Endocrine Abstracts

Introduction: RET proto-oncogene is situated on chromosome 10 and encodes a tyrosine kinase receptor. A germline mutation of RET leads to the appearance of MEN 2 syndrome or familial medullary thyroid carcinoma (MTC). One of the most common germline mutation occurs in codon 634. Pheochromocytoma penetrance for codon 634 mutation was demonstrated to increase with age up to 88% by age 77 years.

Aim: To present two familial cases of RET mutation illustrating the different phenotypes that can arise.

Case 1: 44 years old woman who came in our clinic with bilateral hypoechoic thyroid nodules, elevated calcitonin and a slightly raised parathyroid hormone (PTH) with no symptoms. In our center hormonal assessment reflected: calcitonin=861 pg/ml (n=1–11), CEA=76.09 ng/ml. Blood testing for pheochromocytoma and hyperparathyroidism were within the normal range. Fine needle biopsy was performed and the suspicion of MTC (Bethesda V) was confirmed. RET gene analysis showed heterozygous mutation Cys634Trp in exon 11 of RET gene. The patient underwent total thyroidectomy with bilateral jugulo-carotid lymphadenectomy, right upper parathyroidectomy and the diagnosis of MEN 2A was confirmed. We did genetic family screening by evaluating her son (negative for RET mutation) and her father, whose case is detailed below.

Case 2: 73 years old man, with grade II hypertension and chronic gastritis, presented with dizziness, nausea and 5 kg weight loss over 3 months. Computed tomography examination showed right adrenal 16×12 mm nodular formation and a cystic formation of 30×22 mm in the left adrenal gland. Subsequent endocrine evaluation revealed high plasma metanephrines in two consecutive measurements: 237 pg/ml, respectively 291 pg/ml (n=0–100), high cromoganin A, slightly high plasma normetanephrines and a non-suppressed cortisol level after 1 mg of overnight dexametazone. Results of blood testing for hyperparathyroidism and MTC were within the normal range. After performing RET gene analysis, same mutation was confirmed, which guided us to classify the patient into Cluster 2 Adrenal Paraganglioma. The patient underwent preoperatory preparation with doxazosin for laparoscopic right suprarenalectomy.

Conclusion: Screening first-degree relatives for RET mutation is highly recommended because it helps diagnosing adrenal paraganglioma even at average values of hypertension, as well as advanced ages.