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Most cases of hypertension are because of essential hypertension, however 5% - 15% of cases can be a result of a secondary cause. In this article, we focus on the endocrine causes of secondary hypertension with a particular focus on pheochromocytomas (PCCs) and paragangliomas (PGLs). Around 15 endocrine disorders can initially present with hypertension. Amongst those PCCs and PGLs are rare but potentially life-threatening causes. An early diagnosis and timely referral can be life-saving. Herein, we present an approach for screening and diagnosis of these patients and focus on the importance of genetic testing.

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla chromaffin cells, usually associated with features of catecholamine excess. Clinically and biochemically silent pheochromocytoma without adrenergic symptoms or elevated catecholamine concentrations are rare. A 71-year-old female presented with acute right flank pain with abdominal computed tomography (CT) scan revealing a hemorrhagic right adrenal mass. She had no preceding adrenergic symptoms, and normal serum electrolytes, on a background of well-controlled hypertension on amlodipine monotherapy. After conservative management and discharge, an outpatient CT adrenal scan confirmed an 88 × 64 mm right adrenal mass demonstrating intense avidity (maximum standardized uptake value, 20.2) on fluorodeoxyglucose F 18-positron emission tomography (FDG-PET)/CT scan. Biochemical screening supported a nonfunctional adrenal lesion with normal-range plasma normetanephrines and metanephrines. She underwent a right adrenalectomy for presumed nonfunctioning adrenocortical cancer; however, histopathology demonstrated a 120-mm pheochromocytoma. Succinate dehydrogenase subunit B (SDHB) and fumarate hydratase (FH) staining were retained; however, weakly positive 2SC staining raised concerns for FH-deficient pheochromocytoma. Germline DNA sequencing was negative for pathogenic RET, VHL, SDHB, SDHD, or FH variants. Tumor cells stained positive for tyrosine hydroxylase and negative for dopamine β hydroxylase. Four months postoperatively, progress FDG-PET/CT scan demonstrated no focal avidity. Massive biochemically silent pheochromocytomas are exceedingly rare, and we discuss various mechanisms that may predispose patients to this phenomenon. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]