Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate

textabstractIntroduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis. Results: Four hundred seventy-nine patients received a total of 1,693 administrations of177Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after the first cycle of177Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas); and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered. Conclusion: Hormonal crises after177Lu- octreotate therapy occur in 1% of patients. Generally,177Lu- octreotate therapy is well tolerated

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