Table 2.

Disorders to Consider in the Differential Diagnosis of Pituitary Gigantism

Disease NameGenePrevalence of
Pituitary
Disease by Sex		Age of Onset
of GH Excess		Clinically
Evident GH
Excess (%
of Affected
Persons)		Pituitary FindingsExtrapituitary Manifestations
McCune-Albright syndrome 1GNAS 2EqualVariable (~30% diagnosed < age 16 yrs)~20% 3GH-secreting pituitary adenoma or mixed GH- & prolactin-secreting pituitary adenoma &/or hyperplasia of GH- & prolactin-secreting pituitary cellsPolyostotic fibrous dysplasia, café au lait spots, precocious puberty, other manifestations
Multiple endocrine neoplasia type 1 1 MEN1 ↑ Female 4Typically adult-onset; gigantism is rare2%-5%GH-secreting pituitary adenoma, mixed GH- & prolactin-secreting pituitary adenoma; pituitary hyperplasia secondary to a GHRH-secreting neuroendocrine tumor; other pituitary adenoma subtypes can occur: prolactinoma, NFPA, corticotropinoma.Primary hyperparathyroidism, pancreatic neuroendocrine tumors, other manifestations
Carney complex 1PRKAR1A 5EqualTypically adult-onset, but gigantism can occur~10% 6GH-secreting pituitary adenoma or mixed GH- & prolactin-secreting pituitary adenoma &/or hyperplasia of GH- & prolactin-secreting pituitary cells; corticotropinomas described in 2 persons 7Skin hyperpigmentation, myxomas, PPNAD, other manifestations
AIP-related familial isolated pituitary adenoma 8 AIP ↑ MaleTypically 2nd decade of life~80%GH- or mixed GH- & prolactin-secreting pituitary adenoma; pituitary hyperplasia rare; characteristically, can present w/pituitary apoplexy 9; other pituitary adenoma subtypes can occur: prolactinoma, NFPA, corticotropinoma, thyrotropinomaNo
X-linked acrogigantism 8 GPR101 ↑ FemaleEarly onset (in all cases < age 4 yrs)100%Mixed GH- & prolactin-secreting pituitary adenoma &/or hyperplasia of GH- & prolactin-secreting pituitary cells; pituitary apoplexy not describedNo

GH = growth hormone; GHRH = growth hormone-releasing hormone; NFPA = nonfunctioning pituitary adenoma; PPNAD = primary pigmented nodular adrenal disease

1.

Syndromic

2.

McCune-Albright syndrome is caused by early embryonic postzygotic somatic activating mutation of GNAS

3.

Subclinical growth hormone excess has been described.

4.
5.

Approximately 20% of families with Carney complex have been linked to 2p16. 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]; the authors propose that this is a Carney complex-causing gain-of-function variant.

6.

Most patients have subclinical GH excess.

7.
8.

Nonsyndromic

9.

From: X-Linked Acrogigantism

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