Context Mild autonomous cortisol secretion (ACS) is associated with an increased risk of vertebral fractures (VFx). However, the influence of this condition on bone turnover or its association with mild ACS is still controversial. Objective This study aimed to evaluate the impact of mild ACS on bone quality among patients living with the disease. Design and setting A retrospective study was conducted using data from 55 mild ACS and 12 nonfunctioning adrenal tumour (NFT) patients who visited Chiba University Hospital, Japan, from 2006 to 2018. Patients and main outcome measures We analysed clinical features and bone‐related factors, including bone mineral density (BMD) and VFx, performed blood tests to assess bone metabolism markers in patients with mild ACS and NFT, and assessed the associations between bone‐related markers and endocrinological parameters in patients with mild ACS. Results No significant differences between mild ACS and NFT patients were observed with respect to the presence or absence of VFx and BMD. Urinary free cortisol (UFC) was higher in mild ACS patients with VFx than those without (p = .037). The T‐score and young adult mean (YAM) of the BMD of the femoral neck in mild ACS patients with a body mass index <25 were positively correlated with dehydroepiandrosterone sulphate levels (ρ: 0.42, p = .017; ρ: 0.40, p = .024, respectively). Pearson's correlation analysis showed that bone‐specific alkaline phosphatase was negatively correlated with UFC in the patients with mild ACS (ρ: −0.37, p = .026). Conclusions These results suggest that urinary free cortisol may be useful for predicting bone formation in mild ACS patients.

Purpose Growth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies including secondary adrenal insufficiency (AI). A growth hormone-releasing peptide-2 (GHRP2), which is wildly used for the diagnosis of patients with GHD, has been considered to induce not only growth hormone (GH) release but also ACTH release. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear. Methods The GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests and/or insulin tolerance tests (ITTs) were performed on 36 patients having hypothalamic-pituitary disorder. Results Twenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cut-off value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cut-off value (1.55-fold and 10 µg/dl, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI. Conclusion We recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking and delays in diagnosis of secondary AI that frequently accompanies GHD.

Introduction: Although 18F-FDG PET was originally developed to evaluate benign and malignant tumors, the frequency of detection of benign adrenocortical adenomas showing FDG-PET accumulation has increased. However, the details of FDG-PET-accumulated benign adrenocortical adenomas have not been elucidated. Methods: To elucidate the pathophysiology of FDG-PET-positive cortisol-producing adrenal tumors, we performed clinicopathological and genetic analyses of adrenocortical adenomas examing FDG-PET in 30 operated patients with unilateral cortisol-producing adrenal tumors (26 adrenal adenomas and 4 adrenal cancers). Results: All adrenocortical carcinomas and 17/26 (65%) benign adrenocortical adenomas showed high FDG accumulation (SUVmax ≥ 3). In adrenocortical adenomas with high FDG accumulation (SUVmax ≥ 3), SUVmax showed a positive correlation with the CT Hounsfield units. A higher SUVmax showed a clear black adenoma appearance with predominantly compact cells, which exhibited high T1 and T2 signals, a lack of signal drop on out-of-phase imaging on MRI, and less accumulation on 131-I adsterol scintigraphy. Furthermore, RNA-sequencing analysis revealed significant increases in the lysosomal and autophagy pathways and metabolic pathways, including glycolysis through glucose transporter (GLUT) 1 and 3, in black adenomas with high-level FDG accumulation. Discussion: A black adenoma is blackish due to lipofuscin, which accumulates as a result of damaged mitochondria or proteins that escape lysosomal degradation or autophagy. Since FDG in PET is taken up via GLUTs, alteration of the intracellular metabolic dynamics associated with mitochondrial damage in black adenomas may increase PET accumulation. Conclusion: Black adrenal adenomas should be considered with adrenal tumors showing PET accumulation and low lipid contents.