256 Journal of Clinical Sleep Medicine, Vol.6, No. 3, 2010 O bstructive sleep apnea (OSA) is a sleep related breath- ing disorder associated with increased cardiovascular morbidity. 1 It is characterized by a recurrent occlusion of the upper airways during sleep, resulting in hypoxia and as- phyxia. 1 The relationship between OSA and abnormalities in the growth hormone (GH)-insulin-like growth factor (IGF)- 1 axis is intricate. In states of GH overproduction, such as acromegaly, the increased occurrence of OSA is associated with anatomical narrowing of the pharyngeal lumen 2,3 and craniofacial changes. 4 Reduced activity in the GH-IGF-1 axis is also associated with OSA, particularly in obese individu- als, 5-7 which can be partly restored by treatment of the OSA by continuous positive airway pressure. 6 Furthermore, pulsa- tile GH secretion is impaired in patients with disturbed sleep architecture and decreased slow wave sleep. 8,9 Abnormalities in the upper airway soft tissue anatomy may play a role in the pathogenesis of OSA in obese individuals. 10 Neck circumference (NC) shows a better correlation than BMI with apnea severity, suggesting that fat deposition in the neck may be involved in the pathogenesis of OSA. 10,11 Other causes of increased neck circumference include increased overnight fuid displacement from the legs to the neck during sleep induced by a recumbent position particularly in indi- viduals with a sedentary way of life. 12 On the other hand, recent data suggest that there is a strong link between OSA and abdominal obesity and the clustering of metabolic abnormalities that characterize the metabolic syndrome. 13 Based on the knowledge that OSA is a common Increased Neck Soft Tissue Mass and Worsening of Obstructive Sleep Apnea after Growth Hormone Treatment in Men with Abdominal Obesity Mahssa Karimi, Ph.C. 1 ; Josef Koranyi, M.D., Ph.C. 2 ; Celina Franco, M.D., Ph.D. 2 ; Yüksel Peker, M.D., Ph.D. 1,3 ; Derek N. Eder, Ph.D. 1 ; Jan-Erik Angelhed, M.D., Ph.D. 4 ; Lars Lönn, M.D. 5 ; Ludger Grote, M.D., Ph.D. 1 ; Bengt-Åke Bengtsson, M.D., Ph.D. 2 ; Johan Svensson, M.D., Ph.D. 2 ; Jan Hedner, M.D., Ph.D. 1 ; Gudmundur Johannsson, M.D., Ph.D. 2 1 Sleep Laboratory, Department of Pulmonary Medicine, Sahlgrenska University Hospital, Göteborg, Sweden; 2 Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden; 3 Sleep Medicine Unit, Department of Neurorehabilitation, Skaraborg Hospital, Skövde, Sweden; 4 Center for Clinical Trials, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; 5 Department of Radiology, and Vascular Surgery, Rigshospitalet, Faculty of Health Sciences, Copenhagen, Denmark SCIENTIFIC INVESTIGATIONS Background: Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) ex- cess and severe GH defciency in adults. Adults with abdomi- nal obesity have markedly suppressed GH secretion. Aim: To study the effect of GH treatment on OSA in abdomi- nally obese men with impaired glucose tolerance. Patients and Methods: Forty men with abdominal obesity and glucose intolerance were randomized in a prospective, 12-month double-blind trial to receive either GH or placebo. The treatment groups had similar BMI and waist circumfer- ence. Overnight polysomnography and computed tomography to assess muscle and fat distribution in the neck and abdomen were performed at baseline and after 12 months. Results: GH treatment increased insulin-like growth-factor-1 from (mean [SD]) 168 (72) to 292 (117) μg/L, the apnea-hy- popnea index from (n/h) 31 (20) to 43 (25) and oxygen-desat- uration index from (n/h) 18 (14) to 29 (21) (p = 0.0001, 0.001, 0.002). Neck transverse diameter, circumference and total cross-sectional area (p = 0.007, 0.01, 0.02) increased, while abdominal visceral adipose tissue (p = 0.007) was reduced. No between-group differences in total sleep time, REM sleep, NREM sleep, and time spent in supine position were found. The Epworth sleepiness scale score was unchanged. Conclusions: GH treatment increased the severity of OSA in abdominally obese men. The possible mechanism appears to be refected by the GH-induced increase of measures of neck volume. The present results, to some extent, argue against that low GH/IGF-I activity is a primary cause of OSA in ab- dominally obese men. Keywords: Growth hormone treatment; obstructive sleep ap- nea; abdominal obesity, GH-IGF-1 axis Citation: Karimi M; Koranyi J; Franco C; Peker Y; Eder DN; Angelhed JE; Lönn L; Grote L; Bengtsson BA; Svensson J: Hedner J; Johannsson G. Increased neck soft tissue mass and worsening of obstructive sleep apnea after growth hor- mone treatment in men with abdominal obesity. J Clin Sleep Med 2010;6(3):256-263. BRIEF SUMMARY Current Knowledge/Study Rationale: The present study aimed to investigate the effect of GH treatment on OSA severity, sleep architecture and soft tissue mass and distribution in the neck in men with abdominal obesity and glucose intolerance. Study Impact: This study suggests that obstructive sleep apnoea se- verity is increased with growth hormone treatment. One possible mecha- nism appears to be refected by the GH-induced increase of measures of neck volume. Downloaded from jcsm.aasm.org by 35.173.36.35 on July 22, 2020. For personal use only. No other uses without permission. Copyright 2020 American Academy of Sleep Medicine. All rights reserved.