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Effect of Octreotide, a Somatostatin Analog, on Sleep Apnea in Patients with Acromegaly

Ronald R. Grunstein, MBBS; Ken K. Y. Ho, MD; and Colin E. Sullivan, MBBS, PhD
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From the University of Sydney; the Garvan Institute of Medical Research, Saint Vincent's Hospital, Sydney, Australia. Requests for Reprints: Ronald R. Grunstein, MBBS, Sleep Disorders Centre, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, New South Wales 2050, Australia. Acknowledgments: The authors thank Ms. Belinda Brooks, Marijke Phillips, Madeline Kinloch, Christine Johnson, and Deirdre Stewart and the staff of the Sleep Disorders Centre at Royal Prince Alfred Hospital for their expert assistance; Dr. M. Berthon-Jones for statistical and database advice; the physicians of the Departments of Endocrinology at the Westmead Hospital, Prince of Wales, Royal Prince Alfred, and Saint Vincent's hospitals for allowing the authors to study their patients; and Dr. Alan Harris (formerly of Sandoz, Basel) for his interest and encouragement during the planning of this study. Grant Support: In part by the National Health and Medical Research Council of Australia and by a grant from Sandoz Pharma, Basel, Switzerland. Sandoz was not involved in the data collection, analysis, or approval of the final publication of the manuscript.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;121(7):478-483. doi:10.7326/0003-4819-121-7-199410010-00002
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Objective: To determine the effects of octreotide, a somatostatin analog, on the severity of sleep apnea and on growth hormone levels in patients with acromegaly.

Design: Open-label, prospective study.

Setting: Tertiary referral hospital.

Patients: 19 patients with active acromegaly.

Intervention: Octreotide in a 6-month, stepwise incremental dosage.

Measurements: Sleep studies and indices of hormonal activity (levels of insulin-like growth factor 1 [IGF-1] and growth hormone).

Results: A 50% decrease occurred in the respiratory disturbance index (baseline compared with 6 months, 39 events/h compared with 19 events/h; P = 0.0002), and a 40% decrease occurred in total apnea time (27.6% of total sleep time compared with 15.1%; P = 0.001). Indices of oxygen desaturation, sleep quality, and subjective sleepiness improved after 6 months of octreotide. A parallel decrease was noted in mean levels of growth hormone (40.0 µg/L compared with 9.1 µg/L; P = 0.003) and IGF-1 (107 nmol/L compared with 47 nmol/L; P = 0.0001). However, no correlation was noted between the decrease in the total amount of sleep time spent in apnea and the decrease in growth hormone levels (rho = −0.35; P > 0.2). The residual respiratory disturbance index after 6 months of treatment was similar in patients who improved, regardless of whether or not biochemical remission (IGF-1 < 35 nmol/L) occurred.

Conclusions: Improvement in indices of sleep apnea severity occurs in association with octreotide treatment in patients with sleep apnea and acromegaly. However, sleep apnea may either persist despite normalization of growth hormone levels or may improve markedly even if there is only partial biochemical remission.

Figures

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Figure 1.
Respiratory disturbance index in patients with acromegaly and sleep apnea before and during octreotide treatment.nnn

A decrease in the respiratory disturbance index (RDI) was observed in 13 of 14 patients with severe sleep apnea (RDI > 30 apneas/h). Data were measured at baseline ( = 19) and after 3 months ( = 8) and 6 months ( = 19) of octreotide therapy.

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Figure 2.
Obstructive apnea time expressed as percentage of total sleep time in patients with acromegaly and sleep apnea before and during octreotide treatment.nnn

Data were measured at baseline ( = 19) and after 3 months ( = 8) and 6 months ( = 19) of octreotide therapy.

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Figure 3.
Central apnea time expressed as a percentage of total sleep time in patients with acromegaly and sleep apnea before and during octreotide treatment.nnn

Five patients had no central sleep apnea recorded at either baseline or after 6 months of octreotide therapy. Data were measured at baseline ( = 19) and after 3 months ( = 8) and 6 months ( = 19) of octreotide therapy.

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Figure 4.
Insulin-like growth factor 1 concentration and respiratory disturbance index in patients with and without biochemical remission of acromegaly after 6 months of octreotide treatment.open bars

Biochemical remission is defined as IGF-1 levels less than 35 nmol/L. There were 8 patients with remission and 11 patients without remission. Data are expressed as mean ±SE for baseline ( ) and after 6 months (solid bars) of octreotide therapy.

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