Boyd R. Jones, BVSc, FACVSc, DECVIM, MRCVS
Diabetes mellitus and hyperthyroidism are diagnosed commonly in cats but other endocrinopathies are much less common. The less common endocrinopathies include; hypothyroidism, acromegaly, hypoadrenocorticism, hyperadrenocorticism, hyperaldosteronism, hypo and hyperparathyroidism, diabetes insipidus, phaeochromocytoma and insulinoma. In this presentation I will address a number of these endocrinopathies.
Hypothyroidism is rare as the acquired form in adult cats and as a congenital disease in young animals. The acquired form occurs uncommonly after bilateral thyroidectomy or radioiodine treatment of the hyperthyroid cat. Lymphocytic thyroiditis, the most common cause of hypothyroidism in dogs, has been reported in an adult cat and there is an inherited form of lymphocytic thyroiditis reported in a family of cats1. The clinical signs of acquired hypothyroidism in adults can be difficult to identify, as the only appreciable clinical sign may be lethargy but apathy, hypothermia, seborrhea sicca and a puffy face may be seen.
Congenital hypothyroidism due to inherited defects in thyroid hormone synthesis has been documented in recent years. Thyroid gland agenesis, thyroid peroxidase deficiency and primary hypothyroidism due to thyrotropin resistance have been reported2.
Recent studies have shown that non-thyroidal illness will have an effect on the serum total and free thyroxine concentrations. The circulating thyroid hormone concentration may be significantly decreased. Some diseases are more consistently associated with diminished total thyroid hormone (TT4) concentrations: diabetes mellitus, renal disease, liver disease and systemic neoplasia. The severity of the illness correlated with the degree of TT4 suppression. However free T4 concentrations were within the reference range and sometimes elevated in cats with non-thyroidal illness.
The clinical signs of congenital hypothyroidism are summarised in Table 1. They can be mild or severe depending on the nature of the metabolic defect.
Table 1. Clinical signs expected with congenital hypothyroidism (Cretinism)
Short broad head
Delayed closure of growth plates
Short rounded body
Soft fluffy coat
Retained deciduous teeth
At birth affected kittens can appear normal but by four to six weeks their growth rate slows and early death may occur. They remain immature as shown by disproportionate dwarfism, shorter limbs, large broad heads and short rounded bodies. Lethargy and mental depression can be pronounced. Replacement of temporary teeth is delayed and there may be weight loss and recurrent severe constipation.
There may be goitre depending on the underlying defect and whether the thyroid gland has responded to stimulation from excess thyroid stimulating hormone (TSH) concentrations, e.g., in peroxidase deficiency.
In adult cats with iatrogenic hypothyroidism skin changes (seborrhea sicca, matting) are a predominant feature, along with lethargy, depression, weight gain, hypothermia and bradycardia.
Hair may be epilated easily, and regrowth is prolonged where the coat has been clipped. Alopecia is not a common feature, but some cats do lose hair from the pinnae. Puffy facial features associated with myxoedema, obesity and profound apathy are reported.
Some hypothyroid cats may show hypercholesterolemia and mild anaemia. Confirmation of hypothyroidism can be obtained by measuring the serum thyroxine concentration below the reference range and demonstrating failure to respond to exogenous TSH and/or thyrotropin releasing hormone (TRH). The TT4 concentration for euthyroid four-week-old kittens is 62 ± 10 nmol/L. The total T4 concentration in new-born kittens is approximately half that of their mother. By two weeks of age this value increases twofold.
In adult cats many variables affect the basal TT4 concentration including concurrent non-thyroidal illness. Thyroid function testing, especially the TSH stimulation test or the TRH stimulation test are required to confirm hypothyroidism, or determine reduced thyroid hormone secretion associated with non-thyroidal illness.
Hypothyroid cats should show only a mild increase in T4 values. The responsiveness of TT4 to exogenous TSH can be variable and erratic in healthy cats. A parenteral recombinant human TSH preparation has become available recently and appears to be a useful, albeit expensive, alternative to the bovine preparation. Species specific validated feline TSH assay is not yet available.
Radioiodine uptake studies can be useful. Where the gland is absent, destroyed by a pathological process or if there is a deficiency of TSH there will be failure of 131I or technetium uptake. However, with peroxidase defects the glands should sequester a larger amount of iodide than normal, but the sequestered iodide is not organified and a significant proportion of the iodide is released from the gland when sodium perchlorate is administered (no release in normal cats).
Affected cats and kittens should respond to thyroxine supplementation (10-20 µg/kg daily per os). In the congenital disease there may be some increase in growth closure of epiphyses, shedding of temporary dentition and improvement in mental attitude. This dose should be increased or decreased according to response.
HYPERADRENOCORTICISM (Cushing's Syndrome)
Most of the reported cases of hyperadrenocorticism are middle aged to older female cats. There is a high (>75%) incidence of concurrent diabetes mellitus. Polydipsia, polyuria, polyphagia are common clinical signs. The characteristic clinical signs are: a pot bellied obese cat with hepatomegaly and muscle wasting. Skin signs include increased skin fragility and the skin can tear with normal handling or activity. The coat is often unkempt with areas of alopecia.
Lymphopenia, eosinopenia and mature leucocytosis occur inconsistently. Hyperglycaemia and hypercholesterolemia are the most common laboratory abnormalities. High serum alkaline phosphatase activities is uncommon (20% cats), a contrast to dogs.
Urine specific gravity is seldom very dilute (often >1.020) and urea is often normal despite polyuria. ACTH stimulation testing is not as definitive in cats as the screening test is in dogs, with normal results found in up to 50% of cats with hyperadrenocorticism. The urine cortisol-to-creatinine ratio (UCCR) is a highly sensitive screening test which helps diagnose hyperadrenocorticism in cats; but false-positive test results may be seen in cats with moderate to severe non-adrenal illness that do not have hyperadrenocorticism. The low-dose (0.01 mg/kg) dexamethasone suppression test provides diagnostic results that confirm the diagnosis in almost all cats with hyperadrenocorticism, but the test lacks specificity.
The high dose dexamethasone (0.1mg/kg) identifies approximately 75% of pituitary dependent (PDH) cases and 100% of adrenal tumours and is not influenced by non-adrenal illness. For this reason a higher (1.0mg/kg) suppression test has been recommended for cats. An alternate approach is to measure endogenous ACTH which differentiates PDH (normal to elevated ACTH values) from adrenal tumours (low ACTH values).
Ultrasonographic and radiographic evaluation of the adrenals are useful to help differentiate the cause of hyperadrenocorticism; tumour or hyperplasia.
Treatment of hyperadrenocorticism include administration of adrenocorticolytic agent mitotane (o,p1-DDD), drugs that block cortisol synthesis (e.g., trilostane), unilateral adrenalectomy for adrenocortical tumour, bilateral adrenalectomy or hypophysectomy for pituitary-dependent hyperadrenocorticism, or radiation therapy for pituitary adenoma. Adrenalectomy is the most successful treatment for cats. Medical management and pituitary radiotherapy show variable outcomes.
Adrenalectomy is the most successful method of treating cats with hyperadrenocorticism. Unilateral adrenalectomy should be performed in cats with functional unilateral adrenocortical tumours, whereas bilateral adrenalectomy must be performed in cats with bilateral adrenocortical hyperplasia resulting from PDH. After unilateral adrenalectomy glucocorticoid supplementation is required for approximately 2 months, until the atrophied contralateral gland recovers. By contrast, cats undergoing bilateral adrenalectomy require consistent, lifelong replacement of both mineralocorticoid and glucocorticoid hormones.
Hypoadrenocorticism is uncommon (25-30 reported cases). There is no sex predilection and a wide ranges of ages (1-14 years). All reports were in neutered cats.
Clinical signs include lethargy, anorexia, weight loss and, less commonly, vomiting and polydipsia. Clinical signs often wax and wane or respond to symptomatic treatment (fluids, steroids). The most common findings on physical examination include; depression, weakness, hypothermia, dehydration, slow capillary refill and weak pulse. Bradycardia and collapse are not common signs in the cat.
Most cats with primary hypoadrenocorticism have the classical electrolyte changes; hyponatremia, hypochloremia and hyperkaliemia associated with mineralocorticoid deficiency. The extracellular fluid volume contraction (and subsequent decreased renal perfusion) associated with primary adrenocortical insufficiency in cats results in prerenal azotemia and hyperphosphatasemia. Be careful not to misdiagnose cats with hypoadrenocorticism as having renal failure. Urine specific gravity values are variable but are more dilute than would be expected in a cat with prerenal azotemia. Hematological changes include lymphocytosis and eosinophilia, as well as a normocytic, normochromic, non-regenerative anaemia.
The most accurate screening test for hypoadrenocorticism in cats is the ACTH stimulation test. The finding of a low basal serum cortisol concentration with a subnormal or negligible response to ACTH is indicative of adrenocortical insufficiency.
Long-term management of cats with primary hypoadrenocorticism requires lifetime mineralocorticoid and glucocorticoid supplementation. Oral fludrocortisone acetate (0.1 mg/day) or intramuscular injections of repositol desoxycorticosterone pivalate (DOCP; 12.5 mg/month) have been successful in maintaining cats with hypoadrenocorticism. The dose of mineralocorticoid is adjusted as needed, based on follow-up serum electrolyte concentrations monitored every 1-2 weeks during the initial maintenance period. Glucocorticoid supplementation can be provided as oral prednisolone, at the dosage of 1.25 mg/day, or intramuscular methylprednisolone acetate, at the dosage of 10 mg/month. The long term prognosis for most cats with hypoadrenocorticism good.
This endocrine disease is caused by excessive growth hormone (GH) secretion by an adenoma of the pituitary gland. It occurs in older cats, usually neutered males over 8 years of age and is characterised by the overgrowth of bone, connective tissue and viscera.
Polyphagia, polydipsia and polyuria are related to diabetes mellitus from insulin resistance. Several factors contribute to this insulin resistance including a decrease in insulin receptors, increased insulin binding to the receptors and post-receptor antagonism. Despite concurrent diabetes these cats seldom develop ketoacidosis and gain rather than lose weight. Secondary hypertrophic cardiomyopathy is common (dyspnoea, tachycardia, arrhythmias). Bone and joint changes (arthropathy) and occasional neurological signs (due to tumour expansion) occur.
Acromegaly must be suspected when diabetes mellitus is resistant to insulin treatment. GH measurement or insulin growth factor (somatomedin) measurement may help establish a diagnosis if either are elevated.
Diagnostic investigations may reveal secondary changes associated with the acromegaly. Radiography and ultrasonography may show evidence of cardiomegaly, cardiac hypertrophy and pulmonary oedema. The organomegaly and arthropathy may also be evident on radiographs. Other blood changes which may be seen associated with the anabolic and metabolic effects of acromegaly are mild polycythemia, increased liver enzymes, increased cholesterol, increased protein and increased phosphate, often in the absence of azotemia. If available, CT or MRI scans enable identification of a pituitary tumour but will not differentiate between acidophilic and chromophobe adenomas.
Irradiation has been of some value in treating the pituitary tumour. The efficacy of somatostatin analogues (octreotide) and dopaminergic agents have not been fully investigated in cats, but bromocriptine (commencing at 0.2 mg daily) may have some effect, especially in reducing insulin requirements. The major complication of the disease, diabetes mellitus, must be controlled with high doses of insulin, often 20 to 130 IU/day. The cardiomyopathy may need to be controlled with diltiazem, diuretics and ACE inhibitors. The short-term prognosis is reasonable and cases can be managed successfully for one to two years before signs associated with tumour enlargement occur.
Primary hyperaldosteronism (Conn's Syndrome) is rare (<15 reported cases). The increase in aldosterone production is due to an aldosterone secreting tumour of the adrenal cortex.
The clinical signs of hyperaldosteronism are non-specific and include weakness, lethargy, depression, polydipsia and polyuria, all of which are likely to be due to hypokalemia. The generalised muscular weakness may manifest as weakness, cervical ventroflexion, reluctance to move, poor muscle tone and muscle pain.
Hypokalemia with a serum potassium concentration <3.0 mmol/l is a consistent finding in cases of hyperaldosteronism. Profound hypokalemia together with an inappropriately high plasma aldosterone concentration and normal or low fasting plasma rennin concentration provides a definitive diagnosis of primary hyperaldosteronism. Abdominal ultrasonography can be used to image each adrenal gland for evidence of pathology. Some cats with hyperaldosteronism are hypertensive.
Potassium gluconate is administered orally at a dose of 2-4 mmol/day with dosage adjustment based on the daily serum potassium concentration. The potassium-sparing diuretic, spironolactone, is a powerful receptor antagonist and has been shown to be successful in augmenting potassium supplementation in the treatment of hypokalemia in cases of primary hyperaldosteronism. Surgical adrenalectomy for aldosterone-secreting adrenocortical tumours can be curative. The cat's electrolyte, fluid and metabolic imbalance must be corrected first to minimise perioperative complications. If the adrenal mass cannot be removed or removal is incomplete, then continued medical management using oral potassium supplementation and spironolactone are indicated.
Tumours of the adrenal medulla (phaeochromocytoma) are extremely rare. Of the. few cats with phaeochromocytoma that have been reported, functional (i.e., catecholamine secreting) adrenal phaeochromocytoma has been documented in one cat. The phaeochromocytoma developed in an 11-year-old female cat which had clinical signs of polyuria and polydipsia, as well as hypertension. Abdominal ultrasonography revealed an abdominal mass cranial to the left kidney. After surgical excision of the large adrenal gland, the polyuria, polydipsia and hypertension resolved.
Diagnosis should be confirmed by determination of plasma and urinary catecholamines and their metabolites (e.g., vanillylmandelic acid).
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2. Duesberg C and Petersen ME (1997) Adrenal disorders in cats. Journal of Small Animal Practice 27, 321-347.
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4. Jones, BR and Mooney CT (2004) Unusual Thyroid Disorders. Chapter in Small Animal Endocrinology, 3rd Edition, BSAVA (in Press)