Endocrine Abstracts

Purpose: D631Y is a rare mutation associated with MEN2a in which there is an aspartic acid to tyrosine amino acid substitution at codon 631 in exon 11. Common clinical features of this variant of RET mutation are pheochromocytoma in 50%, medullary carcinoma in 30%, primary hyperparathyroidism is very rare. We present the patient harboring RET D631Y mutation.

Clinical case: In April 2017 40-year-old woman was admitted to endocrine department of the Almazov Centre, she presented with paroxysmal hypertension and headaches. She had history of paroxysmal hypertension since age 29. At the age 31 left adrenal pheochromocytoma was revealed and operated on. The diagnosis was confirmed by the pathology. After surgery the blood pressure (BP) normalized. At the age 39 hypertensive crises resumed. In 2017 her blood metanephrine and normetanephrine were elevated: 192.7 pg/ml (0–65), 479.3 pg/ml (0–196) respectively, Chromogranin A level was slightly elevated 127.27 μg/l (0–100), 24-h urinary metanephrines were high: 0.167 μg/day (0–0.04). Abdominal CT demonstrated two right adrenal lesions 1.6×1.5×2.4 sm and 2.7×1.5×2.2 sm. 123I-MIBG scanning showed increased uptake in the right adrenal. Patient’s calcitonin level was normal 4.59 pg/ml (0–5), as well as total calcium (2.53 mmol/l (2.15–2.65)), parathyroid hormone (65.21 pg/ml (15–65)). No thyroid nodules were found with the ultrasound examination (US). Right adrenalectomy was done in May 2017. Pathology examination confirmed the pheochromocytoma, immunnohistochemistry staining revealed the STTR2 expression. After surgery BP became normal. In April 2017 genetic testing was recommended, NGS was performed and RET D631Y mutation was found. These results were obtained in December 2017. At that time blood metanephrine was 11.2 pg/ml (0–65), blood normetanephrine was 207.4 pg/ml (0–196), chromogranin A was normal, calcitonin was 8.6 pg/ml (3–19). In January 2018 patient was re-examined: 24-h urine metanephrine level was 0.003 mg/l (0–0.04), total calcium and parathyroid hormone were at normal range. Slight calcitonin elevation was identified: 8.25 pg/ml (<5). Thyroid US revealed a small nodule 0.46×0.37 sm. Pentagastrine was not available, but considering the results of genetic testing total thyroidectomy was recommended to the patient.

Conclusion: Present report supports the relevance of RET testing in patients with pheochromocytoma even if the basal calcitonin over long period of time since the detection of adrenal tumor is normal. Prompt RET mutation diagnosis allows to choose the correct treatment strategy and timely conduct the thyroidectomy.