Effects of growth hormone replacement therapy on levels of cortisol and cortisol-binding globulin in hypopituitary adults

Tschöp, Matthias H.; Lahner, Harald; Feldmeier, H; Grasberger, Helmut; Morrison, KM; Janßen, OE; Attanasio, AF; Strasburger, C. J.

doi:10.1530/eje.0.1430769

Cited by 28 publications

(17 citation statements)

References 18 publications

(12 reference statements)

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“…Ghrelin was administered as a single intravenous dose in humans in these studies and as either a single injection or continuously over several hours in the animal models. The longest studies in animals with ghrelin involve ghrelin administration either continuously or intermittently for a week (51,55). However, in one patient with a malignant ghrelinoma and high ghrelin levels, levels of GH, IGF-I, cortisol, TSH, total T 3 , FSH, and LH were well within the normal range (57), raising the question whether effects of short-term exogenous ghrelin administration on the endocrine system differ from those of endogenous chronic ghrelin concentrations.…”

Section: Discussionmentioning

confidence: 99%

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Misra¹,

Miller²,

Kuo³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

151

132

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Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P ϭ 0.002), nadir (P ϭ 0.0006), and valley levels (P ϭ 0.002). On deconvolution analysis, secretory burst amplitude (P ϭ 0.03) and burst mass (P ϭ 0.04) were higher in AN, resulting in higher pulsatile (P ϭ 0.05) and total ghrelin secretion (P ϭ 0.03). Fasting ghrelin independently predicted GH burst frequency (r ϭ 0.44, P ϭ 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency. growth hormone; cortisol; total triiodothyronine; estradiol; luteinizing hormone; insulin resistance GHRELIN, A 28-AMINO ACID PEPTIDE, is a growth hormone (GH) secretagogue (2, 4, 25, 26, 50 -53) that is also orexigenic (40,56). It is unknown whether elevated ghrelin values are an important contributing factor to the elevated GH levels that occur in anorexia nervosa (AN), a unique model of chronic undernutrition. We have demonstrated higher fasting ghrelin levels in adolescent girls with AN compared with healthy adolescents and higher nadir ghrelin levels following an oral glucose load (36). Girls with AN also have higher GH concentrations, a consequence of increased basal GH secretion and secretory burst frequency (33). Similarly, elevated ghrelin (21, 39) and GH concentrations (47, 49) have been reported in adult women with AN. Negative feedback from low IGF-I levels has been hypothesized to cause increased GH secretion, and the relationship between ghrelin and GH secretion in AN has not been explored.Administration of a single dose of intravenous ghrelin causes an increase in GH secretion in both rodent models (51, 66) and healthy adults (4, 50, 52). Howe...

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Section: Discussionmentioning

confidence: 99%

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Misra¹,

Miller²,

Kuo³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

151

132

View full text Add to dashboard Cite

show abstract

“…Several studies suggest that the maximal change in hormone levels occurs approximately 6 weeks after the start of GH treatment [3, 28]and exists both in hypothyroid and euthyroid patients [29, 30]. Thyroxine-binding globulin and SHBG were not affected by GH replacement, thus the therapy may not alter the transport/binding of the thyroid hormones [31]. The bioavailability, however, can be changed, for example by increased T 4 to T 3 conversion.…”

Section: Discussionmentioning

confidence: 99%

“…Both increased [9], unchanged [17]and reduced – when administering higher GH dose [44]– basal or ACTH-stimulated glucocorticoid levels have been reported during GH treatment. Inhibition of 11β-HSD-1 and increase in the clearance of cortisol has been speculated to precipitate secondary adrenal failure after the initiation of GH replacement therapy [31]. There may be changes in local tissue cortisol exposure, which are not manifest by measuring circulating cortisol concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with partial or total ACTH deficiency, in whom cortisol replacement is suboptimal, may be at risk of clinical manifestation of cortisol deficiency when they are commenced on GH therapy [42, 45]. The pharmacokinetics of cortisol is not altered [31], but the cortisol-binding globulin is decreased [31, 41]during GH replacement therapy. The unchanged cortisol response to ACTH reported in our study suggests that in ACTH-deficient individuals the adrenal reserve might be normal or perhaps down-regulated, because the required dose of hydrocortisone had to be increased in only 1 out of 66 patients with secondary cortisol deficiency, and in only 2 out of 24 patients with intact pituitary-adrenal axis hydrocortisone replacement therapy was initiated.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Growth Hormone Replacement Therapy on Pituitary Hormone Secretion and Hormone Replacement Therapies in GHD Adults

Hubina¹,

Mersebach

Rasmussen

et al. 2004

Horm Res Paediatr

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Objective: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes. Methods: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy. Results: In the placebo-controlled trial, the FT₃ levels increased after 6 months in the GH-treated group, and in the open study the FT₃ levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction. Conclusion: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients.

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“…Growth hormone inhibits 11βHSD1, but does not affect 11 βHSD2. Another effect of GH on cortisol metabolism is the decrease of cortisol binding globulin level which lowers total cortisol while free cortisol level remains stable [25].…”

Section: Discussionmentioning

confidence: 99%

Remission of Cushing's disease with growth hormone replacement

Öztürk

Atmaca

2011

Growth Hormone & IGF Research

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Effects of growth hormone replacement therapy on levels of cortisol and cortisol-binding globulin in hypopituitary adults

Cited by 28 publications

References 18 publications

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Effect of Growth Hormone Replacement Therapy on Pituitary Hormone Secretion and Hormone Replacement Therapies in GHD Adults

Remission of Cushing's disease with growth hormone replacement

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