Diabetes Secondary to Pituitary Diseases

In endocrinology, secondary diabetes is diabetes that results as a consequence of another medication or endocrine disease. Among pituitary diseases, acromegaly and Cushing syndrome are typical endocrine disorders causing impaired glucose tolerance (IGT) or overt secondary diabetes mellitus (DM), through various mechanisms, ranging from increased insulin resistance mainly in early stage, to decreased insulin secretion frequently in advanced stage. Various degrees of alteration in glucose metabolism are also present in patients affected by growth hormone (GH) deficiency and hyperprolactinemia. GH plays physiological effects on glucose metabolism, stimulating gluconeogenesis and lipolysis, which results in increased blood glucose and free fatty acid levels. Conversely, insulin-like growth factor 1 (IGF-I) enhances insulin sensitivity primarily on skeletal muscles, but this latter effect is unable to counteract the degree of insulin resistance determined by GH excess. Therefore, GH-induced insulin resistance is considered to be the major mechanism involved in the disorders of glucose metabolism in patients with acromegaly. In acromegaly the prevalence of glucose disorders ranges from 6 to 56%, mainly correlated to hormone levels, duration of disease, family history of diabetes and age of patients. In addition, the interplay between glucose tolerance and acromegaly could become more complicated when we consider the medical treatment with somatostatin analogues (SA). Indeed, SA should ameliorate abnormalities of glucose metabolism due to reversal of insulin resistance and a reduction in gluconeogenesis secondary to decrease in GH levels, but they may also worsen it because of their inhibitory effect on pancreatic insulin secretion. Untreated GH deficiency is associated with a cluster of cardiovascular risk factors, which may also include various degrees of glucose impairment, and GH treatment seems to impact on many of these alterations leading to important changes in glucose metabolism. GH treatment has therefore been suggested to impair glucose metabolism because of the anti-insulin effect of GH and its direct effect on beta-cell and these effects are balanced by the body composition change during treatment. Hypercortisolism leads to hyperglycaemia and insulin resistance, stimulates glicogenolisis and hepatic gluconeogenesis and plays a direct role on pancreatic insulin secretion. Therefore, in Cushing syndrome the prevalence of disorders in glucose metabolism ranges from 20 to 50%, mainly correlated to hormone levels and duration of disease. Medical treatment with the multireceptor-targeted SA Pasireotide is frequently associated with hyperglycemia-related adverse events (from 68 to 73%), thus potentially worsening an already unstable glucose tolerance. The role of prolactin (PRL) as a metabolic hormone is not fully known. Hyperprolactinaemia can be associated with glucose abnormalities or hyperinsulinaemia, although the mechanisms of these associations are still poorly understood. Consequently, a lower risk of metabolic syndrome have been associated with the normalization of PRL during dopamine agonists (DA) treatment. The mechanisms by which DA could improve glucose metabolism may include suppression of endogenous glucose production or increased splanchnic glucose uptake after glucose ingestion.

This Topic will provide an overview of the current state of the art about the different aspects (epidemiology, pathophysiology, impact of treatment, management) of glucose metabolism disorders in some of the most important pituitary diseases, by summarizing the data available in the literature.