Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy

Rodriguez-Arnao, J.; Perry, Les; Besser, G. M.; Ross, R. J. M.

doi:10.1111/j.1365-2265.1996.tb02057.x

Cited by 48 publications

(23 citation statements)

References 25 publications

(23 reference statements)

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“…Our results may be explained by the duration of treatment that is much longer than the 6 -8 week treatment previously reported (14,30). It has been argued that changes in cortisol-binding globulin might explain changes in circulating cortisol levels after GH replacement therapy, but results have been inconsistent (31,32).…”

Section: Discussioncontrasting

confidence: 48%

GH effect on enzyme activity of 11βHSD in abdominal obesity is dependent on treatment duration

Sigurjónsdóttir¹,

Korányi²,

Axelson³

et al. 2006

eur j endocrinol

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Objective: In the past years the interaction of GH and 11bhydroxysteroid dehydrogenase (11bHSD) in the pathogenesis of central obesity has been suggested. Design: We studied the effects of 9 months of GH treatment on 11bHSD activity and its relationship with body composition and insulin sensitivity in 30 men with abdominal obesity, aged 48-66 years, in a randomised, double-blind, placebo-controlled trial. Methods: Urinary steroid profile was used to estimate 11bHSD type 1 and 2 (11bHSD1 and 11bHSD2) activities. Abdominal s.c. and visceral adipose tissues were measured using computed tomography. Glucose disposal rate (GDR) obtained during a euglycaemic -hyperinsulinaemic glucose clamp was used to assess insulin sensitivity. Results: In the GH-treated group the 11bHSD1 activity decreased transiently after 6 weeks (P , 0.01) whereas 11bHSD2 increased after 9 months of treatment (P , 0.05). Between 6 weeks and 9 months, GDR increased and visceral fat mass decreased. Changes in 11bHSD1 correlated with changes in visceral fat mass between baseline and 6 weeks. There were no significant correlations between 11bHSD1 and 11bHSD 2 and changes in GDR. Discussion: The study demonstrates that short-and long-term GH treatment has different effects on 11bHSD1 and 11bHSD2 activity. Moreover, the data do not support that long-term metabolic effects of GH are mediated through its action on 11bHSD.European Journal of Endocrinology 154 69-74

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Section: Discussioncontrasting

confidence: 48%

GH effect on enzyme activity of 11βHSD in abdominal obesity is dependent on treatment duration

Sigurjónsdóttir¹,

Korányi²,

Axelson³

et al. 2006

eur j endocrinol

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“…In 1994, Weaver et al raised the possibility that this could be a mineralocorticoid effect, but their findings did not support this hypothesis [7]. Instead, they demonstrated that GH replacement was associated with a decrease in cortisol metabolites, a possible reduction in GC sensitivity and a decrease in CBG levels, findings that were also reported by others in 1996 [7, 52]. Subsequently, it was concluded that GH therapy in hypopituitary adults is associated with an apparent reduction in the availability of administered HC as measured by urine cortisol metabolites and urine free cortisol, suggesting that GH may directly or indirectly modulate the activity of 11-β-HSD type 1 [7, 53, 54].…”

Section: Gc Replacement In Hypopituitarismsupporting

confidence: 50%

Management of Glucocorticoid Replacement in Adult Growth Hormone Deficiency

Filipsson¹,

Johannsson²

2007

Horm Res Paediatr

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In multiple pituitary hormone deficiency, interactions occur among thyroxine, cortisol and growth hormone (GH). This review addresses the issues of endogenous cortisol production and exogenous cortisol replacement and discusses cortisol metabolism in the context of adult GH deficiency. In addition, we review the effect of GH on 11-β-hydroxysteroid dehydrogenase type 1, the current literature regarding the choice of glucocorticoid (GC) treatment and dose levels and dosing regimens. Recommendations for GC replacement therapy are also provided.

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“…The GH-IGF1 axis may inhibit 11bHSD type 1 expression (84). GH therapy in patients with hypopituitarism on stable HC therapy reduces the mean cortisol peak and total cortisol exposure (85). GH therapy reduces the mean ratio of Fm/Em (ratio of urine cortisol to cortisone metabolites) bringing patients with hypopituitarism on HC treatment closer to physiological glucocorticoid exposure.…”

Section: Hormonal and Drug Interactionsmentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

114

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Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but many suffer from poor quality of life, and overall there is increased mortality. Moreover, it appears that use of glucocorticoids at the higher end of the replacement dose range is associated with increased risk for cardiovascular and metabolic bone disease. These data highlight some of the inadequacies of current regimes.The cortisol production rate is estimated to be equivalent to 5.7-7.4 mg/m 2 per day, and a major difficulty for replacement regimes is the inability to match the distinct circadian rhythm of circulating cortisol levels, which are low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after waking and then fall during the day. Another issue is that current dose equivalents of glucocorticoids used for replacement are based on anti-inflammatory potency, and few data exist as to doses needed for equivalent cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most refined regime for current oral therapy, but does not replicate the normal cortisol rhythm. Recently, proof-of-concept studies have shown that more physiological circadian glucocorticoid therapy using HC infusions and newly developed oral formulations of HC have the potential for better biochemical control in patients with adrenal insufficiency. Whether such physiological replacement will have an impact on the complications seen in patients with adrenal insufficiency will need to be analysed in future clinical trials.

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Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy

Cited by 48 publications

References 25 publications

GH effect on enzyme activity of 11βHSD in abdominal obesity is dependent on treatment duration

GH effect on enzyme activity of 11βHSD in abdominal obesity is dependent on treatment duration

Management of Glucocorticoid Replacement in Adult Growth Hormone Deficiency

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

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