Endocrine Abstracts

Introduction: Parathyroid carcinoma (PC) is one of the rarest endocrine malignancies. Most PCs are sporadic, sometimes occurring in the framework of familial primary hyperparathyroidism (PHPT). PHPT due to PC is usually characterized by significantly increased PTH levels, severe hypercalcemia, larger tumor size and a higher incidence of disease complications.

Clinical case: A 56-year-old male C. presented with an accidental formation at the posterior contour of the right thyroid gland lobe 10х9х9 mm according to US in 2017 (correlated with ST scan). Mineral metabolism parameters were assessed for the first time after a year: PTH 13.67 pmol/l (1.6-6.9), hypercalcemia - Ca 2.86 mmol/l (2.12-2.6), P and daily calciuria were not determined. PHPT complications included recurrent urolithiasis (first manifesting at age 25), osteopenia in L1-L4 (-2.2 SD T-score). C. did not notice loss of height, gastric and duodenal ulcers. There was no family history. In 2019 the patient underwent selective parathyroidectomy followed by mild asymptomatic hypocalcemia (Ca 2.15 mmol/l). At discharging he was prescribed cholecalciferol 2000 IU. Histological examination revealed atypical parathyroid tumor (APT) with fibrous bands, hemorrhages and foci suspicious for capsular invasion. After immunohistochemistry (IHC) the diagnosis was reclassified as PC based on capsular invasion and the presence of tumor cells in the surrounding fatty tissue. Ki-67 was 9%, there was positive parafibromin expression. Regular follow-up confirmed normocalcemia and PTH within the reference ranges. We recommended gene panel sequencing associated with hereditary forms of PHPT that revealed heterozygous mutations with uncertain significance variants: in the RET (c.3052C>T:p.L1018F) and CYP24A1 (c.37G>A:p.A13T) genes. The patient is currently in remission of the disease. DEXA scans showed positive dynamics in the BMD (L1-L4 -1 SD) There are no clinical symptoms of MEN2 syndrome. Liquid chromatography–mass spectrometry did not reveal any changes in the vitamin D metabolites similar to CYP24A1 mutation.

Conclusions: Patients with solid masses near the typical location of the parathyroid glands should be examined for PTH and Ca. Morphological diagnosis of ATP requires additional IHC. In the present case the mild clinical course of PC and tumor’s small size are noteworthy. The identified mutations with unknown pathogenicity are also of particular interest because they have not been previously described in patients with PC.