Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Neggers, Sebastian J C M M; Kopchick, John J.; Jørgensen, Jens Otto Lunde; Lely, AJ van der

doi:10.1530/eje-10-0969

Cited by 56 publications

(42 citation statements)

References 54 publications

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“…16 This observation may be attributed to a GH-independent suppressive effect of SSAs on hepatic IGF-I production. 26 The present study confirmed a significantly higher frequency of discordant GH and IGF-I values among patients who received SSAs vs non-SSAtreated patients (32Á5% vs 21Á6%). However, regarding the pattern of discordance, the 'High IGF-I' type of discordance was more common among patients under SSA treatment, probably reflecting the fact that SSAs powerfully suppress GH pulses, but have only limited effect on basal GH secretion.…”

Section: Discussionsupporting

confidence: 81%

The ongoing challenge of discrepant growth hormone and insulin‐like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta‐analysis

Kanakis

Chrisoulidou

Bargiota

et al. 2016

Clinical Endocrinology

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SummaryObjective Growth hormone (GH) and insulin-like growth factor I (IGF-I) are the principal biomarkers used to assess disease activity in acromegaly, and any discrepancy between them renders interpretation of results inconclusive. Purpose of this study was to assess the frequency of this discrepancy and identify parameters that might affect its occurrence. Design A systematic review of MEDLINE and Scopus was performed followed by a meta-analysis to address the frequency of discrepant results between GH and IGF-I levels. Meta-regression and subgroup analyses were performed assessing the effects of the year of publication, the different types of GH testing and GH assays used, as well as the impact of treatment with somatostatin analogues (SSAs) on the occurrence of this discrepancy. Results The analysis retrieved 39 eligible studies totalling 7071 patients. The pooled discordance rate between GH and IGF-I was 25Á7% (95% CI: 22Á3-29Á4), and the predominant format was that of elevated IGF-I with normal GH levels (15Á3%, 95% CI: 12Á5-18Á7). No significant correlation between the discordance rate and the year of publication was shown; whereas, the use of ultrasensitive GH assays resulted in higher discordance rates (30Á7%, 95% CI: 25Á9-35Á9 vs 19Á8%, 95% CI: 14Á1-27Á2, P = 0Á04) as did treatment with SSAs (32Á5%, 95% CI: 27Á8-37Á4) vs (21Á6%, 95% CI: 17Á8-25Á6, P = 0Á001).Conclusions Discrepancy between GH and IGF-I results is encountered in a quarter of treated patients with acromegaly, especially when using ultrasensitive GH assays or in patients receiving SSAs, a fact that the clinician should take into consideration when making clinical decisions.

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Section: Discussionsupporting

confidence: 81%

The ongoing challenge of discrepant growth hormone and insulin‐like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta‐analysis

Kanakis

Chrisoulidou

Bargiota

et al. 2016

Clinical Endocrinology

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“…In addition, a new concept of extrahepatic acromegaly induced by SSTA has been introduced. It is postulated by Neggers et al (37) that long-acting SSTA normalize serum IGF1 levels in certain patients in the presence of elevated GH actions in extrahepatic tissues. Also, Rubeck et al (38) compared traditional and novel biomarkers and health status in patients with acromegaly treated with either surgery alone or SSTA.…”

Section: Discussionmentioning

confidence: 99%

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly

Postma

Netea‐Maier²,

Berg³

et al. 2012

European Journal of Endocrinology

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Objective: To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly. Design: This is a cross-sectional study in two tertiary referral centers in The Netherlands. Patients and methods: One hundred and eight patients with acromegaly, in whom transsphenoidal (nZ101, 94%) or transcranial (nZ7, 6%) surgery was performed. Subsequently, 46 (43%) received additional radiotherapy and 41 (38%) were on postoperative treatment with SSTA because of persistent or recurrent disease at the time of study. All subjects filled in standardized questionnaires measuring HR-QoL. Disease control at the time of study was assessed by local IGF1 SDS. Results: IGF1 SDS were slightly higher in patients treated with SSTA in comparison with patients without use of SSTA (0.85G1.52 vs 0.25G1.21, PZ0.026), but the percentage of patients with insufficient control (IGF1 SDS O2) was not different (17 vs 9%, PZ0.208). Patients using SSTA reported poorer scores on most subscales of the RAND-36 and the acromegaly QoL and on all subscales of the multidimensional fatigue inventory-20. A subgroup analysis in patients with similar IGF1 levels (SSTAC, nZ26, IGF1 SDS 0.44G0.72 vs SSTAK, nZ44, IGF1 SDS 0.41G0.65) revealed worse scores on physical functioning, physical fatigue, reduced activity, vitality, and general health perception across all HR-QoL questionnaires in patients treated with SSTA. Conclusion: QoL is impaired in association with the need for prolonged postoperative therapy by SSTA in patients with acromegaly despite similar IGF1 levels.

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“…Neggers et al (39) summarised these observations in their hypothesis of an extra-hepatic acromegaly. SSA decreases not only the GH levels of the pituitary but also reduces the insulin production from the pancreatic b-cells.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

Droste¹,

Domberg²,

Buchfelder

et al. 2014

European Journal of Endocrinology

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Objective: Acromegaly is associated with an increased prevalence of glucose metabolism disorders. Clinically confirmed diabetes mellitus is observed in approximately one quarter of all patients with acromegaly and is known to have a worse prognosis in these patients. Design: Of 514 acromegalic patients treated with pegvisomant and recorded in the German Cohort of ACROSTUDY, 147 had concomitant diabetes mellitus. We analysed these patients in an observational study and compared patients with and without concomitant diabetes. Results: Under treatment with pegvisomant, patients with diabetes mellitus rarely achieved normalisation (64% in the diabetic cohort vs 75% in the non-diabetic cohort, PZ0.04) for IGF1. Diabetic patients normalised for IGF1 required higher pegvisomant doses (18.9 vs 15.5 mg pegvisomant/day, P!0.01). Furthermore, those diabetic patients requiring insulin therapy showed a tendency towards requiring even higher pegvisomant doses to normalise IGF1 values than diabetic patients receiving only oral treatment (22.8 vs 17.2 mg pegvisomant/day, PZ0.11). Conclusions: Hence, notable interdependences between the acromegaly, the glucose metabolism of predisposed patients and their treatment with pegvisomant were observed. Our data support recent findings suggesting that intra-portal insulin levels determine the GH receptor expression in the liver underlined by the fact that patients with concomitant diabetes mellitus, in particular those receiving insulin therapy, require higher pegvisomant doses to normalise IGF1. It is therefore important to analyse various therapy modalities to find out whether they influence the associated diabetes mellitus and/or whether the presence of diabetes mellitus influences the treatment results of an acromegaly therapy.

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Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Cited by 56 publications

References 54 publications

The ongoing challenge of discrepant growth hormone and insulin‐like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta‐analysis

The ongoing challenge of discrepant growth hormone and insulin‐like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta‐analysis

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

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