GH-induced LH hyporesponsiveness as a potential mechanism for hypogonadism in male patients with acromegaly.

Male patients with acromegaly frequently have hypogonadism. However, whether excess GH affects gonadal function remains unclear. We retrospectively compared clinical features affecting total testosterone (TT) and free testosterone (FT) levels between 112 male patients with acromegaly and 100 male patients with non-functioning pituitary adenoma (NFPA) without hyperprolactinemia. Median maximum tumor diameter (14.4 vs. 26.5 mm) and suprasellar extension rate (33 vs. 100%) were lower in acromegaly, but LH, FSH, TT, and FT were not significantly different. In acromegaly, TT was less than 300 ng/dL in 57%, and FT was below the age-specific reference range in 77%. TT and FT were negatively correlated with GH, IGF-1, and the tumor size, and positively correlated with LH. In NFPA, they were positively correlated with IGF-1, LH, FSH, ACTH, cortisol, and free T4, reflecting hypopituitarism. Multiple regression analysis showed that TT and FT had the strongest correlation with GH in acromegaly, and with LH in NFPA. Surgical remission was achieved in 87.5% of 56 follow-up patients with acromegaly. TT and FT increased in 80.4 and 87.5%, respectively, with a significant increase in LH. In acromegaly, the degree of postoperative increase in TT(FT) correlated with the fold increase of TT(FT)/LH ratio, a potential parameter of LH responsiveness, but not with fold increase of LH, whereas in NFPA it correlated with both. These results suggest that excessive GH is the most relevant factor for hypogonadism in male acromegaly, and may cause impaired LH responsiveness as well as the suppression of LH secretion.

Influence of Short-Term Dietary and Therapeutic Iodine Restriction on the Therapeutic Effects of Radioactive Iodine Therapy in Patients with Graves' Disease.

Background: Several studies have investigated the factors affecting the effects of radioactive iodine (131I) treatment (RAIT) in patients with Graves' disease. However, the influence of dietary or therapeutic iodine on the effect of RAIT has not been fully elucidated yet. The aim of this study was to investigate whether dietary or therapeutic iodine before RAIT influences the therapeutic effects of RAIT with a fixed-dose regimen and a short-term restriction of iodine intake in an iodine-sufficient area. Materials and Methods: We retrospectively analyzed 81 Japanese patients with Graves' disease treated with the following RAIT regimen: dietary iodine restriction for 7 days as well as discontinuation of antithyroid drugs (ATDs), potassium iodine (KI), or both for 5 days before RAIT. On the day of RAIT, we measured urinary iodine content to estimate daily iodine intake. After RAIT, we adjusted the dose of ATDs, KI, or both according to serum thyroid hormone levels every 1-2 months. Using the data from these patients, we investigated the effect of dietary and therapeutic iodine on the therapeutic effects of RAIT. The therapeutic effects at 1 year after RAIT were evaluated based on the necessity of ATDs, KI, or both. Results: Dietary iodine intake was weakly correlated with 131I uptake (RAIU), but the dose of therapeutic iodine was not correlated with RAIU. The therapeutic effects of RAIT were strongly negatively associated with estimated thyroid volume before RAIT. Neither dietary iodine intake nor therapeutic iodine before RAIT affected this association. Conclusion: This study did not find an association between short-term dietary or therapeutic iodine restriction before RAIT and the therapeutic effects of RAIT in an iodine-sufficient area.

Everolimus Directly Suppresses Insulin Secretion Independently of Cell Growth Inhibition.

Everolimus, an orally administered mammalian target of rapamycin inhibitor, has been widely used as an immunosuppressant and an anticancer agent. Whereas everolimus can control recurrent hypoglycemia in patients with insulinoma, possibly through tumor regression and/or the direct inhibition of insulin secretion, time-dependent changes in serum insulin levels caused by everolimus still remain unclear. Here we report a clinical case of a patient with metastatic insulinoma, in which frequent monitoring of serum insulin levels demonstrated rapid and substantial changes in insulin secretion levels, a few days after the discontinuation as well as the readministration of everolimus. To further confirm the direct effect of everolimus on ß-cell function, we performed in vitro experiments using mouse insulinoma cells (MIN6) and human induced pluripotent stem cell (hiPSC)-derived insulin-producing cells and found that everolimus significantly suppressed glucose-stimulated insulin secretion in both MIN6 cells and hiPSC-derived insulin-producing cells. Thus, both a patient with metastatic insulinoma and in vitro experiments demonstrated that everolimus directly suppresses insulin secretion, independently of its tumor regression effect.