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

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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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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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

Journal of Clinical Medicine ◽

10.3390/jcm10245781 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5781

Author(s):

Karlijn Pellikaan ◽

Yassine Ben Brahim ◽

Anna G. W. Rosenberg ◽

Kirsten Davidse ◽

Christine Poitou ◽

...

Keyword(s):

Cohort Study ◽

Expert Panel ◽

Panel Discussion ◽

Pituitary Hormone ◽

Prader Willi Syndrome ◽

International Expert ◽

Medical File ◽

Genetic Syndrome ◽

Clinical Recommendations ◽

Medical Questionnaire

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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Effects of growth hormone treatment in adults with Prader–Willi syndrome

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2013.01.001 ◽

2013 ◽

Vol 23 (3) ◽

pp. 81-87 ◽

Cited By ~ 26

Author(s):

M.G. Butler ◽

B.K. Smith ◽

J. Lee ◽

C. Gibson ◽

C. Schmoll ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Treatment ◽

Hormone Treatment ◽

Prader Willi Syndrome

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Endocrine and metabolic aspects of adult Prader–Willi syndrome with special emphasis on the effect of growth hormone treatment

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2003.09.003 ◽

2004 ◽

Vol 14 (1) ◽

pp. 1-15 ◽

Cited By ~ 68

Author(s):

Charlotte Höybye

Keyword(s):

Growth Hormone ◽

Growth Hormone Treatment ◽

Hormone Treatment ◽

Prader Willi Syndrome

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Low FT4 Concentrations around the Start of Recombinant Human Growth Hormone Treatment: Predictor of Congenital Structural Hypothalamic-Pituitary Abnormalities?

Hormone Research in Paediatrics ◽

10.1159/000486033 ◽

2018 ◽

Vol 89 (2) ◽

pp. 98-107 ◽

Cited By ~ 5

Author(s):

Laura van Iersel ◽

Hanneke M. van Santen ◽

Gladys R.J. Zandwijken ◽

Nitash Zwaveling-Soonawala ◽

Anita C.S. Hokken-Koelega ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Treatment ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Hormone Treatment ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Gh Treatment ◽

Central Hypothyroidism ◽

Pituitary Disease

Background: Growth hormone (GH) treatment may unmask central hypothyroidism (CeH). This was first observed in children with GH deficiency (GHD), later also in adults with GHD due to acquired “organic” pituitary disease. We hypothesized that newly diagnosed CeH in children after starting GH treatment for nonacquired, apparent isolated GHD points to congenital “organic” pituitary disease. Methods: Nationwide, retrospective cohort study including all children with nonacquired GHD between 2001 and 2011 in The Netherlands. The prevalence of CeH, hypothalamic-pituitary (HP) abnormalities, and neonatal congenital hypothyroidism screening results were evaluated. Results: Twenty-three (6.3%) of 367 children with apparent isolated GHD were prescribed LT4 for presumed CeH within 2 years after starting GH treatment. Similarly to children already diagnosed with multiple pituitary hormone deficiency, 75% of these 23 had structural HP abnormalities. In children not prescribed LT4, low pre- or post-GH treatment FT4 concentrations were also associated with structural HP abnormalities. Neonatal screening results of only 4 of the 23 children could be retrieved. Conclusion: In children with nonacquired, apparent isolated GHD, a diagnosis of CeH after, or a low FT4 concentration around the start of GH treatment, is associated with congenital structural HP abnormalities, i.e., “organic” pituitary disease. Neonatal values could not be judged reliably.

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