Table 4.

Syndromes Associated with Pituitary Tumors

Gene(s)DisorderMOIPituitary Tumor FeaturesOther Features
MEN1 Multiple endocrine neoplasia type 1 (MEN1)ADPituitary tumors occur in ~40% of affected individuals, most often prolactinomas
  • Gastro-entero-pancreatic tract tumors
  • Parathyroid adenoma w/hypercalcemia
  • Other manifestations
CDKN1A
CDKN1B
CDKN2B
CDKN2C 		MEN1-like syndrome 1ADPituitary tumors occur in ~40% of affected individuals, most often somatotropinomas
  • Rare disorder
  • Clinical findings similar to those of MEN1
PRKAR1A
PRKACB 2		 Carney complex AD~80% of affected individuals have somatotroph cell hyperplasia or small pituitary adenoma
  • Skin pigmentary abnormalities
  • Myxomas of the organs
  • Schwannomas
  • Primary pigmented nodular adrenocortical disease
  • Large-cell calcifying Sertoli cell tumors
  • Thyroid nodules
  • Acromegaly
GNAS McCune-Albright syndrome NA (somatic)
  • ~30% of affected individuals have pituitary disease
  • Pituitary adenomas w/↑ secretion of growth hormone
  • Hyperplasia of somatomammotroph cells w/prolactinemia
  • Polyostotic fibrous dysplasia
  • Café au lait patches
  • Multiple endocrine disorders (e.g., multinodular goiters, multinodular adrenal hyperplasia, & precocious puberty)
MAX
SDHA
SDHB
SDHC
SDHD
RET 		Hereditary paraganglioma-pheochromocytoma syndromes AD
  • Low penetrance of pituitary disease
  • Pituitary carcinoma described, vacuolated histology picture
  • Paragangliomas
  • Pheochromocytoma
  • GIST
  • Kidney tumors
DICER1 DICER1 syndrome AD
  • Low penetrance of pituitary disease
  • ACTH-secreting pituitary blastoma
Manifests before age 2 yrs
MSH2
MSH6
MLH1
?PMS2 		Lynch syndrome AD
  • Low penetrance of pituitary disease
  • ACTH-secreting macroadenomas
Colorectal, endometrial, ovarian, & other carcinomas
USP8 Pituitary adenoma 4 (OMIM 219090)AD1 individual w/pituitary adenomaDevelopmental delay

AD = autosomal dominant; GIST = gastrointestinal stromal tumor; MEN1 = multiple endocrine neoplasia type 1; MOI = mode of inheritance

1.
2.

One individual with Carney complex (<1% of families with Carney complex) had a germline rearrangement resulting in four copies of PRKACB [Forlino et al 2014]. PRKACB encodes the catalytic subunit Cβ of the cyclic AMP-dependent protein kinase A (PKA). Levels of Cβ and PKA activity were increased in the individual's lymphoblasts and fibroblasts; the authors propose that this is a Carney complex-causing gain-of-function variant.

From: AIP Familial Isolated Pituitary Adenomas

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