Growth hormone: isoforms, clinical aspects and assays interference

Abstract

The measurement of circulating concentrations of growth hormone (GH) is an indispensable tool in the diagnosis of both GH deficiency and GH excess. GH is a heterogeneous protein composed of several molecular isoforms, but the physiological role of these different isoforms has not yet been fully understood. The 22KD GH (22 K-GH) is the main isoform in circulation, followed by 20KD GH (20 K-GH) and other rare isoforms. Studies have been performed to better understand the biological actions of the different isoforms as well as their importance in pathological conditions. Generally, the non-22 K- and 20 K-GH isoforms are secreted in parallel to 22 K-GH, and only very moderate changes in the ratio between isoforms have been described in some pituitary tumors or during exercise. Therefore, in a diagnostic approach, concentrations of 22 K-GH accurately reflect total GH secretion. On the other hand, the differential recognition of GH isoforms by different GH immunoassays used in clinical routine contributes to the known discrepancy in results from different GH assays. This makes the application of uniform decision limits problematic. Therefore, the worldwide efforts to standardize GH assays include the recommendation to use 22 K-GH specific GH assays calibrated against the pure 22 K-GH reference preparation 98/574. Adoption of this recommendation might lead to improvement in diagnosis and follow-up of pathological conditions, and facilitate the comparison of results from different laboratories.

Pregnancy in acromegaly is safe and is associated with improvements in IGF-1 concentrations

“…During the second half of pregnancy, the placenta increasingly produces placental GH, which shares significant homology with pituitary GH (5,6). Therefore, for interpretation of GH concentrations during pregnancy there is a need to consider the specificity of the assay being used.…”

Laboratory investigations in the diagnosis and follow-up of GH-related disorders

“…It is secreted into the blood stream and mediates its effects via dimerized GH receptors in many tissues. GH in circulation consists of a variety of different isoforms, fragments and molecular complexes (homo-and heterodimers and oligomers) (9). With over 90%, the 22kDa isoform (22,129 Da) is the most abundant isoform, and best reflects total pituitary GH secretion (10).…”

“…Therefore, current guidelines request that modern GH assays should be designed to specifically measure this isoform (4,11). The second most abundant isoform is the 20kDa isoform (20,274 Da), although the biological significance of this isoform has not yet been fully understood (9). In addition, other isoforms with minor chemical modifications exist (10).…”

Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Acromegaly - Part 1: Diagnostic and Clinical Issues

“…The serum growth hormone (GH) and insulin-like growth factor I (IGF-I) should be measured only in the appropriate clinical context (somatic characteristics or specific anamnestic data in the individual patient) [ 17 , 18 ]. It is still unclear whether this evaluation should be performed routinely in all patients with any pituitary adenoma, mostly in PRL-secreting ones.…”

“…Since GH secretion is pulsatile, random GH levels should not be used to diagnose acromegaly [ 21 , 22 ]. In order to facilitate comparability and interpretation, the use of GH assays is now recommended, which are calibrated with the recombinant 22 kDA hGH International Reference Preparation 98/574 [ 18 , 20 ].…”