Treatment-related changes in sleep apnea syndrome in patients with acromegaly: a prospective study Thalijn Wolters 1 *, Sean Roerink 1 *, Linda Drenthen 1, Jolanda van Haren- Willems 2, Guido van den Broek 3, Kim Rutten 4, Jan Smit 1, Ad Hermus 1 & Romana Netea-Maier 1 Radboud University Medical Center; Departments of 1 Internal Medicine, 2 Pulmonary Diseases, Otolaryngology/Head & Neck Surgery and 4 Rehabilitation; Nijmegen, the Netherlands Abstract SAT 467-30962 ENDO 2017; Orlando
Sleep apnea syndrome (SAS) Prevalence in acromegaly: 20-80% 1,2 Obstructive SAS (OSAS) most common 1,3 1 Colao et al., Endocr Rev, 2004 2 Attal & Chanson, J Clin Endocrinol Metab 2010 3 Castellani et al., Endocrine 2016
Clinical relevance (O)SAS is linked to all-cause mortality 1 cardiovascular disease (CVD) 1 1 Selim, Won & Yaggi. Clin Chest Med. 2010 2 Meslier et al Eur Respir J. 2003 3 Rodenstein. Respiration. 2009 4 Engleman & Douglas. Thorax. 2004 impaired glucose tolerance & diabetes mellitus type 2 2 concentration problems, traffic & occupational accidents 3 sleepiness & impaired Quality of Life 4 Aim To prospectively analyse sleep parameters in acromegaly patients during the first 2,5 years of treatment Pagina 3
Methods Baseline Start SSA 6 months EETA 1 year 1,5 years 2 years 2,5 years T 0 - PSG, ESS,IGF-1 T 1 - PSG, ESS, IGF-1 T 2 - PSG, ESS, IGF-1 PSG: Polysomnography; ESS: Epworth Sleepiness Scale; EETA: Endoscopic Endonasal Transsphenoidal Adenectomy; SSA: Somatostatin Analogue. Pagina 4
Polysomnography (PSG) parameters Apnea + hypopnea + RERA = Respiratory disturbance index (RDI) Oxygen desaturation index (ODI) Lowest O 2 saturation (SaO 2 ) SAS: RDI 5 and symptoms or increased ESS score 1,2 Mild: 5 RDI <15 Moderate: 15 RDI <30 Severe: RDI 30 1 Epstein, L.J., et al., J Clin Sleep Med, 2009. 2 Iber et al, The AASM Manual for the Scoring of Sleep and Associated Events. 2007. Pagina 5
Patient characteristics Baseline All patients (n=15) Sex: male/female; n (%) 7 (46.7%) / 8 (53.3%) Age (years) 54.87 (3.5) Length (m) 1.76 (0.04) Weight (kg) 87.2 (3.9) BMI (kg/m 2 ) 28.12 (0.8) Hypertension / Diabetes mellitus / Dyslipidemia 6 (40%) / 3 (20%) / 4 (26.7%) GH (me/l) 23.05 (6 97.9) IGF-1 (nmol/l) 96.45 (9.9) Systolic RR (mmhg) 128 (110-190) Diastolic RR (mmhg) 80.47 (2.5) Current smoker 1 (6.7%) Alcohol consumption (yes/no) 11 (73.3%) Hypothyroidism / Hypocortisolism / Hypogonadism 1(6.7%) / 1 (6.7%) / 9 (60%) Values are presented as mean (SEM) or median (minimum-maximum), depending on the normality of the distribution Pagina 6
IGF-1 levels during follow-up T 0 T 1 T 2 P T 0 vs. T 1 P T 0 vs. T 2 82.95 (40.6-208) 24.1 (8.5-36.5) 26.73 (10.2-34.1) <0.001 0.009 Pagina 7
RDI during follow-up SAS 93.3% 50% 13.3% T 0 T 1 T 2 No OSAS 1 (6.7%) 7 (50%) 13 (86.7%) Mild OSAS 5 (33.3%) 4 (28,6%) 1 (6.7%) Moderate OSAS 3 (20%) 1 (7,1%) 1 (6,7% ) Severe OSAS 6 (40%) 2 (14,3%) 0 (0%) T 0 : OSAS 66,7%; Mixed 6,7%; Hypopnea 26,7% T 0 T 1 T 2 P T 0 vs. T 1 P T 0 vs. T 2 27.4 (3.1-99.2) 8.85 (1.9-95) 6.55 (0.4-24.1) 0.03 0.002 Pagina 8
Correlation RDI & IGF-1 levels R = 0,998
Lowest SaO 2 during follow-up T 0 T 1 T 2 P T 0 vs. T 1 P T 0 vs. T 2 81.1 (2) 82.1 (2.4) 87.0 (0.8) 0.13 0.001 Pagina 10
Correlation lowest SaO 2 & IGF-1 levels R = 1,0
ESS scores during follow-up T 0 T 1 T 2 P T 0 vs. T 1 P T 0 vs. T 2 12.07 (1.24) 6.5 (1.24) 6.71 (0.74) 0.002 <0.001 Pagina 12
Correlation ESS scores & IGF-1 levels R = 0,994
ODI during follow-up T 0 T 1 T 2 P T 0 vs. T 1 P T 0 vs. T 2 22.65 (2.8-80.5) 7 (0.8-63.6) 6.44 (0.3-21) 0.01 <0.001 Pagina 14
Correlation ODI & IGF-1 levels R = 1,0
Conclusions High prevalence of OSAS in untreated acromegaly Significant improvement during treatment Strongest improvement in first year of treatment PSG parameters correlate with IGF-1 levels Recommendation: PSG at diagnosis in case of snoring, apneas and/or tiredness No OSAS: PSG when indicated OSAS: repeat PSG during treatment (after 1-2 years) Pagina 16
Acknownledgements Department of Internal Medicine Radboudumc Nijmegen Division of Endocrinology Sean Roerink, MD Margreet Wagenmakers, MD, PhD Romana Netea-Maier, MD, PhD Prof Ad Hermus, MD Prof Jan Smit, MD Linda Drenthen, MD Department of Pulmonary Diseases Jolanda van Haren-Willems, MD, PhD Anja Jacobs-Verhoeven Pagina 17
Treatment-related changes in sleep apnea syndrome in patients with acromegaly: a prospective study Thalijn Wolters 1 *, Sean Roerink 1 *, Linda Drenthen 1, Jolanda van Haren- Willems 2, Jan Smit 1, Ad Hermus 1 & Romana Netea-Maier 1 1 Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen. 2 Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen. Abstract SAT 467-30962 ENDO 2017; Orlando
AHI during follow-up T0 T1 T2 P T0 vs. T1 P T0 vs. T2 19.9 (2.9-64.6) 4.8 (1.1-52.8) 4 (0.4-20.8) 0.02 0.003 Pagina 19
Correlation AHI & IGF-1 levels R=0,999; p = 0,001