Changes in glucose tolerance and development of gall stones during high dose treatment with octreotide for acromegaly.

McKnight, John; McCance, David R.; Crothers, JC; Atkinson, A. B.

doi:10.1136/bmj.299.6699.604

Cited by 49 publications

(13 citation statements)

References 4 publications

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“…This, in turn, is likely to be due to withdrawal of the inhibitory effect of OT on insulin secretion, which is not influenced by pegvisomant. Somatostatin and its analogues decrease insulin release both in normal individuals (32,33) and in patients with GH excess (13,33,34). Further, a recent randomised study comparing the effects of OT and pegvisomant on the insulinogenic response to a standard meal documented inhibition of insulin release by OT with consequent postprandial hyperglycaemia (35).…”

Section: Discussionmentioning

confidence: 99%

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant

Drake

Rowles

Roberts

et al. 2003

European Journal of Endocrinology

119

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Aim and method: Insulin resistance leading, in some cases, to glucose intolerance is an important contributory factor to the cardiovascular morbidity and mortality associated with acromegaly. The aim of this study was to document changes in insulin sensitivity (IS) in a group of seven patients with acromegaly (three male, four female, mean^S.D. age 59^13 years) treated initially with a stable dose of depot octreotide (OT; median dose 30 mg four times weekly, range 10-30 mg) for a median of 18 months (range 16 -19 months) and who were then transferred to treatment with pegvisomant (median dose 15 mg daily, range 10-20 mg) for a median of 8 months (range 7 -9 months). IS was assessed by homeostatic model assessment (HOMA) using fasting glucose and insulin concentrations and by a short insulin tolerance test (sITT). Body composition was assessed by dual energy X-ray absorptiometry. Results: Mean^S.D. serum IGF-I concentrations during therapy with OT and with pegvisomant were not statistically different (283^119 ng/ml on OT vs 191^39 ng/ml on pegvisomant (P ¼ 0.4)). However, mean^S.D. fasting plasma glucose fell from 6.2^1.0 mmol/l on OT to 5.2^0.6 mmol/l on pegvisomant (P ¼ 0.017) and was lower on pegvisomant in all seven patients. In four patients, fasting plasma glucose fell from values diagnostic of diabetes mellitus or impaired fasting glucose on OT to within the normal range on pegvisomant. Mean^S.D. peripheral IS (by sITT) increased from 139^39 mmol/l per min on OT to 169^59 mmol/l per min on pegvisomant (P ¼ 0.037). Mean^S.D. IS (by HOMA %S) was unchanged over the course of the study (149.1^43.7% on OT vs 139.9^76.6% on pegvisomant, P ¼ 0.28). Mean^S.D. pancreatic b-cell secretory function (HOMA %B) improved significantly on pegvisomant compared with OT (49.4^19.2% vs 82.4^43.5%, P ¼ 0.01). No statistically significant change in total fat (P ¼ 0.3), % fat (P ¼ 0.28) or circulating non-esterified fatty acids (P ¼ 0.35) was observed. Conclusions: IS and glucose tolerance improved in patients converted from OT therapy to pegvisomant, without a change in body composition and even when serum IGF-I concentrations remained equally well controlled. This may be an important factor in the choice of medical therapy for patients with acromegaly.

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Section: Discussionmentioning

confidence: 99%

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant

Drake

Rowles

Roberts

et al. 2003

European Journal of Endocrinology

119

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“…Patients felt improved on therapy, but our finding of asymptomatic changes of glucose tol erance and development of gallstones is a cause for con cern [11]. One previous study reported no apparent sideeffects of 1,000 pg 3 times daily [12].…”

Section: Discussionmentioning

confidence: 87%

Somatostatin Analogue (SMS 201-995) in Resistant Acromegaly: A Preliminary Report

Atkinson¹,

McKnight²,

McCance³

et al. 1990

Horm Res

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The results of treating 10 acromegalic patients with octreotide are compared with those of bromocriptine. Bromocriptine (5 mg 4 times daily for 5 weeks) reduced mean growth hormone (GH) concentrations from 60 to 35 mU/1 in 8 patients; a further 2 patients were unable to tolerate this dose. Ten patients (8 unresponsive to bromocriptine) received octreotide 100 µg 3 times daily, rising to 500 µg 3 times daily according to monthly 24-hour GH profiles. Two patients were withdrawn from octreotide therapy; in the remaining 8, mean GH fell from 36 to 11 mU/1 after 6 months’ therapy (a reduction to 22% of basal concentrations, compared to a reduction to 58% on bromocriptine). Asymptomatic changes of glucose tolerance and the development of gallstones were noted; further information on the latter is urgently required. In summary, the smallest effective dose of octreotide should be used and each patient should be monitored biochemically.action than the native hormone [9]. We have studied the effects of octreotide in a group of treatment-resistant acromegalic subjects. GH was assessed by 24-hour profiles, and side effects of octreotide were also investigated. For comparison, the results of a previously published trial [ 10] from our group, which studied the effect of bromocriptine in a similar group of patients, are presented.

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“…We have reported previously variable changes in glucose tolerance during high-dose octreotide (16). In a recent study Ho et al (17) noted normalization of glucose tolerance in four of five patients, with no suppression of serum insulin concentration and an increased ability of insulin to suppress hepatic glucose production.…”

Section: Discussionmentioning

confidence: 94%

“…These were performed annually after the first year. Octreotide was injected subcutaneously at 08.00, 16.00 and 24.00 h. The maximum dose used was 500 µg three times daily.…”

Section: Methodsmentioning

confidence: 99%

Four years' treatment of resistant acromegaly with octreotide

Ja¹,

Dr²,

Sheridan

et al. 1995

European Journal of Endocrinology

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This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21-62 years) with persistent growth hormone (GH) elevation (duration 1-15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 micrograms three times daily. The dose then was reduced to 200 micrograms three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0 +/- 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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Changes in glucose tolerance and development of gall stones during high dose treatment with octreotide for acromegaly.

Cited by 49 publications

References 4 publications

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant

Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant

Somatostatin Analogue (SMS 201-995) in Resistant Acromegaly: A Preliminary Report

Four years' treatment of resistant acromegaly with octreotide

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