The secondary occurrence of
type 2 diabetes with various hormonal diseases (e.g. pituitary, adrenal and/or
thyroid diseases) is a recurrent observation. Indeed,
impaired glucose tolerance (IGT) and overt
diabetes mellitus are frequently associated with
acromegaly and
hypercortisolism (
Cushing syndrome). The increased cardiovascular morbidity and mortality associated with
acromegaly and
Cushing syndrome may partly be a consequence of increased
insulin resistance that normally accompanies
hormone excess. Acromegalic patients are
insulin resistant, both in the liver and in the periphery, displaying
hyperinsulinemia and increased
glucose turnover in the basal post-absorptive states. The prevalence of
diabetes mellitus and that of IGT in
acromegaly is reported to range 16-56%, whereas the degree of
glucose tolerance seems correlated with circulating
growth hormone (GH) levels, age, and disease duration. Moreover, a family history of diabetes and concomitant presence of arterial
hypertension have been found to predispose to diabetes as well. GH has 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. However, in
acromegaly, increased
IGF-I levels are unable to counteract the
insulin-resistance status determined by GH excess.
Therapy with
somatostatin analogues (SSAs) induce control of GH and
IGF-I excess in the majority of patients, but their inhibitory effect on pancreatic insulin secretion might complicate the overall effect of this treatment on
glucose tolerance.
Hypercortisolism produces
visceral obesity,
insulin resistance, and
dyslipidemia that together with
hypertension,
hypercoagulability, and ventricular morphologic and functional abnormalities increase cardiovascular risk, and persist up to 5 years after resolution of
hypercortisolism.
Hypercortisolism leads to hyperglycaemia and reduced
glucose tolerance, determines
insulin resistance, stimulates hepatic gluconeogenesis and glicogenolisis. In
Cushing syndrome the prevalence of diabetes varies between 20 and 50%, but probably this prevalence is underestimated, as not always an oral
glucose tolerance test is performed in the presence of an apparently normal fasting glycaemia. Again, disease duration, rather than
hormone levels, seems to be the major determinant in the occurrence of systemic complications in
Cushing syndrome. Due to the impact they have on mortality and morbidity in both
acromegaly and
Cushing syndrome, these complications should be treated aggressively. In patients with neuroendocrine tumours (NETs) the occurrence of altered
glucose tolerance may be due to a decreased insulin secretion, like it happens in patients who underwent pancreatic surgery and in those with
pheochromocytoma, or to an altered counterbalance between
hormones, such as in patients with
glucagonoma and
somatostatinoma. Moreover, SSAs represent a valid therapeutic choice in the symptomatic treatment of NETs, and also in this case the medical
therapy of the primary disease, may have a significant impact on the prevalence of
glucose metabolism imbalance. In thyroid disorders, an abnormal
glucose tolerance may be principally encountered in
hyperthyroidism. The pathogenesis is complex and scant data on prevalence and severity are found in the literature. Adequate treatment for
glucose imbalance is mandatory in these peculiar patients in line with the American Diabetes Association and the European Association for the Study of Diabetes consensus statement. In particular, since traditional
insulins have two features that may complicate
therapy (absorption profiles, delayed onset of action and peak activity), the new
insulin analogues could be of particular interest in the management of the secondary diabetes associated with endocrinopathies, considering the
frailty of these patients. Indeed, it has been demonstrated that
insulin glargine, given once daily, reduces the risk of hypoglycaemia compared with other formulations, and can facilitate a more aggressive
insulin treatment in this class of patients.