Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Diabetes secondary to endocrine disorders and PCOS.

A number of hormones participate physiologically in the regulation of blood glucose levels, and alterations in their production may cause hyperglycemia. In particular, hormones involved in the counterregulatory response to insulin, such as glucagon, catecholamines, cortisol, or GH, have a potent hyperglycemic action. Although abnormal overproduction of these hormones is rare, these forms of secondary diabetes should be recognized because they merit specific treatments and can even be cured by appropriate management. Exogenous glicorticoid excess is a more common cause of iatrogenic secondary diabetes, which may especially occur in subjects who have risk factors for type 2 diabetes. Somatostatin-secreting tumors, which are very rare, may also cause hyperglycemia, due to inhibition of insulin secretion. Similarly, treatment of some endocrine disorders by somatostatin analogs, particularly pasireotide, may induce hyperglycemia and secondary diabetes. Moreover, several other hormones modulate metabolic processes, with potential alterations of glucose levels in the case of abnormalities in their production. In particular, thyroid hormones regulate several steps of the glucose metabolism, with increased supply of glucose to tissues. In physiological conditions, these effects allow the body to meet the increased energy demand induced by thyroid hormones. However, thyroid dysfunction, especially hyperthyroidism, is associated with frequent alteration of glucose tolerance, with complex interactions with insulin action. There is evidence that sex hormones, by mechanisms that are still not completely understood, may also affect metabolic processes, including impaired insulin sensitivity. In particular, abnormalities in serum androgens are frequently associated with altered glucose levels. In this regard, there is a striking sexual dimorphism, as glucose intolerance is associated with reduced serum testosterone in men, but with increased serum testosterone in women. This latter phenomenon may be especially found in women with the polycystic ovary syndrome (PCOS), who are often insulin resistant. However, PCOS is a heterogeneous condition. Distinguishing the different clinical phenotypes of this syndrome is helpful in estimating the individual risk of metabolic abnormalities of these subjects