Differentiated thyroid carcinoma in sporadic and familial presentations of acromegaly: a case series.

Abstract Background: Chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in acromegaly leads to increased morbidities across multiple organs. Differentiated thyroid carcinoma (DTC) has been reported as being a comorbid condition in acromegaly. Acromegaly usually occurs in a sporadic setting and 5% of cases may be due to inherited genetic causes. The most frequent inheritable form of acromegaly is related to germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.  There is limited epidemiological data on the relationship between active acromegaly, its familial forms and DTC. We present the investigation of a FIPA family with homogeneous acromegaly and 6 sporadic acromegaly patients with DTC. Patients and Methods: We undertook a study of 59 acromegaly patients evaluating thyroid nodules by ultrasound and by fine-needle aspiration biopsy following ATA 2015 criteria. We diagnosed 7 differentiated thyroid carcinomas. Resected thyroid carcinoma tissues were stained using an anti-AIP antibody. Analysis of germline and tumor derived DNA for variants in the AIP and MEN1 genes were performed in the FIPA kindred. Results: We describe one FIPA patient and 6 sporadic acromegaly cases with DTC. The FIPA family (AIP mutation negative) consisted of two sisters, one of whom had a DTC with an intermediate risk and incomplete structural response to therapy. In our study DTC in sporadic acromegaly had a low recurrence rate (6/6), and an excellent response to therapy (6/6). IHC for AIP showed similar or increased staining intensity in DTC versus normal thyroid tissue. Conclusion: In our cohort of sporadic and familial forms of acromegaly with DTC, AIP does not appear to influence thyroid cancer progression.