Hypogonadism in Women with Prader-Willi Syndrome—Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion

Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.

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Hypogonadism in Adult Males with Prader-Willi Syndrome—Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion

Journal of Clinical Medicine ◽

10.3390/jcm10194361 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4361

Author(s):

Karlijn Pellikaan ◽

Yassine Ben Brahim ◽

Anna G. W. Rosenberg ◽

Kirsten Davidse ◽

Christine Poitou ◽

...

Keyword(s):

Expert Panel ◽

Panel Discussion ◽

Testosterone Replacement Therapy ◽

Male Hypogonadism ◽

Prader Willi Syndrome ◽

Adult Males ◽

Review Of The Literature ◽

International Expert ◽

Genetic Syndrome ◽

Dutch Cohort

Prader–Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.

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Thyroid Function in Adults with Prader–Willi Syndrome; a Cohort Study and Literature Review

Journal of Clinical Medicine ◽

10.3390/jcm10173804 ◽

2021 ◽

Vol 10 (17) ◽

pp. 3804

Author(s):

Karlijn Pellikaan ◽

Fleur Snijders ◽

Anna G. W. Rosenberg ◽

Kirsten Davidse ◽

Sjoerd A. A. van den Berg ◽

...

Keyword(s):

Metabolic Rate ◽

Basal Metabolic Rate ◽

Growth Hormone Treatment ◽

Hormone Treatment ◽

Thyroid Stimulating Hormone ◽

Pituitary Hormone ◽

Prader Willi Syndrome ◽

Negative Effects ◽

Medical File ◽

Genetic Syndrome

Prader–Willi syndrome (PWS) is a complex genetic syndrome combining hypotonia, hyperphagia, a PWS-specific neurocognitive phenotype, and pituitary hormone deficiencies, including hypothyroidism. The low muscle mass associated with PWS causes a low energy expenditure due to a low basal metabolic rate. Combined with increased energy intake due to hyperphagia, this results in a high risk of obesity and associated cardiovascular disease. To reduce the high mortality in PWS (3% yearly), exercise is extremely important. As hypothyroidism can impair exercise tolerance, early detection is crucial. We performed a literature search for articles on hypothyroidism in PWS, measured thyroid hormone (TH) levels in 122 adults with PWS, and performed a medical file search for medication use. Hypothyroidism (low free thyroxin) was present in 17%, and often central in origin (80%). Triiodothyronine levels were lower in patients who used psychotropic drugs, while other TH levels were similar. One in six patients in our cohort of adults with PWS had hypothyroidism, which is more than in non-PWS adults (3%). We recommend yearly screening of free thyroxin and thyroid-stimulating hormone levels to avoid the negative effects of untreated hypothyroidism on basal metabolic rate, body mass index, and cardiovascular risk. Additionally, we recommend measuring TH concentrations 3–4 months after the start of growth hormone treatment.

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Thyroid Function in Adults With Prader-Willi Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1741 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A853-A853

Author(s):

Karlijn Pellikaan ◽

Fleur Snijders ◽

Anna Gerarda Wilhelmina Rosenberg ◽

Aart Jan Van der Lely ◽

Laura de Graaff

Keyword(s):

Cardiovascular Risk ◽

Thyroid Hormone ◽

Thyroid Function ◽

Psychotropic Medication ◽

Psychotropic Drugs ◽

Exercise Intolerance ◽

Pituitary Hormone ◽

Prader Willi Syndrome ◽

Free T4 ◽

Genetic Syndrome

Abstract Introduction: Prader-Willi syndrome (PWS) is a complex genetic syndrome in which hypothalamic dysfunction leads to extreme appetite (hyperphagia) and pituitary hormone deficiencies (PHD), among others. Compared with the ‘general endocrine population’, the population of adults with PWS is characterized by a high prevalence of intellectual disability (ID) and frequent use of psychotropic drugs. Due to hypotonia and the low muscle mass associated with the syndrome, adults with PWS have a low basal metabolic rate (BMR) and a high risk of developing obesity. Therefore, exercising is extremely important. However, PHD like hypothyroidism can cause fatigue and exercise intolerance. If left untreated, hypothyroidism can lead to a further decrease in BMR, an increase in Body Mass Index (BMI) and increased cardiovascular risk. As mortality in PWS is high (3% yearly) and often related to cardiovascular problems and obesity, it is of utmost importance to optimize thyroid function and other factors affecting BMR. Methods: In 122 adults with PWS (median age 29 y [IQR 21-39], median BMI 29 kg/m2 [IQR 26-36]), we measured TSH, free T4 and T3 (the active form of thyroid hormone) and searched the medical history for use of medication and any pre-existing diagnosis of hypothyroidism. Moreover, we performed an extensive literature search and summarized the current literature on hypothyroidism, T3 and T4 levels in adults with PWS. Results: Hypothyroidism was present in 17% and more prevalent in females (23%) than in males (10%), even though this was not statistically significant (P=0.06). Although within the reference range, serum T3 levels were relatively high compared to free T4 levels. T3 levels were significantly lower in patients that used psychotropic medication (n=45) than in patients that did not (median 1.7 [IQR 1.5-2.0] vs 2.1 [IQR 1.7-2.3], P=0.013). Conclusion: We found a prevalence of hypothyroidism of 17% (compared to 3% in the non-PWS population). T3 levels were relatively high, which might be explained by increased peripheral conversion of T4 to T3 by deiodinase type 2. Levels of the active thyroid hormone T3 were significantly lower in patients using psychotropic medication. Based on our findings, we recommend 1) yearly screening of thyroid hormone levels in adults with PWS to avoid negative effects of untreated hypothyroidism on BMR, BMI and cardiovascular risk and 2) extra monitoring of the active thyroid hormone T3 in patients using psychotropic drugs.

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Pancreatic cancer treatment and research: an international expert panel discussion

Annals of Oncology ◽

10.1093/annonc/mdq545 ◽

2011 ◽

Vol 22 (7) ◽

pp. 1500-1506 ◽

Cited By ~ 32

Author(s):

M.A. Tempero ◽

J. Berlin ◽

M. Ducreux ◽

D. Haller ◽

P. Harper ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Treatment ◽

Expert Panel ◽

Panel Discussion ◽

International Expert

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A Microanalysis of the Decision Points in the Treatment of a Young Child:An International Expert Panel Presentation

PsycEXTRA Dataset ◽

10.1037/e608902012-107 ◽

2009 ◽

Author(s):

Frances S. Waters ◽

Robbie Adler-Tapia ◽

Renee Marks ◽

Sandra Baita

Keyword(s):

Expert Panel ◽

International Expert ◽

Decision Points

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Faculty Opinions recommendation of Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727041738.793527671 ◽

2017 ◽

Author(s):

Ruediger Hehlmann

Keyword(s):

Expert Panel ◽

International Expert ◽

Diagnosis And Management

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ISET Expert Panel Discussion Series 2020–2021

Journal of Special Education Technology ◽

10.1177/01626434211033589 ◽

2021 ◽

pp. 016264342110335

Author(s):

Emily Hoeh ◽

Tara L. Kaczorowski

Keyword(s):

Professional Development ◽

Special Education ◽

Information Sharing ◽

Expert Panel ◽

Panel Discussion ◽

Education Technology ◽

Technology Professional Development ◽

Individuals With Disabilities ◽

Technology Professional ◽

Development Committee

The Innovations and Special Education Technology Professional Development Committee would like to extend its appreciation to the following leaders in the field of Special Education. Each of the following individuals volunteered to speak during the 2020–2021 ISET Expert Panel Discussion series and shared expertise on a variety of pressing topics during remote instruction due to the COVID pandemic. The information sharing is a testament to their unwavering support for the members of ISET and all of the stakeholders involved in supporting individuals with disabilities.

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Effects of Childhood Multidisciplinary Care and Growth Hormone Treatment on Health Problems in Adults with Prader-Willi Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm10153250 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3250

Author(s):

Karlijn Pellikaan ◽

Anna G. W. Rosenberg ◽

Kirsten Davidse ◽

Anja A. Kattentidt-Mouravieva ◽

Rogier Kersseboom ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Treatment ◽

Multidisciplinary Care ◽

Hormone Treatment ◽

Health Problems ◽

Pituitary Hormone ◽

Childhood And Adolescence ◽

Prader Willi Syndrome ◽

Adult Age ◽

Beneficial Effects

Prader-Willi syndrome (PWS) is a complex hypothalamic disorder. Features of PWS include hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. The combination of growth hormone treatment and multidisciplinary care (GHMDc) has greatly improved the health of children with PWS. Little is known about the effects of childhood GHMDc on health outcomes in adulthood. We retrospectively collected clinical data of 109 adults with PWS. Thirty-nine had received GHMDc during childhood and adolescence (GHMDc+ group) and sixty-three had never received growth hormone treatment (GHt) nor multidisciplinary care (GHMDc− group). Our systematic screening revealed fewer undetected health problems in the GHMDc+ group (10%) than in the GHMDc− group (84%). All health problems revealed in the GHMDc+ group had developed between the last visit to the paediatric and the first visit to the adult clinic and/or did not require treatment. Mean BMI and the prevalence of diabetes mellitus type 2 were significantly lower in the GHMDc+ group compared to the GHMDc− group. As all patients who received GHt were treated in a multidisciplinary setting, it is unknown which effects are the result of GHt and which are the result of multidisciplinary care. However, our data clearly show that the combination of both has beneficial effects. Therefore, we recommend continuing GHMDc after patients with PWS have reached adult age.

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