66 Furthermore, pituitary gonadotropic hormones also appear to have an influence on the pathogenesis of hyperadrenocorticism in ferrets.67
Hyperestrogenism
Rabbits
Hypertestosteronism associated with adrenal neoplasia and hyperplasia, leading to increased sexual and aggressive behavior, has been reported in older neutered rabbits.68 Normal rabbit adrenal glands secrete appreciable amounts of sex steroids.68
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