Many faces of endocrine diseases

Diabetes mellitus (DM) is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances in the metabolism of carbohydrates, fats and proteins, resulting from defects in insulin secretion or insulin sensitivity in target tissues, or both. Within the ‘specific types of DM’, a subtype of DM related to endocrinopathies is described (acromegaly, Cushing syndrome, pheochromocytoma, primary hyperaldosteronism, hyperthyroidism, glucagonoma and other neuroendocrine tumors).

DM in dogs and cats can be classified as insulin-deficient DM (beta [β] cell-related disorders) and insulin-resistant DM (target-organ disorders).

In domestic cats, it has been estimated that around 80% of cases present with type 2 DM, which is a heterogeneous disease attributable to a combination of insulin resistance and β cell failure. Within the ‘insulin-resistant DM’ category, the following endocrinopathies have been reported in cats: hypersomatotropism (HST), hyperthyroidism, hypercortisolism (HC) and primary hyperaldosteronism with hyperprogesteronism.

Acromegaly

HST, or acromegaly, is an emerging disease in diabetic cats. Although for many years it was considered a rare disease, studies carried out in Europe have indicated that between 17.8% (the Netherlands and Switzerland) and 24.8% (the UK) of diabetic cats have an excess of growth hormone (GH).

Acromegaly is caused by excess secretion of growth hormone (GH) in adult animals. In cats, it is due to GH-secreting tumors of the anterior pituitary. Signs related to diabetes mellitus are typically the first clinical signs noticed. Growth of the extremities, skull, and muscles occur in some cats. Cardiomegaly and azotemia develop late in the disease.

Organomegaly, including renomegaly, hepatomegaly, and enlargement of endocrine organs, is also seen. Some, but not all, cats show the classic enlargement of extremities, body size, jaw, tongue, and forehead that is characteristic of acromegaly in people. Some of the most striking manifestations are seen in the musculoskeletal system and include an increase in muscle mass and growth of the acral segments of the body, including the paws, chin, and skull. Stridor may be detected as a result of increased soft-tissue enlargement of the epiglottis and surrounding tissues.?

Hyperthyroidism

Hyperthyroidism develops over time, transitioning from normal thyroid tissue to hyperplasia to adenoma (and, rarely, carcinoma). By the time cats are diagnosed with hyperthyroidism, almost all will have adenomatous disease (tumors), not hyperplasia.

Diabetes mellitus (DM) and thyroid dysfunction (TD) often tend to coexist in patients. Both hypothyroidism and hyperthyroidism are more common in type 2 diabetes mellitus.

Autoimmune thyroid dysfunction occurs in 17% to 30% with type 1 diabetes

Thyroid dysfunction is more common in patients with type 2 diabetes

Preexisting diabetes mellitus is exacerbated by hyperthyroidism

Insulin treatment should be adjusted in patients with diabetes after the occurrence of thyroid dysfunction

Hyperglycemia should be reevaluated in hyperthyroid subjects after the control of thyroid dysfunction

Hyperthyroidism and thyrotoxicosis can worsen subclinical diabetes mellitus and cause hyperglycaemia in type 2 diabetes mellitus?patients, increasing the risk of diabetic complications. Type 2 diabetes mellitus reduces thyroid-stimulating hormone levels and impairs the conversion of thyroxine (T4) to triiodothyronine (T3) in the peripheral tissues. Poorly managed diabetes mellitus can lead to insulin resistance and hyperinsulinaemia.?

Controlling hyperthyroidism can reduce GFR by up to 50 percent, which may act to worsen any pre-existing kidney disease or unmask renal disease that was not previously detected.?

Hyperthyroidism in cats is associated with the development of hypertrophic cardiomyopathy but the exact mechanism is unknown. It has been suggested that the left ventricle of the heart becomes enlarged as a secondary response to the direct and indirect effects of elevated amounts of thyroid hormones, which include systemic hypertension, increased heart rate, increased myocardial contractility, sympathetic nervous system activation and an increase in the cellular oxygen demand.

Hyperthyroidism will often result in elevated levels of liver-derived enzymes such as alanine aminotransferase (ALT) and alkaline phosphatase (ALKP). The mechanism for the increase in these liver enzymes is unknown.

Usually the enzymes are only mildly elevated, and it has been suggested that an elevation up to 500U/L for ALT and ALKP can be due to hyperthyroidism, whereas elevation above 500U/L may be suggestive of primary hepatobiliary disease.

Diabetic Retinopathy

In contrast to other animal models of diabetes, the ocular lens of the adult cat is resistant to the development of diabetic cataracts.

The changes included early nonleaking microaneurysms, scattered punctuate intraretinal hemorrhages, capillary nonperfusion, and possibly neovascularization. Thickening of the capillary basement membrane, one of the earliest histological changes in human diabetic retinopathy, occurs in experimental diabetes in cats and is in part inhibited by an aldose reductase inhibitor.

The pathogenesis of diabetic retinopathy is complex, but retinal hypoxia appears to play a significant role. Hypoxia stimulates increased production of vascular endothelial cell growth factor (VEGF?1?), which in turn promotes neovascularization, a major cause of blindness in diabetes.

The inner half of the retina of the cat becomes hypoxic early in diabetes, before capillary closure and nonperfusion become clinically apparent.

Increased VEGF expression and neovascularization can also be stimulated by regional acidosis.

Regional acidosis could be due in part to anerobic glycolysis in a hypoxic environment. The retinal hypoxia noted in diabetic cats may result from capillary plugging or altered flow through microaneurysms. Abnormal blood rheology and leukocyte deformability have been documented in diabetic?cats.

Text credit:https://www.msdvetmanual.com/endocrine-system/the-pituitary-gland/feline-acromegaly

https://academic.oup.com/ilarjournal/article/47/3/234/669562