Familial isolated pituitary adenoma / AIP-associated pituitary adenoma

AIP-FIPA is inherited in an autosomal dominant manner with incomplete penetrance. Each child of an affected individual has a 50% probability of inheriting the familial pathogenic variant. Predictive testing of asymptomatic at-risk relatives is informative once the familial pathogenic variant has been identified.

The diagnosis of AIP-FIPA is established by molecular genetic testing identifying a germline pathogenic or likely pathogenic variant in AIP. A pituitary MRI is used to detect and characterise the pituitary neuroendocrine tumour, while endocrine evaluation – including assessment of IGF-1, GH (with dynamic testing when indicated), prolactin, pituitary gonadotropins, sex steroids, TSH, free thyroxine, and other pituitary hormone axes as clinically appropriate – defines the functional status of the tumour and associated hypopituitarism. These clinical, biochemical, and radiological findings support the diagnosis but are not specific for AIP-FIPA and do not establish the diagnosis in the absence of a germline AIP pathogenic variant.

Main differential diagnoses include:

• X-linked acrogigantism (X-LAG): female-predominant, infant-onset growth hormone excess; GPR101 duplication
• : pituitary tumours with parathyroid adenoma and gastroenteropancreatic neuroendocrine neoplasms; MEN1
• Carney complex: GH-producing pituitary adenoma with skin pigmentation, myxomas, and primary pigmented nodular adrenocortical disease; PRKAR1A, PRKACB

• Establishing the diagnosis: molecular confirmation ends diagnostic uncertainty and enables genotype-anchored clinical decision-making.
• Surveillance and individualised management: identification of a germline pathogenic variant enables specific and individualised surveillance of asymptomatic variant carriers for emerging pituitary lesions and is a prerequisite for targeted medical care to be initiated by the treating physicians in consultation with the affected individual.
• Family member testing: predictive genetic testing of at-risk biological relatives clarifies their carrier status and informs early detection, reproductive planning, and onwards family counselling.

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