Determinants of the growth hormone nadir during oral glucose tolerance test in adults

in European Journal of Endocrinology
Correspondence should be addressed to M Bidlingmaier; Email: martin.bidlingmaier@med.uni-muenchen.de
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Objective

Growth hormone (GH) nadir (GHnadir) during oral glucose tolerance test (OGTT) is an important tool in diagnosing acromegaly, but data evaluating the need to adjust cut-offs to biological variables utilizing today's assay methods are scarce. We therefore investigated large cohorts of healthy subjects of both sexes to define normal GHnadir concentrations for a modern, sensitive, 22 kD-GH-specific assay.

Design

Multicenter study with prospective and retrospective cohorts (525 healthy adults: 405 females and 120 males).

Methods

GH concentrations were measured by the IDS-iSYS immunoassay after oral application of 75 g glucose.

Results

GHnadir concentrations (µg/L) were significantly higher in lean and normal weight subjects (group A) compared to overweight and obese subjects (group B); (males (M): A vs B, mean: 0.124 vs 0.065, P = 0.0317; premenopausal females without estradiol-containing OC (OC-EE) (FPRE): A vs B, mean: 0.179 vs 0.092, P < 0.0001; postmenopausal women (FPOST): A vs B, mean: 0.173 vs 0.078, P < 0.0061). Age, glucose metabolism and menstrual cycle had no impact on GHnadir. However, premenopausal females on OC-EE (FPREOC) exhibited significantly higher GHnadir compared to all other groups (all P < 0.0001). BMI had no impact on GHnadir in FPREOC (A vs B, mean: 0.624 vs 0.274, P = 0.1228).

Conclusions

BMI, sex and OC-EE intake are the major determinants for the GHnadir during OGTT in healthy adults. Using a modern sensitive GH assay, GHnadir concentrations in healthy subjects are distinctly lower than cut-offs used in previous guidelines for diagnosis and monitoring of acromegaly.

Downloadable materials

  • Supplemental table 1. Number of subjects and BMI distribution for the participants classified according to different traditional and arbitrarily
  • Supplemental table 2. Characteristics of subjects with GHnadir concentration  0.4 µg/L.
  • Impact of metabolic factors on GH nadir

 

     European Society of Endocrinology

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Figures

  • View in gallery

    GHnadir concentrations (μg/L), median GHnadir and interquartile range (IQR) in males (M), different phases of menstrual cycle (follicular phase (FP), luteal phase (LP), periovulatory phase, with intake of oral contraception (OC) with gestagen monotherapy (OC-G) or estrogen-containing OC (OC-EE), with the use of hormone-releasing vaginal rings or intra-uterine devices and in postmenopausal women (FPOST). Only selected significance levels shown.

  • View in gallery

    Correlation of GHbasal (μg/L) and GHnadir (μg/L) in all subjects.

  • View in gallery

    Correlation of BMI (kg/m2) and GHnadir concentrations (μg/L) in all subjects. Male: black, premenopausal females without estrogen-containing oral contraception: green, premenopausal females with intake of estrogen-containing oral contraception: orange and postmenopausal women: gray.

  • View in gallery

    Individual fitted points (eLnGHnadir) and 95% confidence interval. Formula: LnGHnadir = -0.866 + (-0.413 × sex) + (0.8282 × OC-EE) + (-0.054 × BMI), sex: 0 = female, 1 = male, OC-EE: 0 = no OC-EE, 1 = OC-EE. (A) males, (B) females without OC-EE, (C) females with OC-EE. BMI, body mass index; OC-EE, estrogen-containing oral contraception.

  • View in gallery

    GHnadir concentrations (μg/L), median GHnadir and interquartile range (IQR) in males (M), premenopausal females without intake of estrogen (EE)-containing oral contraception (OC) (FPRE), premenopausal females with OC-EE intake (FPREOC) and postmenopausal women (FPOST). Red dots indicate subjects with BMI <25 kg/m2.

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