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

Although fertility is frequently impaired in women with acromegaly, pregnancy is apparently becoming more common due to improvement in acromegaly treatment as well as in fertility therapy. As a result, several studies on pregnancy in patients with acromegaly have been published in recent years adding new and relevant information to the preexisting literature. Also, new GH assays with selective specificities and the knowledge of the expression of the various GH genes have allowed a better understanding of somatotrophic axis function during pregnancy. In this review, we show that pregnancy in women with acromegaly is generally safe, usually with tumoral and hormonal stability. Although the paucity of data limits evidence-based recommendations for preconception counseling and pregnancy surveillance, controlling tumor size and hormonal activity before pregnancy is highly recommended to ensure better outcomes, and surgical control should be attempted when feasible. Treatment interruption at pregnancy confirmation has also proven to be safe, as drugs are not formally allowed to be used during pregnancy. Drug exposure (somatostatin analogs) during early or whole pregnancy might increase the chance of a lower birth weight. Aggressive disease is uncommon and may urge individual decisions such as surgery or drug treatment during pregnancy or lactation.

Detecting and solving the interference of pregnancy serum, in a GH immunometric assay.

BACKGROUND: High homology of GH with placental GH (pGH) and hPL frequently resulted in falsely high GH levels in competitive immunoassays during pregnancy. However, in immunometric assays, falsely high or low GH levels can result from GH-like molecules binding to both or only one monoclonal antibody. Since our GH-IFMA assay detected GH suppression in both normal and acromegalic pregnancies, we evaluated potential negative interference of pregnancy serum in the assay. METHODS: GH was measured in samples from acromegalic patients with and without the addition of normal pregnancy serum using a sensitive in-house two-step GH-IFMA (no crossreactivity with pGH, Prolactin or hPL). Standard GH assay curves were run with and without pGH (20 and 22 K). Pegvisomant, a GH-antagonist with high homology to GH, was also tested for cross-reactivity. RESULTS: Addition of pregnancy serum to acromegaly serum resulted in marked decrease in GH, but addition of pGH did not change GH measurements. Redesign of the routine assay by switching the positions of the antibodies ("inverted" assay) completely abrogated the interference of pregnancy serum. GH by both routine and inverted assays declined progressively throughout pregnancy in controls, with higher nadir levels in the "inverted" assay (median 0.03 µg/L vs 0.50 µg/L, P<0.05). GH suppression during acromegalic pregnancy previously found with the routine assay was not observed in the "inverted" assay. Pegvisomant does not cross-react with GH in the "inverted" assay. CONCLUSIONS: GH measurements in pregnancy by immunometric assays must be made after exclusion of pregnancy serum interference by dilutional tests. Redesigning a two-step immunometric GH assay by switching the positions of the antibodies can be a successful strategy to abrogate such interference.