Endocrine Abstracts

Background: MEN1-related primary hyperparathyroidism (PHPT) characterised by benign course, whereas malignant transformation is extremely rare. The diagnosis of parathyroid carcinoma (PC) within the MEN-1 syndrome is a challenge for a range of specialists.

Clinical case: A 47-year Eastern European female. PHPT had been revealed during examination for multinodular goitre: PTH 614 nmol\l, calcium 3.06 mmol\l. Results of imaging methods were controversial (multiple lesions). The patient underwent total thyroidectomy and parathyroidectomy. Histological and immunohistochemical (IHC) examinations confirmed parathyroid carcinoma with the vascular and capsular invasion, spread to adjacent adipose tissue ??1N???Pn0LV, positive for PTH and Chromogranin A. The other parathyroid glands were described as adenomas. At the same time a neuroendocrine tumour of the lung (NET) 32×27×30 mm. (G2) was revealed. The patient refused surgery and further was treated with lanreotide 120 mg every 28 days. Hypercalcemia, hypercalciuria and low level of PTH were detected four years after primary surgery herewith she did not receive calcium and active vitamin D supplements. Bone scintigraphy excluded the osteoblastic process. 68Ga-DOTA-TATE PET/CT showed a lung tumour with increased growth up to 49×45 mm. IHC analysis of the bronchoscopic samples confirmed the highly differentiated lung NET expressing PTH. There was genetic screening at the age of 52 revealing mutations in the MEN1 (1308G>A ?.W436X(NM_130799.2, pathogenic) and RET genes (HG38, chr10:43105062C>T, c.736C>T, with unknown clinical significance). The same MEN1-mutation was identified in her daughter, who was diagnosed with PHPT (parathyroid adenoma) and non-functioning pituitary microadenoma. Other components of syndrome manifested consistently. At the age of 50 she was diagnosed with pancreatic head tumour 31×34 mm, treated first with etoposide, carboplatin. Later pancreas body NET (19×13 mm., SUV=6.64), tail (11×9 mm., SUV =23.28 and 15×12 mm., SUV 15.22) were visualised on PET/CT. Pituitary macroadenoma 5.5×15×10 was identified at the age of 51. Due to an elevated level of IGF-1 and the absence of a decrease of tumour size, lanreotide dose had been increased to 120 mg every 21 days with the addition of cabergoline 0.5 mg once a week. The conservative treatment and follow-up are ongoing.

Conclusion: This case demonstrates the atypical genetic background in a patient with MEN-1 and PC. Despite the presence of RET mutation, components of MEN-2 syndrome were not confirmed. The revealed hypercalcemia and hypercalciuria accompanied by suppressed iPTH allow us to assume the ectopic production of parathyroid hormone-related protein in the lung NETs.