Table 4.

Hereditary Cancer Syndromes in the Differential Diagnosis of MEN1

GeneDisorderMOIOverlapping Feature(s)Distinguishing Features
AIP AIP-related pituitary adenoma predisposition (PAP) & multiple types of pituitary adenoma (PITA1) (See AIP Familial Isolated Pituitary Adenomas.)ADPituitary adenomas
  • Earlier-onset pituitary tumors in AIP-assoc PAP than in MEN1
  • MEN1-assoc single pituitary tumors are typically prolactinomas or macroadenomas.
  • AIP-assoc tumors are predominantly GH-secreting adenomas.
GPR101 Pituitary adenoma 2, GH-secreting (PITA2) (OMIM 300943)XLGH-secreting pituitary adenomaNot assoc w/other endocrinopathies typical of MEN1
CDH23 Pituitary adenoma 5, multiple types (PITA5) (OMIM 617540)ADGH-secreting & nonfunctional pituitary adenomas in familial pituitary adenoma types; GH-secreting, nonfunctional, PRL-secreting, ACTH-secreting, TSH-secreting, & plurihormonal (GH & TSH) tumors in sporadic pituitary adenoma typesNot assoc w/other endocrinopathies typical of MEN1
CASR 1
CDC73 2
GCM2
MEN1		Familial isolated primary hyperparathyroidism (FIHP) 3 (OMIM 145980, 145000, 617343)ADParathyroid adenoma or hyperplasiaNot assoc w/other endocrinopathies typical of MEN1. See also Genetically Related Disorders.
CDKN1B Multiple endocrine neoplasia type 4 (MEN4)ADAll featuresNo specific distinguishing clinical features
RET Multiple endocrine neoplasia type 2A (MEN2A)ADPHPT (in ~20%-30% of persons w/MEN2A); hypercalciuria & renal calculi (in some)
  • MEN2A is assoc w/medullary thyroid carcinoma & pheochromocytoma.
  • MEN2A-assoc PHPT is generally milder than MEN1-assoc PHPT.
  • Most persons w/MEN2A & biochemical PHPT do not have clinical symptoms of PHPT.

ACTH = adrenocorticotropic hormone; AD = autosomal dominant; GH = growth hormone; MEN1 = multiple endocrine neoplasia type 1; MOI = mode of inheritance; PHPT = primary hyperparathyroidism; PRL = prolactin; TSH = thyroid stimulating hormone; XL = X-linked

1.

Between 14% and 18% of families with FIHP have identifiable CASR pathogenic variants [Simonds et al 2002, Warner et al 2004]. CASR pathogenic variants have also been identified in individuals with familial hypocalciuric hypercalcemia (OMIM 601198) and neonatal severe primary hyperparathyroidism (OMIM 239200).

2.

Pathogenic variants in CDC73 are associated with hyperparathyroidism-jaw tumor syndrome (see CDC73-Related Disorders). Of note, Warner et al [2004] did not identify any CDC73 pathogenic variants in 22 individuals with familial isolated primary hyperparathyroidism (FIHP).

3.

FIHP is characterized by parathyroid adenoma or hyperplasia without other associated endocrinopathies in two or more individuals in one family.

From: Multiple Endocrine Neoplasia Type 1

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