Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study

Dal, Jakob; Klose, Marianne; Heck, Ansgar; Andersen, Marianne; Kistorp, Caroline; Bollerslev, Jens; Feldt‐Rasmussen, Ulla; Jørgensen, Jens Otto Lunde

doi:10.1530/eje-17-0546

Cited by 19 publications

(19 citation statements)

References 27 publications

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“…On the contrary, uncontrolled GH or IGF-1 resulted in a significant increase of the SMR of 1.96 (CI: 1.25-3.05, I2: 78%) as compared with the general population, according to this meta-analysis. Once medically treated, it remains unknown if targeting GH or IGF-1 instead of both parameters in patients with acromegaly could be a suitable strategy, however this question has been recently raised by the group of Dal et al [34]. While somatostatin analogs have been associated either with a higher risk of GH discordance (i.e., IGF-1 normal with unsuppressed GH under OGTT) [22,34,35] or a higher proportion of IGF-1 discordance [21], this study shows that increasing the dose of somatostatin analogs based on either GH or IGF-1, significantly increased the proportion of controlled patients after a follow-up of 12 months.…”

Section: Endocrinementioning

confidence: 99%

Discordant biological parameters of remission in acromegaly do not increase the risk of hypertension or diabetes: a study with the Liege Acromegaly Survey database

et al. 2020

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Purpose Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease; however, a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of diabetes mellitus (DM) and hypertension (HT) in acromegalic patients with congruent GH and/or IGF-1 levels vs. discordant biochemical parameters. Methods Retrospective analysis of the data of 3173 patients from the Liege Acromegaly Survey (LAS) allowed us to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning DM and HT both at diagnosis and at the last follow-up (LFU). We recorded the number of anti-HT and anti-DM drugs used at the first evaluation and at LFU for every patient. Results Ninety-nine patients belonged to the REM group (concordant parameters), 65 patients were considered as GH dis (high random GH/controlled IGF-1), and 26 patients were considered as IGF-1 dis (high IGF-1/controlled random GH). At diagnosis, 72 patients (37.8%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of the number of anti-HT and anti-DM drugs at diagnosis versus LFU (mean duration: 7.3 ± 4.5 years) between all three groups. Conclusion The long-term outcome of DM and HT in acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.

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Section: Endocrinementioning

confidence: 99%

Discordant biological parameters of remission in acromegaly do not increase the risk of hypertension or diabetes: a study with the Liege Acromegaly Survey database

et al. 2020

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“…The authors reported significantly higher GH nadir levels along with worse symptoms and quality of life in controlled patients treated with somatostatin analogues compared to surgery despite comparable IGF-I and fasting GH levels [109]. Dose escalation of somatostatin analogues minimized the discordance between IGF-1 and nadir GH levels with, however, no improvement in quality of life [108]. Furthermore, higher GH nadir levels after an OGTT as well as after mixed meals were observed in patients treated with somatostatin analogues compared to patients successfully treated with surgery and matched to IGF-1 levels suggesting a residual disease activity in somatostatin analogue treated patients despite normalized IGF-I levels [107].…”

Section: Ogtt In the Follow-up Of Acromegalymentioning

confidence: 99%

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

Hage

Kamenický

Chanson³

2019

Neuroendocrinology

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The exact physiological basis of acute growth hormone (GH) suppression by oral glucose is not fully understood. Glucose-mediated increase in hypothalamic somatostatin seems to be the most plausible explanation. Attempts to better understand its underlying mechanisms are compromised by species disparities in the response of GH to glucose load. While in humans, glucose inhibits GH release, the acute elevation of circulating glucose levels in rats has either no effect on GH secretion or may be stimulatory. Likewise, chronic hyperglycemia alters GH release in both humans and rats nonetheless in opposite directions. Several factors influence nadir GH concentrations including, age, gender, body mass index, pubertal age, and the type of assay used. Besides the classical suppressive effects of glucose on GH release, a paradoxical GH increase to oral glucose may be observed in around one third of patients with acromegaly as well as in various other disorders. Though its pathophysiology is poorly characterized, an altered interplay between somatostatin and GH-releasing hormone has been suggested and a link with pituitary ectopic expression of glucose-dependent insulinotropic polypeptide receptor has been recently demonstrated. A better understanding of the dynamics mediating GH response to glucose may allow a more optimal use of the OGTT as a diagnostic tool in various conditions, especially acromegaly.

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“…Furthermore, discrepant results from GH nadir and IGF-I analysis can also delay diagnosis, and apart from assay problems, biological variables might be important (8). Sex, BMI and different cycle phase have been shown to influence the GH nadir , but few studies systematically addressed this, and there is no consensus if and how cut-offs should be adjusted to such variables (9,21,22,23,24,25,26,27).…”

Section: Introductionmentioning

confidence: 99%

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

Schilbach

Gar

Lechner

et al. 2019

European Journal of Endocrinology

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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.

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Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study

Cited by 19 publications

References 27 publications

Discordant biological parameters of remission in acromegaly do not increase the risk of hypertension or diabetes: a study with the Liege Acromegaly Survey database

Discordant biological parameters of remission in acromegaly do not increase the risk of hypertension or diabetes: a study with the Liege Acromegaly Survey database

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

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

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