From misclassified AIP variant to carney complex: a case report and retrospective evaluation of PRKAR1A in pituitary tumor predisposition.

CONTEXT: Carney Complex (CNC) is a rare multiple endocrine neoplasia syndrome, due to PRKAR1A mutation, that causes GH-secreting pituitary adenomas (PA) in 10% of patients. PRKAR1A is not currently analyzed in patients with isolated sporadic or familial PA, in contrast to MEN1 or AIP.

OBJECTIVE

We report the case of a young man diagnosed with a PA at age 21 during melanoma follow-up, with a family history of PA. He was initially misdiagnosed with FIPA due to a misclassified AIP mutation, before a final diagnosis of CNC was established. We subsequently retrospectively analysed PRKAR1A in a cohort of patients with PA to assess the relevance of includingPRKAR1A in PA predisposition gene panels.

METHODS

After AIP variant reclassification and whole genome analysis of the patient, we performed a retrospective analysis of the genetic and clinical data of patients who underwent germline genetic testing for hereditary predisposition to PA.

RESULTS

Two hundred and twenty patients were included, of whom 16 (7.3%) had a family history of PA, 162 (72.7%) had macro-PA, and 54 (24.6%) had GH- or GH/PRL-secreting PA. Four patients (1.8%) carried pathogenic variants in AIP or MEN1, but none in PRKAR1A.

CONCLUSION

This case underscores the importance of periodically reassessing genetic variants, as reclassification can significantly impact patient management. It also highlights the clinical variability of CNC and the need to screen for CNC features in young patients with acromegaly. Further research is warranted to determine the value ofPRKAR1A testing in isolated GH- and GH/PRL-secreting PA.