The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults

Weaver, Jolanta U.; Thaventhiran, L; Noonan, Kate; Burrin, Jacky M.; Taylor, Norman; Norman, M. R.; Monson, John P.

doi:10.1111/j.1365-2265.1994.tb01830.x

Cited by 119 publications

(105 citation statements)

References 32 publications

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“…However, both treatments are also known 11b-HSD1 inhibitors (Stewart et al 2001, Hellmich et al 2013, indeed metyrapone-mediated inhibition of 11b-HSD1 is postulated to contribute to improved memory consolidation and retrieval in rodent studies (Hellmich et al 2013). Furthermore, GH-deficient (and subsequently IGF1-deficient) patients exhibit increased global 11b-HSD1 activity (Weaver et al 1994) and a skin phenotype characterized by epidermal thinning (Lange et al 2001). This is also a common phenotype of aged skin, which we found to display elevated 11b-HSD1 activity in both humans and mice (Tiganescu et al 2013) while circulating GH/IGF1 levels are also known to decline with advancing age.…”

Section: Discussionmentioning

confidence: 62%

Increased glucocorticoid activation during mouse skin wound healing

Tiganescu

Hupe

Uchida

et al. 2014

Journal of Endocrinology

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Glucocorticoid (GC) excess inhibits wound healing causing increased patient discomfort and infection risk. 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in rodents) in many tissues including skin, where de novo steroidogenesis from cholesterol has also been reported. To examine the regulation of 11b-HSD1 and steroidogenic enzyme expression during wound healing, 5 mm wounds were generated in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to unwounded skin. 11b-HSD1 expression (mRNA and protein) and enzyme activity were elevated at 2 and 4 days post-wounding, with 11b-HSD1 localizing to infiltrating inflammatory cells. 11b-HSD2 (GC-deactivating) mRNA expression and activity were undetectable. Although several steroidogenic enzymes displayed variable expression during healing, expression of the final enzyme required for the conversion of 11-deoxycorticosterone to corticosterone, 11b-hydroxylase (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11-deoxycorticosterone was the principal progesterone metabolite in mouse skin before and after wounding. Our findings demonstrate that 11b-HSD1 activates considerably more corticosterone than is generated de novo from progesterone in mouse skin and drives GC exposure during healing, demonstrating the basis for 11b-HSD1 inhibitors to accelerate wound repair.

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Section: Discussionmentioning

confidence: 62%

Increased glucocorticoid activation during mouse skin wound healing

Tiganescu

Hupe

Uchida

et al. 2014

Journal of Endocrinology

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“…57 Three subjects had a peak cortisol of > 550 nmol/l in response to an insulin tolerance test; the other 16 subjects were treated with hydrocortisone. They participated in a 6-month double-blind placebo controlled trial of GH treatment, with a 6-week washout phase.…”

Section: Interactions With Other Hormone Replacement Therapy and Medimentioning

confidence: 99%

Why is the management of glucocorticoid deficiency still controversial: a review of the literature

Crown

Lightman

2005

Clinical Endocrinology

116

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SummaryAll endocrinologists would like to make glucocorticoid replacement therapy for their hypoadrenal patients as physiological as possible. Many would like the reassurance of a method of monitoring such treatment to confirm that they are achieving this aim. Advances in our knowledge of the normal physiology are relevant to our attempts to do this. The cortisol production rate in normal subjects is lower than was previously believed. The normal pattern of glucocorticoid secretion includes both a diurnal rhythm and a pulsatile ultradian rhythm. Glucocorticoid access to nuclear receptors is 'gated' by the 11-β -hydroxysteroid dehydrogenase enzymes, which interconvert active cortisol and inactive cortisone. Such complexities make the target of physiological glucocorticoid replacement therapy hard to achieve. The available evidence suggests that conventional treatment of hypoadrenal patients may result in adverse effects on some surrogate markers of disease risk, such as a lower bone mineral density than age-sex matched controls, and increases in postprandial glucose and insulin concentrations. Although the quality of life of hypoadrenal patients may be impaired, there is no evidence of an improvement on higher doses of steroids, although quality of life is better if the hydrocortisone dose is split up, with the highest dose taken in the morning. Thus the evidence suggests that most patients may safely be treated with a low dose of glucocorticoid (e.g. 15 mg hydrocortisone daily) in two or three divided doses, with education about the appropriate action to take in the event of intercurrent illnesses.

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“…Therefore, after GH supplementation, if AI symptoms are observed, increasing the dose of Cortril® should be considered [21,22].…”

Section: I-26mentioning

confidence: 99%

Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline [Opinion]

et al. 2016

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Abstract. This clinical practice guideline of the diagnosis and treatment of adrenal insufficiency (AI) including adrenal crisis was produced on behalf of the Japan Endocrine Society. This evidence-based guideline was developed by a committee including all authors, and was reviewed by a subcommittee of the Japan Endocrine Society. The Japanese version has already been published, and the essential points have been summarized in this English language version. We recommend diagnostic tests, including measurement of basal cortisol and ACTH levels in combination with a rapid ACTH (250 µg corticotropin) test, the CRH test, and for particular situations the insulin tolerance test. Cut-off values in basal and peak cortisol levels after the rapid ACTH or CRH tests are proposed based on the assumption that a peak cortisol level ≥18 µg/ dL in the insulin tolerance test indicates normal adrenal function. In adult AI patients, 15-25 mg hydrocortisone (HC) in 2-3 daily doses, depending on adrenal reserve and body weight, is a basic replacement regime for AI. In special situations such as sickness, operations, pregnancy and drug interactions, cautious HC dosing or the correct choice of glucocorticoids is necessary. From long-term treatment, optimal diurnal rhythm and concentration of serum cortisol are important for the prevention of cardiovascular disease and osteoporosis. In maintenance therapy during the growth period of patients with 21-hydroxylase deficiency, proper doses of HC should be used, and long-acting glucocorticoids should not be used. Education and carrying an emergency card are essential for the prevention and rapid treatment of adrenal crisis.Key words: Adrenal insufficiency, Adrenal crisis, Cortisol, Hydrocortisone, Congenital adrenal hyperplasia Summary of Recommendations I. Chronic adrenal insufficiency (AI) I-1.0 SymptomsWe recommend suspecting AI in patients who have the following symptoms.

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The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults

Cited by 119 publications

References 32 publications

Increased glucocorticoid activation during mouse skin wound healing

Increased glucocorticoid activation during mouse skin wound healing

Why is the management of glucocorticoid deficiency still controversial: a review of the literature

Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline [Opinion]

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