Malignant Pheochromocytomas/Paragangliomas and Ectopic Hormonal Secretion: A Case Series and Review of the Literature

Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasms defined by the presence of distant metastases. There is currently a relatively paucity of data regarding the natural history of PCs/PGLs and the optimal approach to their treatment. We retrospectively analyzed the clinical, biochemical, imaging, genetic and histopathological characteristics of fourteen patients with metastatic PCs/PGLs diagnosed over 15 years, along with their response to treatment. Patients were followed-up for a median of six years (range: 1–14 years). Six patients had synchronous metastases and the remaining developed metastases after a median of four years (range 2–10 years). Genetic analysis of seven patients revealed that three harbored succinate dehydrogenase subunit B/D gene (SDHB/D) mutations. Hormonal hypersecretion occurred in 70% of patients; normetanephrine, either alone or with other concomitant hormones, was the most frequent secretory component. Patients were administered multiple first and subsequent treatments including surgery (n = 12), chemotherapy (n = 7), radionuclide therapy (n = 2) and radiopeptides (n = 5). Seven patients had stable disease, four had progressive disease and three died. Ectopic hormonal secretion is rare and commonly encountered in benign PCs. Ectopic secretion of interleukin-6 in one of our patients, prompted a literature review of ectopic hormonal secretion, particularly from metastatic PCs/PGLs. Only four cases of metastatic PC/PGLs with confirmed ectopic secretion of hormones or peptides have been described so far.

Influence of hormonal functional status on survival in adrenocortical carcinoma: systematic review and meta-analysis

Objective Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis. Many publications in ACC report on risk factors for a poor outcome; one risk factor studied is hormonal hypersecretion (cortisol, sex-hormones, steroid precursors or aldosterone). The aim of this systematic review was to study the association between hormonal secretion and recurrence or mortality in ACC. Design Systematic review and meta-analysis. We searched PubMed, EMBASE and The Cochrane library (January 2018) for cohort studies examining the association between hormonal secretion on overall or recurrence-free survival in ACC. Methods A random-effects model meta-analysis was performed to obtain a weighted relative risk comparing cortisol-secreting and/or androgen-secreting ACCs to non-secreting tumours regarding overall and recurrence-free survival. Risk of bias assessment was performed for all studies included. Results Nineteen publications were included representing a total of 3814 patients. Most studies were generally considered low/intermediate risk of bias. Meta-analysis showed higher mortality risk for cortisol-secreting ACCs, weighted relative risk 1.71 (95% CI: 1.18–2.47) combining studies that adjusted for tumour stage; also a higher recurrence risk was found for cortisol producing ACCs, relative risk 1.43 (95% CI: 1.18–1.73). Androgen secretion was not clearly associated with survival (RR: 0.82, 95% CI: 0.60–1.12). Conclusion This systematic review and meta-analysis show that cortisol-secreting ACCs are associated with a worse overall survival; future research is needed to establish whether this association points to negative effects of cortisol action, whether it signifies a more aggressive ACC subtype or whether cortisol is merely a prognostic marker.

Some peculiarities in the manifestation of oxidative stress and current status of antioxidant system in adolescents of different age groups with obesity, complicated by insulin resistance and without it

The study has shown that neuroendocrine obesity in adolescents is associated with the formation of oxidative stress which is more pronounced in early than in late puberty. Obesity with concomitant insulin resistance increases manifestations of oxidative stress accompanied by a compensatory increase in the activity of catabolic enzymes and reduced capacity of the defense antioxidant system in late puberty. These alterations may be caused by age-related changes in hormonal secretion under conditions of insulin resistance in late puberty.