Diagnosis and Management of Pheochromocytomas and Paragangliomas: A Guide for the Clinician.

OBJECTIVE: The aim of this review was to provide a practical approach for clinicians regarding the diagnosis and management of pheochromocytomas and paragangliomas (PPGLs). METHODS: A literature search of PubMed was carried out using key words, including pheochromocytoma, paraganglioma, treatment, diagnosis, screening, and management. The discussion of diagnosis and management of PPGL is based on the evidence available from prospective studies when available and mostly from cohort studies, cross-sectional studies, and expert consensus. RESULTS: PPGL are neuroendocrine tumors arising from the chromaffin cells of adrenal medulla and sympathetic and parasympathetic ganglia, respectively. PPGL can be localized or metastatic, and they may secrete catecholamines, causing a variety of symptoms and potentially catastrophic and lethal complications if left untreated. The rarity of these tumors along with heterogeneous clinical presentation often poses challenges for the diagnosis and management. PPGL can be associated with several familial syndromes which are important to recognize. CONCLUSION: The last few years have witnessed an exponential growth in the knowledge around PPGL. This review aims at providing a comprehensive discussion of current concepts for clinicians regarding clinical presentation, diagnostic tools, and management strategies for PPGL.

Simultaneous Occurrence of Germline Mutations of SDHB and TP53 in a Patient with Metastatic Pheochromocytoma.

CONTEXT: We describe a patient with metastatic malignant pheochromocytoma who was found to have germline SDHB and TP53 mutations occurring together. CASE DESCRIPTION: A 39-year-old male presented with neck pain. Magnetic resonance imaging of the neck revealed a C3 vertebral body collapse and an underlying C3 lesion. Computed tomography (CT) of the thorax, abdomen, and pelvis showed multiple skeletal lesions, a sternal mass, bilateral pulmonary nodules, bilateral adrenal masses, and an aortocaval lymph node conglomerate. He underwent biopsy of the sternal mass, which revealed metastatic pheochromocytoma and subsequent blood work showed serum epinephrine levels of 200 pg/mL (normal 10-200 pg/mL), norepinephrine 28 241 pg/mL (normal 80-520 pg/mL), and dopamine 250 pg/mL (normal 0-20 pg/mL). Genetic testing revealed both SDHB and TP53 germline mutations. He was started on α- and ß-blockers and calcium channel blockers to control hypertension and tachycardia. Two months after the diagnosis, a CT of the abdomen and pelvis showed progression of disease, with enlargement of the right adrenal mass as well as the aortocaval conglomeration. His plasma metanephrines were significantly elevated. He was started on systemic chemotherapy with cyclophosphamide, dacarbazine, and vincristine. He required several antihypertensive agents, including metyrosine, to control his blood pressure in preparation for chemotherapy. CONCLUSION: This is the first reported case of simultaneous SDHB and TP53 germline mutations occurring in an individual with a highly aggressive clinical course of pheochromocytoma. We speculate that the simultaneous occurrence of these 2 oncogenic mutations may have led to an aggressive tumor progression.

Chronic maternal calcium and 25-hydroxyvitamin D deficiency in Wistar rats programs abnormal hepatic gene expression leading to hepatic steatosis in female offspring.

Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation. Offspring were fed on control diet post-weaning and studied till 30 weeks. Lipid profile, serum glutamate pyruvate transaminase (SGPT), calcium and vitamin D levels were analyzed. Liver fat deposition, omega-3 fatty acids level and mRNA expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α), sterol regulatory element-binding protein 1c (SREBP-1c), interleukin 6 (IL-6), superoxide dismutase 1 (SOD-1) and uncoupling protein 2 (UCP2) were determined. Low serum vitamin D levels with an increase in SGPT and TG levels in CaD and VDD female offspring were observed. Severe liver steatosis with down-regulation of PPAR-α and UCP2 and up-regulation of SREBP-1c, IL-6 and SOD-1 was observed in the female offspring born to deficient dams. CaD and VDD male offspring showed mild steatosis and down-regulation of UCP2 and SOD-1. We conclude that maternal calcium and vitamin D deficiency programs abnormal lipid metabolism and hepatic gene expression in the F1 generation female offspring leading to hepatic steatosis, despite feeding them on control diet post-weaning.