P-102 The relationship between central adrenal insufficiency and sleep related breathing disorders in children with Prader-Willi syndrome

Background: The annual death rate of patients with Prader-Willi syndrome (PWS) is high (3%). Many deaths of children are sudden and unexplained. Sleep apneas have been suggested to play a role in sudden deaths. Recently, we discovered that 60% of patients with PWS suffer from central adrenal insufficiency (CAI) during stress. Objective: The aim was to study the relationship between CAI and sleep-related breathing disorders. Design: In 20 children with PWS who underwent a metyrapone test (30 mg/kg at 2330 h), sleep-related breathing was evaluated by polysomnography before the metyrapone test. In addition, we recorded sleep-related breathing in 10 children with PWS during their metyrapone test. CAI was diagnosed when ACTH levels during the metyrapone test were below 33 pmol/liter at 0730 h. All tests were performed during healthy condition. Setting: The study was conducted in a pediatric intensive care unit and specialized sleep center. Results: Median (interquartile range) age was 8.4 yr (6.5–10.2). After metyrapone administration, median (interquartile range) central apnea index (number/hour) increased significantly from 2.2 (0.4–4.7) to 5.2 (1.5–7.9) (P = 0.007). The increase tended to be higher in children with CAI [2.8 (2.0–3.9) vs. 1.0 (−0.2 to 2.6); P = 0.09]. During polysomnography before the metyrapone test, sleep-related breathing was worse in children with CAI, who had a significantly higher central apnea index and tended to have a lower minimum oxygen saturation compared to those without CAI (P = 0.03 and P = 0.07). Conclusions: In children with PWS, the central apnea index increased significantly after metyrapone administration, particularly in those with CAI during stress. In addition, children with CAI had a higher central apnea index compared to those without several months before the metyrapone test.

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No central adrenal insufficiency found in adults with prader-willi syndrome tested by multiple dose metyrapone test

Endocrine Abstracts ◽

10.1530/endoabs.63.p235 ◽

2019 ◽

Author(s):

Anna Rosenberg ◽

Karlijn Pellikaan ◽

Kirsten Davidse ◽

Stephany Donze ◽

Anita Hokken-Koelega ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Multiple Dose ◽

Prader Willi Syndrome ◽

Central Adrenal Insufficiency

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Comparison of Frequency and Severity of Sleep-Related Breathing Disorders in Children with Simple Obesity and Paediatric Patients with Prader–Willi Syndrome

Journal of Personalized Medicine ◽

10.3390/jpm11020141 ◽

2021 ◽

Vol 11 (2) ◽

pp. 141

Author(s):

Agnieszka Lecka-Ambroziak ◽

Marta Wysocka-Mincewicz ◽

Anna Świercz ◽

Małgorzata Jędrzejczak ◽

Mieczysław Szalecki

Keyword(s):

Insulin Resistance ◽

Apnea Hypopnea Index ◽

Oral Glucose ◽

Prader Willi Syndrome ◽

Model Assessment ◽

Sleep Related Breathing Disorders ◽

Breathing Disorders ◽

Simple Obesity ◽

Rhgh Treatment ◽

Group 1

Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader–Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients—with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea–hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients’ care.

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SAT-446 No Central Adrenal Insufficiency Found in Adults with Prader-Willi Syndrome Tested by Multiple-Dose Metyrapone Test

Journal of the Endocrine Society ◽

10.1210/js.2019-sat-446 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Kirsten Davidse ◽

Anna Rosenberg ◽

Karlijn Pellikaan ◽

Stephany Donze ◽

Anita Hokken-Koelega ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Multiple Dose ◽

Prader Willi Syndrome ◽

Central Adrenal Insufficiency

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Sleep-Related Breathing Disorders in Young Adults With Prader-Willi Syndrome: A Placebo-Controlled, Crossover GH Trial

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00391 ◽

2019 ◽

Vol 104 (9) ◽

pp. 3931-3938

Author(s):

Stephany H Donze ◽

Al W de Weerd ◽

Renilde A S van den Bossche ◽

Koen F M Joosten ◽

Anita C S Hokken-Koelega

Keyword(s):

Young Adults ◽

Adult Height ◽

Uniparental Disomy ◽

Apnea Hypopnea Index ◽

Prader Willi Syndrome ◽

Double Blind ◽

Sleep Related Breathing Disorders ◽

Maternal Uniparental Disomy ◽

Breathing Disorders ◽

Obstructive Sleep

Abstract Context Sleep-related breathing disorders (SRBD) are common in people with Prader-Willi syndrome (PWS). Young adults with PWS benefit from GH continuation after attaining adult height by maintaining the improved body composition obtained during childhood. There are, no studies about the effects of GH on SRBD in young adults with PWS who were treated with GH during childhood. Objective Investigate the effects of GH vs placebo on SRBD in young adults with PWS who were treated with GH during childhood and had attained adult height. Design Two-year, randomized, double-blind, placebo-controlled, crossover study in 27 young adults with PWS, stratified for sex and body mass index. Setting Dutch PWS Reference Center. Intervention Crossover intervention with GH (0.67 mg/m2/d) and placebo, both over one year. Main Outcome Measures Apnea hypopnea index (AHI), obstructive apnea index (OAI), central apnea index (CAI), measured by polysomnography. Results Compared with placebo, GH did not increase AHI, CAI, or OAI (P > 0.35). The effect of GH vs placebo was neither different between men and women, nor between patients with a deletion or maternal uniparental disomy/imprinting center defect. After two years, there was no difference in AHI, CAI, or OAI compared with baseline (P > 0.18). Two patients (7%) fulfilled the criteria of obstructive sleep apnea regardless of GH or placebo. Conclusions GH compared with placebo does not cause a substantial increase in AHI, CAI, or OAI in adults with PWS who were treated with GH during childhood and have attained adult height. Our findings are reassuring and prove that GH can be administered safely.

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Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome

Clinical Endocrinology ◽

10.1111/j.1365-2265.2011.04313.x ◽

2012 ◽

Vol 76 (6) ◽

pp. 843-850 ◽

Cited By ~ 28

Author(s):

Andrea Corrias ◽

Graziano Grugni ◽

Antonino Crinò ◽

Stefania Di Candia ◽

Patrizia Chiabotto ◽

...

Keyword(s):

Children And Adolescents ◽

Adrenal Insufficiency ◽

Prader Willi Syndrome ◽

Central Adrenal Insufficiency

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Central Adrenal Insufficiency Is Rare in Adults With Prader–Willi Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa168 ◽

2020 ◽

Vol 105 (7) ◽

pp. e2563-e2571 ◽

Cited By ~ 2

Author(s):

Anna G W Rosenberg ◽

Karlijn Pellikaan ◽

Christine Poitou ◽

Anthony P Goldstone ◽

Charlotte Høybye ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Outcome Measure ◽

Tolerance Test ◽

Pituitary Hormone ◽

Prader Willi Syndrome ◽

Insulin Tolerance ◽

Synacthen Test ◽

Central Adrenal Insufficiency ◽

Stress Dose ◽

Hydrocortisone Treatment

Abstract Context Prader–Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension—already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity—or even mortality. Objective To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT). Design Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645). Setting Outpatient clinic. Patients or Other Participants Eighty-two adults with genetically confirmed PWS. Main Outcome Measure For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient. Results Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism. Conclusions Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS.

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Abstract 17063: Sleep Related Breathing Disorders and Heart Rate Variability in Young and Healthy Adults From the General Population

Circulation ◽

10.1161/circ.132.suppl_3.17063 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Stefanie Aeschbacher ◽

Matthias Bossard ◽

Mirco von Rotz ◽

Tobias Schoen ◽

Anna Maseli ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Sleep Apnea ◽

Large Population ◽

Healthy Adults ◽

Apnea Hypopnea Index ◽

Sleep Related Breathing Disorders ◽

Breathing Disorders ◽

Relationship Of ◽

The Relationship

Background: The influence of sleep related breathing disorders on heart rate variability (HRV), a measure of autonomic nervous function, is not well studied. We therefore assessed the relationship of the Apnea-Hypopnea Index (AHI) and the Oxygen Desaturation Index (ODI) with 24-hour HRV in a large population of young and healthy adults. Methods: Individuals aged between 25-41 years with a body mass index ≤35km/kg2 and without known sleep apnea syndrome (SAS) or cardiovascular disease were included in the population-based GAPP-study. A 24-hour electrocardiogram (ECG) was obtained in every participant, and systematic post-processing performed with a dedicated software. The standard deviation of all normal RR intervals (SDNN) was used as main HRV marker. AHI and ODI were obtained from nighttime pulsoxymetry with nasal airflow measurements. Sleep apnea (SA) was defined as either an AHI ≥5 or an ODI ≥5. Multivariable regression models were constructed to assess the relationship of SDNN with either AHI or ODI and to adjust for a large number of confounders. Results: We included 1266 participants (47% men) with a median age of 35 years. Mean SDNN among men and women was 162 and 148ms (p<0.0001), respectively. The proportion of participants with SA using an AHI- or ODI-based definition was 10 and 11%, respectively. Compared to individuals without SA, the beta coefficient (95% confidence interval (CI)) for SDNN was -7.48 (-14.75; -0.23, p=0.04) among those with an AHI-based SA definition, and was -11.45 (-18.39; -4.52, p=0.001) among those with an ODI-based SA definition. A highly significant inverse trend across different categories of AHI and ODI was observed, as shown in the Table. Conclusion: Early stages of sleep related breathing disorders are strongly associated with decreasing HRV in young and healthy adults, without evidence of a threshold. These findings suggest a tight link between sleep related breathing disorders and autonomic dysfunction.

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