Simultaneous presentation of giant pheochromocytoma, primary hyperparathyroidism, and mixed-medullary–papillary thyroid cancer in MEN 2A
A 40-year-old, married man, having five children, fifth of eight siblings, was referred to our tertiary care referral centre, with the complains of persistent headache and palpitations (at rest), that had increased since the last 2 months, on the background of hypertension (14 years) and a single episode of renal calculi 7 years ago. His treating physician admitted him at a local hospital for difficult-to-control severe hypertension and undertook a computed tomography (CT) scan of the abdomen, which revealed a mass in the abdomen. He was then subsequently referred to the surgical department with the aim of removing the mass. The surgeons on suspecting an underlying catecholamine secreting adrenal mass, referred the patient to our endocrine team for further evaluation. Family history suggested hypertension in three of his siblings. His parents expired at a young age. He was a nonsmoker, nonethanolic, on the following antihypertensive medication (calcium-channel blocker, angiotensin converting enzyme inhibitor, and beta-blocker).\nExamination revealed a young man with weight of 70 kg, body mass index 23.5 kg/m2, pulse 100 beats/minute and a blood pressure 160/100 mm of mercury pressure supine, without any postural fall. Systemic examination revealed a mass in the region of the left thyroid gland that was firm without obvious lymphadenoapthy. There was no other significant finding of note.\nWe considered workup for a possible catecholamine secreting pathology associated with a thyroid mass in a young patient.\nBiochemistry revealed normal blood counts, blood film, liver function tests (albumin 4.5 g%); impaired renal function (creatinine 1.71 mg%, urine routine + protein); hyperuricemia (uric acid 10.2 mg%), hypomagnesemia (1.4 mg%); impaired fasting glucose (oral glucose tolerance test 75 g: 0 hours 108 mg% 1 hour 201 mg% 2 hours 138 mg%) and parathormone-dependent hypercalcemia [calcium 13.8 mg/dl, corrected calcium 13.4 mg/dl, inorganic phosphorous 1.7 mg/dl, alkaline phosphatase 140 IU/l (50-136), parathormone 326 pg/ml (10-69), vitamin D3 11.2 nmol/l (11-42)].\nThe patient was euthyroid [Ft4 1.1 ng/dl (0.9-1.7) Ft3 2.8 ng/dl TSH 0.76 mIU/ml (0.4-5)] with 9 am adrenocorticotrophic hormone (ACTH) 31 pg/ml (0-46 pg/ml), 9 am cortisol 23 mcg/dl; midnight cortisol 1.6 mcg/dl (collected within 10 minutes of awakening) and normal overnight dexamethasone suppression test (9 am cortisol 0.9 mcg/dl).\nTumor markers, thyroglobulin 1980 ng/ml (<33), calcitonin 590 pg/ml (<18.2) and carcinoembryonic antigen 15.31 ng/ml (<5) were elevated suggesting possible medullary carcinoma of thyroid. Twenty-four-hour urinary metanephrines 4810 mcg/day (0-350 mcg/day) and normetanephrines 3660 mcg/day (0-650 μg/day) were significantly elevated suggesting catecholamine secreting tumor.\nAn echocardiogram showed a reduced left ventricular ejection fraction of 40%.\nCT scan whole body: [] revealed a 16.4 cm × 14 cm mass with multiple hypodense areas of necrosis in the left para and suprarenal area, compressing and displacing the left kidney []; multiple bilateral renal calculi (largest 2.4 cm × 1.3 cm in the left kidney); mild left-sided hydronephrosis and a 3.4 cms mass in the left lobe of the thyroid.\nDoppler ultrasound of neck: [] showed a 4 × 3.7 × 3 cm mass in the left lobe of thyroid.\nTc thyroid uptake scan: Enlarged left lobe of thyroid with cold nodule in the left lobe and isthmus.\nSESTAMIBI: Localized to the thyroid mass with a brisk wash out, ruling out a parathyroid lesion. This however was on the background of a parathormone-dependent hypercalcemia.\nThe imaging confirmed a thyroid mass, but localizing studies for a parathyroid adenoma or hyperplasia was unrewarding.\nThe patient's calcium was corrected using fluid resuscitation with diuretic cover and pamidronate. Calcitonin was used in a single dose before we realized that the patient had a possible medullary thyroid carcinoma. Fortunately the blood for serum calcitonin was analyzed in a sample that was collected prior to administering calcitonin. He was rendered normocalcemia prior to pheochromocytoma surgery.\nHe was alfa blocked using intravenous phenoxybenzamine for 3 days and volume resuscitated before surgery. An adrenal mass weighing 1.8 kg was removed. The postoperative course was complicated by acute tubular necrosis. During this time he was conservatively managed while keeping a close eye on his serum calcium. His blood pressure had normalized and was off all antihypertensives. Histopathology confirmed pheochromocytoma [].\nHistopathology of adrenal mass showed alarge circumscribed tan tumor weighing 1.836 kg []. Cut surface was fleshy, friable, tan-coloured with cystic spaces containing foci of hemorrhage consistent with pheochromocytoma. The immunohistochemistry profile was strongly positive for synaptophysin, chromogranin A, and S-100.\nOn the eighth postoperative day, surgery addressing of the parathyroids and thyroid was planned. The surgeon undertook a total thyroidectomy and removed all the parathyroid glands. Frozen section confirmed by histopathology revealed parathyroid hyperplasia [] and medullary carcinoma of the thyroid [].\nHistopathology of the thyroid showed a 4 × 3.7 × 3 cm gray white firm tumor [] replacing most of the thyroid parenchyma. Microscopy was consistent with medullary thyroid carcinoma mixed with papillary thyroid carcinoma [, ].\nPostoperatively the patient became hypocalcemic requiring 2 days of intravenous calcium therapy. A repeat calcitonin done on the seventh postoperative day was 17.8 pg/ml, ensuring adequacy of surgery. The patient was finally discharged with a follow-up to discuss genetic counseling; however he denied any further assistance and was lost to follow-up.