Nonfunctional adrenal adenomas and impaired glucose metabolism: a systematic review and meta-analysis.

PURPOSE: Evidence on nonfunctioning adrenal incidentaloma's (NFAI) associated comorbidities and in particular, glucose disorders, is unclear in contrast to adrenal tumors with mild autonomous cortisol secretion. The current systematic review and meta-analysis aimed to assess the burden of impaired glucose metabolism including diabetes mellitus type 2 (T2DM), fasting blood glucose (FBG), and fasting blood insulin (FBI) levels in patients with NFAI and 1-mg overnight dexamethasone suppression test (ODST) ≤ 1.8 µg/dl across published studies. METHODS: We searched PubMed, Cochrane, and Scopus databases for identifying studies published between 1956 and March 2021. Twenty-five studies met the selection criteria including prospective, retrospective, and case-control studies. Two reviewers independently extracted studies, participants' characteristics and outcome data in a total pooled sample of 1548 patients. RESULTS: Patients with NFAI had twofold [(odds ratio (OR) (95% confidence interval (CI)): 2.03 (1.39-2.98)] increased odds to present T2DM as well as higher FBG [weighted mean difference (WMD) (95% CI): 3.85 (1.96-5.74)] and homeostasis model assessment (HOMA) [WMD (95% CI): 0.68 (0.23-1.12)] with respect to controls. On the contrary, the WMD of FBI levels did not differ between the two groups. The incidence of T2DM in a subgroup analysis of patients with NFAI without glucose disorders at baseline was 6% [pooled incidence (95% CI): 0.06 (0.04-0.09)]. CONCLUSIONS: Patients with NFAI and 1-mg ODST ≤ 1.8 µg/dl presented higher odds of T2DM and higher levels of FBG and HOMA index than healthy controls.

Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma.

BACKGROUND: Immune-checkpoint inhibitors have been shown to improve survival in melanoma patients, but can also trigger immune-related endocrinopathies, especially hypophysitis and thyroid dysfunction. METHODS: To assess the incidence and the spectrum of endocrinopathies in melanoma patients treated with immunotherapy a prospective observational study was conducted. Forty out of 339 patients, treated with immune-checkpoint inhibitors, developed endocrinopathies. All patients had hormonal functional tests at screening (before the initiation of immunotherapy) and during follow-up. RESULTS: The total incidence of endocrinopathies was 11.8%, 13.4% due to anti-PD1/PDL1, 5% due to anti-CTLA4, and 18.5% due to sequential and/or combination treatment. Twenty-one patients (6.2%) presented with isolated anterior hypophysitis, eleven (3.2%) with primary thyroid dysfunction and eight (2.4%) with both abnormalities. The most frequent anterior pituitary hormone deficiency was central adrenal insufficiency, followed by central hypothyroidism and hypogonadotrophic hypogonadism. None of the patients with corticotroph axis failure recovered during follow-up. Endocrinopathies occurred after a median of 22 weeks (range: 4-156) from treatment initiation. Of note, sequential and/or combination therapy with anti-CTLA4 and anti-PD1/anti-PDL1 led to an almost threefold incidence of hypophysitis compared to either monotherapy. Only one of 120 patients receiving anti-CTLA4 monotherapy developed primary hypothyroidism. CONCLUSIONS: Our cohort demonstrated an increased incidence of hypophysitis with anti-PD1/anti-PDL1 in contrast to the rarity of primary thyroid dysfunction with anti-CTLA4 treatment. These results could be attributed to genetic/ethnic differences. Sequential treatment is, for the first time to our knowledge, reported to increase the risk of developing hypophysitis to a level as high as that of combination therapy.