Table 4.

Somatic and germline genetic causes of pituitary adenomas

	Gene	Phenotype	Pituitary features
Germline	AIP	~20% of FIPA	Younger age (<30 years)
		~13% of young sporadic macroadenomas ~23% of pediatric pituitary adenomas ~29% of gigantism	Male predominance Large invasive adenomas
	GPR101(mosaicism in sporadic males)	X-LAG syndrome 10% of gigantism	Early onset (<36 months) Acromegaly features Increased appetite Hyperprolactinemia Hyperplasia
	MEN1	Up to 50% have pituitary adenoma	Mainly prolactinomas Plurihormonal and multiple adenomas Female predominance Larger and more invasive
	CDKN1B	~37% of MEN4 have pituitary adenoma	All subtypes
	PRKAR1A	Pigmentations, myxomas, hormone hypersecretion	Up to 12% have acromegaly
	PRKACB		Multiple adenomas with surrounding hyperplasia
	SDHx, SSDHA, SDHB, SDHC, SDHD, SDHAF2	~30% have pheochromocytoma and/or paraganglioma and pituitary adenoma	Prolactinomas, somatotrophinomas, nonsecreting adenomas Extensive cytoplasmic vacuolization Mostly aggressive macroadenomas
	MAX	3PAs Aggressive pheochromocytoma	Prolactinomas, somatotrophinomas
	NF1	Neurofibromatosis type 1	Acromegaly or gigantism
	DICER1	Pleuropulmonary blastoma	Cushing’s disease with high mortality in early infancy
	CABLES1	Corticotrophinomas	Invasive macroadenomas with high Ki-67 index
Somatic	GNAS	30-60% of somatotrophinomas	Smaller, densely granulated, older age
		McCune-Albright syndrome (café-au lait macules, fibrous dysplasia, endocrine hyperactivity)	10-15% acromegaly and/or gigantism Pituitary hyperplasia
	PIKA3CA	All types	Mainly large adenomas
	USP8	30-60% of corticotrophinomas	Female predominance
	USP48	~20% of USP8 WT corticotrophinomas	No difference vs WT
	BRAF	~16% of USP8 WT corticotrophinomas	Higher ACTH and cortisol

Abbreviations: 3PAs, pituitary adenomas, paragangliomas, and pheochromocytomas; FIPA, familial isolated pituitary adenoma; WT, wild-type; X-LAG, X-linked acrogigantism. Adapted with permission from Vandeva et al. (2019) (187).