McCune-Albright Syndrome: Growth Hormone Dynamics in Pregnancy

Abstract

Excess GH secretion has a well recognized association with McCune-Albright syndrome. Although there have been a number of reported pregnancies in uncontrolled acromegaly, none has been described in the McCune-Albright syndrome. We have studied the GH and insulin-like growth factor I (IGF-I) profiles in a patient with confirmed McCune-Albright syndrome and GH hypersecretion throughout a successful pregnancy and postpartum period. Prepregnancy, IGF-I was 60.6 nmol/L (normal, 18.0--43.1), and the daytime GH profile measured using assay A was 9.6--14.0 mU/L. At 13 weeks gestation there was a decline of IGF-I to 33.9 nmol/L and in the daytime GH profile (assay A) to 5.4--6.8 mU/L. At 24 weeks, IGF-I had risen to 51.6 nmol/L. A simultaneous daytime GH profile at this time using assay A revealed levels between 21.3--22.1 mU/L, but only 2.1--3.0 mU/L with assay B. Assay A has significant cross-reactivity with human placental lactogen (HPL), unlike assay B. At 36 weeks, IGF-I was still elevated at 56.6 nmol/L, with a daytime GH profile of 16.6--17.7 mU/L using assay A and 1.5--3.9 mU/L with assay B. At 12 weeks postpartum, IGF-I was 71.4 nmol/L, and the daytime GH profile with assay B was 5.6--8.6 mU/L. These data support a picture of GH suppression during pregnancy in acromegaly associated with McCune-Albright syndrome, shown best with assay B, which discriminates between GH and HPL. These results contrast with previous reports of pregnancy in uncontrolled acromegalics, in whom pituitary GH levels were unaffected by pregnancy, and total GH and IGF-I levels were noted to be elevated. These data suggest that GH secretion in a pregnant acromegalic with the McCune-Albright syndrome may not be entirely autonomous, as seen in classic acromegaly, but may be associated with a degree of negative feedback control that could be exerted by a circulating factor of placental origin, probably HPL or placental GH.

Acromegaly with Fibrous Dysplasia: McCune-Albright Syndrome-Clinical Studies in 3 Cases and Brief Review of Literature-

“…All of our patients had rise in GH in response to TRH. GH dynamics during pregnancy in a patient with acromegaly with MAS has been reported recently [33]. It differs in its lack of autonomicity as compared to classic acromegaly with pregnancy where tumour behaviour is entirely autonomous [33].…”

“…The pathogenesis of hypersecretory endocrinopathies in MAS involves post-zygotic activating mutation of the cAMP-regulating protein, GNAS 1 gene product Gsa, wherein arginine is replaced by other amino acids at position 201 [32,33,35]. This results in the constitutive activation of adenylate cyclase and the subsequent cAMP formation as a second messenger [33,34].…”

MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and pregnancy: a contemporary review

“…That heterogeneity and the different crossreactivities of the assay antibodies for each isoform and different reference preparations used in GH assays explain most of the marked disparity among immunoassay results (25,26,27).…”

“…During pregnancy, measurement of serum GH can lead to spuriously high or low results depending on the crossreactivities of the antibodies with GH-V and the type and design of the assay system (6,9,27). GH isoforms cross-react in most immunoassays, but specific assays for 22K-GH, 20K-GH, for both, and for GH-V have been developed (8,19,28).…”

“…Interference of circulating placental hormones with homology to pituitary GH can often lead to either falsely elevated (27) or suppressed GH values in GH assays (9). Also, usual reference ranges for both basal and post-glucose GH as well as for IGF-1 levels cannot be applied to pregnant women, as pituitary GH levels decline and IGF-1 levels increase during normal pregnancy (20,40).…”