Endocrine Abstracts

JOINT2955

Background: Thyroid carcinoma in patients with pheochromocytoma is 14 times more likely to occur than in general population, however papillary thyroid carcinoma(PTC) has been rarely reported in association with pheochromocytoma. We present the case of a patient diagnosed with synchronous pheochromocytoma and PTC with negative genetic testing for common mutations.

Case report: A 48 years old woman with significant familial history in the oncological field presented to our clinic for a right adrenal nodular lesion accidentally discovered after an abdominal-pelvic CT scan performed for back pain. The endocrine tests revealed increased values of plasma and urinary metanephrines and nonmetanephrines and a right thyroid nodule (TIRADS-4). Fine-needle aspiration biopsy showed atypia of undetermined significance (Bethesda 3). The patient has been subject of right adrenalectomy and subsequent total thyroidectomy. Immunohistochemistry of adrenal tumor showed pheochromocytoma, PASS score=8, suggestive of aggressive tumor behavior, chromogranin A diffuse positivity in the tumor and Ki-67=7%. Thyroid histopathological report revealed unifocal right PTC, pT1bN0, low risk group. The patient was screened for germline mutations by next-generation sequencing (TruSight One Sequencing panel, Illumina) for a panel of 4813 genes including: RET, SDHx, VHL, TMEM, MAX and many other susceptibility genes cited in current literature as being involved in genetic etiology of pheocromocytoma. The analysis could not find any pathogenic or likely pathogenic variants related to the phenotype. Instead, we found a monoallelic missense variant of uncertain significance in a gene for calcium voltage-gated channel subunit 1G, CACNA1G (NM_018896.5): c.1382G>A (p.Arg461Gln). The alpha 1 subunit of the family of T-type low voltage-operated calcium channels (VOCCs) includes three isoforms encoded by the genes CACNA1G (CaV3.1), CACNA1H (CaV3.2), and CACNA1I (CaV3.3). CACNA1H variants have recently been associated with pheochromocytoma (1). The particularity of the case is the association between adrenal paraganglioma and PTC, together with the oncological family history. Although pheochromocytomas secrete mainly catecholamines and their metabolites, they can also secrete many other peptides such as insulin-like growth factor II, that might cause the development and growth of papillary thyroid carcinoma. However these do not explain the family history of various cancers.

Conclusions: The association of PTC and pheochromocytoma in this patient may be coincidental, but it seems more likely to result from genetic variants in genes still awaiting identification.

Reference: 1. Svahn F et al. Genetic variants and down-regulation of CACNA1H in pheochromocytoma. Endocr Relat Cancer. 2024 Jul 8;31(9):e230061.