Growth hormone-prolactin-thyrotropin-secreting pituitary adenoma in atypical McCune-Albright syndrome with functionally normal Gs alpha protein.
The McCune-Albright syndrome (MAS) comprises a triad of physical signs: localized bone lesions termed polyostotic fibrous dysplasia, café-au-lait pigmentation of the skin, and autonomous hyperfunction of multiple endocrine systems, including overproduction of GH and T4. A somatic activating point mutation in the gene for the alpha-subunit of the G-protein (Gs alpha) in the affected tissue has been claimed to be the underlying defect. A 29-yr-old patient with MAS, showing polyostotic fibrous dysplasia associated with acromegalic features, underwent endocrinological studies, including oral glucose tolerance test and pituitary stimulation test, and magnetic resonance imaging, revealing elevated plasma concentrations of GH, PRL, and secondary hyperthyroidism due to pituitary macroadenoma infiltrating the sphenoid cavity and extending to the suprasellar space. Subsequently, reduction of tumor mass by a transsphenoidal and a subsequent subfrontal operation led to only marginal amelioration of the excessive hormone production. Postsurgery octreotide and bromocriptine therapy induced near-normalization of hormone concentrations. Immunohistochemistry of tumor tissue confirmed the plurihormonal character, but DNA sequence analysis did not detect any of the two known activating mutations in the Gs alpha gene. Furthermore, biochemical tests revealed normal Gs alpha function, ruling out other mutations that lead to constitutive Gs alpha activation. Our study documents that MAS is a heterogeneous disease. Some, but clearly not all, patients have oncogenic mutations of the gene coding for Gs alpha. Any gene acting down-stream of Gs can theoretically be predicted to result in the same phenotype. In addition, hyperthyroidism of MAS may be secondary to a TSH-producing pituitary macroadenoma.
Third Department of Internal Medicine, University of Vienna, Austria.
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A
Gessl
M
M
Freissmuth
T
T
Czech
C
C
Matula
J A
JA
Hainfellner
M
M
Buchfelder
H
H
Vierhapper
D000236:Adenoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D005121:Extremities / Q000000981:diagnostic imaging; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications* / Q000000981:diagnostic imaging; D019204:GTP-Binding Proteins / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000378:metabolism*; D011859:Radiography; D012016:Reference Values; D013972:Thyrotropin / Q000378:metabolism*
D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases