The International Journal of Romanian Society of Endocrinology / Registered in 1938

in Web of Science Master Journal List

Acta Endocrinologica(Bucharest) is live in PubMed Central

Journal Impact Factor - click here.

January - March 2005, Volume 1, Issue 1
Endocrine Care

Niculescu DA, Botusan I, Rasanu C, Radian S, Filip O, Coculescu M

Central sleep apnea in acromegaly versus obesity

Acta Endo (Buc) 2005, 1 (1): 79-88
doi: 10.4183/aeb.2005.79

INTRODUCTION: Sleep apnea syndrome is a common manifestation of acromegaly. Although the obstructive type of apnea was thought to be predominant there are some reports suggesting that central apneic episodes show a high rate and are related to abnormalities of central respiratory control.\r\nAIM: The present study determines the presence and severity of central sleep apnea syndrome in patients with acromegaly compared with obese subjects.\r\nMATERIALS AND METHODS: 35 consecutive acromegalic patients (min GH (growth hormone) during oral glucose tolerance test (OGTT) 6.6 ng/ml) and 19 obese subjects (BMI=44 kg/m2) were polisomnographically recorded between 10 p.m and 6 a.m. Sleep and respiratory disturbances were manually staged according to standard criteria.\r\nRESULTS: The prevalence of sleep apnea syndrome in acromegaly group was 45.7% (16 out of 35 patients). The median of minimum GH level during OGTT was 8.3 ng/ml in apnea group and 5.16 ng/ml in nonapneic group (p>0.05). In acromegaly group with severe sleep apnea syndrome central apnea rate was greater than 10% in 6 out of 7 subjects with REM sleep and in 7 out of 10 with NREM sleep whereas in obesity group this percent was present in 6 out of 18 (REM sleep), respectively 7 out of 19 (NREM sleep).\r\nCONCLUSIONS: The study confirms the high prevalence of sleep apnea in acromegaly. GH serum level is not an indicator for the presence and severity of sleep apnea. Although the total time of central apnea per hour of sleep did not differ between the two groups, the percent (rate) of central apnea was significantly greater in acromegaly group.

Keywords: acromegaly, obesity, sleep, apnea, respiration

Correspondence: Dan Niculescu, MD, Endocrinology Department, ?Carol Davila? University of Medicine and Pharmacy, 36 Bdul Aviatorilor, 011863, Bucharest, Romania, e-mail:


1. Laroche C, Festal G, Poenaru S, Caquet R, Lemaigre D, Auperin A. [A case of periodic respiration in a patient with acromegaly]. Ann Med Interne (Paris) 1976; 127(5):381-385.
2. Roxburgh F, Collis A. Notes on a case of acromegaly. Br Med J 1886; 2:63-65.
3. Grunstein RR, Ho KY, Sullivan CE. Sleep apnea in acromegaly. Ann Intern Med 1991; 115(7): 527-532.
4. Pelttari L, Polo O, Rauhala E, Vuoriluoto J, Aitasalo K, Hyyppa MT et al. Nocturnal breathing abnormalities in acromegaly after adenomectomy. Clin Endocrinol (Oxf) 1995; 43(2):175-182. [CrossRef]
5. Rosenow F, Reuter S, Deuss U, Szelies B, Hilgers RD, Winkelmann W et al. Sleep apnoea in treated acromegaly: relative frequency and predisposing factors. Clin Endocrinol (Oxf) 1996; 45(5):563-569. [CrossRef]
6. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004; 25(1):102-152. [CrossRef]
7. Grunstein RR, Ho KY, Berthon-Jones M, Stewart D, Sullivan CE. Central sleep apnea is associated with increased ventilatory response to carbon dioxide and hypersecretion of growth hormone in patients with acromegaly. Am J Respir Crit Care Med 1994; 150(2
8. Rechtschaffen A, Kales A. A Manual of Standardized Terminology, Techniques, and Scoring System for Sleep Stages of Human Subjects. Washington, DC: National Institutes of Health, 1968.
9. American Academy of Sleep Medicine. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22(5):6
10. Kryger M. Monitoring Respiratory and Cardiac Function. In: Kryger M, Roth T, Dement W, editors. Principles and Practice of Sleep Medicine. Philadelphia: W.B. Saunders, 2000: 1217-1230.
11. Dostalova S, Sonka K, Smahel Z, Weiss V, Marek J, Horinek D. Craniofacial abnormalities and their relevance for sleep apnoea syndrome aetiopathogenesis in acromegaly. Eur J Endocrinol 2001; 144(5):491-497. [CrossRef]
12. Hochban W, Brandenburg U. Morphology of the viscerocranium in obstructive sleep apnoea syndrome?cephalometric evaluation of 400 patients. J Craniomaxillofac Surg 1994; 22(4):205-213. [CrossRef]
13. Hochban W, Ehlenz K, Conradt R, Brandenburg U. Obstructive sleep apnoea in acromegaly: the role of craniofacial changes. Eur Respir J 1999; 14(1):196-202. [CrossRef]
14. Herrmann BL, Wessendorf TE, Ajaj W, Kahlke S, Teschler H, Mann K. Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly. Eur J Endocrinol 2004; 151(3):309-315. [CrossRef]
15. Isono S, Saeki N, Tanaka A, Nishino T. Collapsibility of passive pharynx in patients with acromegaly. Am J Respir Crit Care Med 1999; 160(1):64-68.
16. Weiss V, Sonka K, Pretl M, Dostalova S, Klozar J, Rambousek P et al. Prevalence of the sleep apnea syndrome in acromegaly population. J Endocrinol Invest 2000; 23(8):515-519.
17. Cadieux RJ, Kales A, Santen RJ, Bixler EO, Gordon R. Endoscopic findings in sleep apnea associated with acromegaly. J Clin Endocrinol Metab 1982; 55(1):18-22. [CrossRef]
18. Lindgren AC, Hellstrom LG, Ritzen EM, Milerad J. Growth hormone treatment increases CO(2) response, ventilation and central inspiratory drive in children with Prader-Willi syndrome. Eur J Pediatr 1999; 158(11):936-940. [CrossRef]
19. Grunstein RR, Ho KY, Berthon-Jones M, Stewart D, Sullivan CE. Central sleep apnea is associated with increased ventilatory response to carbon dioxide and hypersecretion of growth hormone in patients with acromegaly. Am J Respir Crit Care Med 1994; 150(2
20. Llona I, Ampuero E, Eugenin JL. Somatostatin inhibition of fictive respiration is modulated by pH. Brain Res 2004; 1026(1):136-142. [CrossRef]
21. Chen ZB, Engberg G, Hedner T, Hedner J. Antagonistic effects of somatostatin and substance P on respiratory regulation in the rat ventrolateral medulla oblongata. Brain Res 1991; 556(1):13-21. [CrossRef]
22. Pedersen ME, Dorrington KL, Robbins PA. Effects of somatostatin on the control of breathing in humans. J Physiol 1999; 521 Pt 1:289-297. [CrossRef]
23. Lopata M, Freilich RA, Onal E, Pearle J, Lourenco RV. Ventilatory control and the obesity hypoventilation syndrome. Am Rev Respir Dis 1979; 119(2 Pt 2):165-168.
24. Zwillich CW, Sutton FD, Pierson DJ, Greagh EM, Weil JV. Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome. Am J Med 1975; 59(3):343-348. [CrossRef]
25. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334(5):292-295. [CrossRef]
26. Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte D, Jr. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med 1996; 2(5):589-593. [CrossRef]
27. Fruhbeck G, Jebb SA, Prentice AM. Leptin: physiology and pathophysiology. Clin Physiol 1998; 18(5):399-419. [CrossRef]
28. Lundberg JM, Pernow J, Fried G, Anggard A. Neuropeptide Y and noradrenaline mechanisms in relation to reserpine induced impairment of sympathetic neurotransmission in the cat spleen. Acta Physiol Scand 1987; 131(1):1-10. [CrossRef]
29. Mann K, Benkert O, R?schke J. Effects of corticotropin-releasing hormone on respiratory parameters during sleep in normal men. Exp Clin Endocrinol 1994; 103:233-240. [CrossRef]
30. O?donnell CP, Schaub CD, Haines AS, Berkowitz DE, Tankersley CG, Schwartz AR et al. Leptin prevents respiratory depression in obesity. Am J Respir Crit Care Med 1999; 159(5 Pt 1):1477-1484.
31. Shimura R, Tatsumi K, Nakamura A, Kasahara Y, Tanabe N, Takiguchi Y et al. Fat accumulation, leptin, and hypercapnia in obstructive sleep apnea-hypopnea syndrome. Chest 2005; 127(2):543-549. [CrossRef]
32. Tatemoto K. Neuropeptide Y: complete amino acid sequence of the brain peptide. Proc Natl Acad Sci USA 1982; 79(18):5485-5489. [CrossRef]
33. Clark JT, Karla PS, Crowley WR, Karla SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology 1984; 115:427-429. [CrossRef]
34. Stanley BG, Kyrkouli SE, Lampert S, Leibowitz SF. Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 1986; 7(6):1189-1192. [CrossRef]
35. Thorsell A, Heilig M. Diverse functions of neuropeptide Y revealed using genetically modified animals. Neuropeptides 2002; 36(2-3):182-193. [CrossRef]
36. Nam SY, Kratzsch J, Kim KW, Kim KR, Lim SK, Marcus C. Cerebrospinal fluid and plasma concentrations of leptin, NPY, and alpha-MSH in obese women and their relationship to negative energy balance. J Clin Endocrinol Metab 2001; 86(10):4849-4853. [CrossRef]
37. Harfstrand A. Brain neuropeptide Y mechanisms. Basic aspects and involvement in cardiovascular and neuroendocrine regulation. Acta Physiol Scand Suppl 1987; 565:1-83.
38. Morton KD, McCloskey MJ, Potter EK. Cardiorespiratory responses to intracerebroventricular injection of neuropeptide Y in anaesthetised dogs. Regul Pept 1999; 81(1-3):81-88. [CrossRef]