Circadian Variation of Basal Plasma Growth Hormone in Man*

Abstract

Human GH (hGH) circulating during periods of basal pituitary secretion is frequently undetectable in human plasma by RIA. Such basal periods predominate throughout most of the day. Knowledge of the concentration of basal hGH is important, since hGH plays a role in the homeostasis of several metabolic fuels and ions. We have used an immunoad-sorbent technique to extract and concentrate hGH from large plasma samples before RIA in order to precisely measure basal hGH levels [immunoextracted RIA (IERIA)]. Twenty milliliters of blood were drawn from five normal volunteers every 2 h over a 24-h period. The obtained plasma (10–13 ml) was passed over an anti-hGH antibody Sepharose column. The column-bound hGH was eluted and measured by RIA. Recovery of hGH in the plasma extracts was measured using [¹³¹I]hGH as an internal standard. Recovery averaged 54 ± 12% (mean ± sd). Theoretically, the extraction procedure expanded the useful range of the RIA about 50-fold. In practice, the detection limit was 40 pg/ml plasma. Basal hGH (defined as less than 1 ng/ml by conventional RIA) was found to range from less than 40 to 746 pg/ml by IERIA. Above 2 ng/ml, conventional RIA and IERIA yielded comparable results (r = 0.92; P < 0.001), but below 2 ng/ml, the two assays did not correlate (r = 0.01; P > 0.5). In general, conventional RIA overestimated plasma hGH in that range. As a result, the ratio between nocturnal and daytime hGH secretion, as assessed by IERIA, is higher than previously appreciated. We conclude that basal plasma hGH is highly variable below 1 ng/ml, and may on occasion be as low as <40 pg/ml. The episodic nature of hGH release appears to persist in the basal state. The conventional definition for basal hGH (<5 ng/ml) should probably be revised downward to less than 0.8 ng/ml.