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Table of Contents
Year : 2022  |  Volume : 19  |  Issue : 2  |  Page : 123-125

Hypothyroidism in paediatric patients with Prader-Willi syndrome; regular monitoring is recommended

1 Paediatric Endocrine and Diabetes Unit, Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman; Paediatric Department, Faculty of Medicine, Wasit University, Kut, Iraq
2 Paediatric Department, College of Medicine, Al-Mustansiriyah University, Baghdad, Iraq

Date of Submission04-Mar-2022
Date of Acceptance15-Mar-2022
Date of Web Publication30-Jun-2022

Correspondence Address:
Wasnaa Hadi Abdullah
Paediatric Department, College of Medicine, Al-Mustansiriyah University, Baghdad
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/MJBL.MJBL_43_22

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Prader-Willi syndrome (PWS) is a genetic disorder described by multifaceted clinical features with implications on the endocrine system, metabolism, and behavior. Some symptoms of PWS syndrome can be confused with the relative clinical aspects of hypothyroidism, such as lethargy, muscular hypotonia, and poor sucking ability. In this review, we would like to enlighten the importance of checking thyroid function in PWS patients at birth, at least annually, in those on growth hormone (GH) treatment, in any child of PWS with growth failure, and in those in whom there is an insufficient response to GH therapy, to ensure that any aberrant thyroid function is not overlooked and adequately treated.

Keywords: Growth hormone, hypothyroidism, Prader-Willi syndrome, thyroid function

How to cite this article:
Alsaffar H, Abdullah WH, Hussein SA. Hypothyroidism in paediatric patients with Prader-Willi syndrome; regular monitoring is recommended. Med J Babylon 2022;19:123-5

How to cite this URL:
Alsaffar H, Abdullah WH, Hussein SA. Hypothyroidism in paediatric patients with Prader-Willi syndrome; regular monitoring is recommended. Med J Babylon [serial online] 2022 [cited 2023 May 29];19:123-5. Available from: https://www.medjbabylon.org/text.asp?2022/19/2/123/349485

  Background Top

Prader-Willi syndrome (PWS), first reported in 1956 by Prader, Labhart, and Willi, is a genetic syndrome with a variety of clinical manifestations[1] with implications on the endocrine system, metabolism, and behavior.[2] It is the most frequent form of syndromic obesity, and it influences both genders equally.[3] PWS results from a loss of a region of the 15q11-13 chromosome that is inherited paternally because of deletion, imprinting problems, maternal uniparental disomy, or chromosomal translocations.[4]

  Clinical Features of PWS Top

PWS is distinguished by neonatal hypotonia that may continue through infantile age and feeding problems that result in a failure to thrive initially. Later, gaining an interest in food, followed by hyperphagia, which leads to weight gain at an early age that could easily progress to severe obesity. Other features include cognitive disorders, speech problems, psychiatric disorders, and characteristic dysmorphic features including facial manifestations such as small mouth associated with thin upper lip with downturned corners, palpebral fissures of upslanting nature, and small hands and feet.[5] The risk of PWS among a child’s siblings with PWS is determined by the sort of molecular abnormality that causes PWS in that child. As a result, genetic testing is critical not only for confirming the diagnosis of PWS but also for determining the risk of recurrence in subsequent pregnancies.[6]

PWS patients have hypothalamic dysfunction, which can result in growth hormone (GH) deficit, central hypothyroidism, central adrenal insufficiency, hypogonadism, and low bone mineral density, among other endocrinopathies.[3] As a result, children with PWS need to be closely monitored by an endocrinologist throughout their lives, from the infantile period to adulthood.[2]

  Hypothyroidism in PWS Top

The prevalence of hypothyroidism in PWS has been described in a variety of ways. According to some estimates, 20%–30% of patients are affected[7]; others, however, have observed that it is prevalent in just 2%–4% of the PWS population, which is comparable to healthy controls or the general population.[8],[9] However, in a study of 18 children with PWS under the age of 2 years, Vaiani et al.[10] discovered low blood levels of total T4 and/or free T4 without a compensatory increase in serum thyroid stimulating hormone (TSH) in 72% of the studied infant patients, signifying that hypothalamic pituitary thyroid axis impairment is a prominent component in PWS throughout the infantile period.

Interestingly, when comparing PWS patients with healthy controls, Sharkia et al. reported no significant difference in total T4 and TSH levels on newborn screening of both groups. Furthermore, performing a thyrotropin-releasing hormone stimulation test in the same cohort of patients did not show any cases of central hypothyroidism.[9] According to this research, it is possible that central hypothyroidism does not exist at birth but develop later on; therefore, neonatal metabolic screening alone is insufficient to detect it[11] and it is strongly advised that thyroid function test ought to be performed during the first 3 months of child age and then every year after that, particularly if the patient was on GH medication.[12] Moreover, any PWS child with growth failure or decreased bone density, as well as those who do not respond well to GH therapy, should be tested for hypothyroidism.[12]

Thyroid hormone concentrations may be normal in PWS, but these observations could be confounded by the presence of obesity, which can cause a mild, reversible elevation of TSH,[7],[13],[14] and even later, anecdotal occurrences of congenital hypothyroidism in PWS neonates related to an ectopic sublingual thyroid gland and fetal goiter have been reported in the literature.[5]

From another point of view, as there is growing evidence that body composition has an impact on thyroid hormone levels,[15],[16],[17] thyroid function in PWS patients might be influenced by poor nutritional status, low body weight of children, and low body mass index, which are common in infants with PWS. As a result, during the infancy period, comparisons between PWS participants and healthy controls children may result in bias, leading to misreadings of thyroid function test in infants with PWS. Furthermore, because GH treatment has been reported to promote T4 to T3 conversion and lower T4 levels, a united evaluation of GH-treated and GH-untreated participants may result in thyroid hormone status misconceptions in PWS.[1]

Festen et al.[15] conducted a study of 79 children with PWS, which showed decreases in free T4 after starting GH treatment; however, TSH remained normal and total T3 levels were normal or in the high normal range implying that T4 to T3 conversion in PWS children has increased. This conclusion point sheds the light to the importance of assessing thyroid function before starting GH and regularly thereafter, while the patient is receiving GH treatment.

  Conclusion Top

Hypothalamic dysfunction occurs in PWS patients, which can lead to a variety of endocrinopathies, including hypothyroidism. Moreover, some studies have reported the occurrence of congenital hypothyroidism in PWS. It is worthwhile to enlighten the importance of checking thyroid function in PWS patients at birth, at least annually, in those on GH treatment, in any child of PWS with growth failure, and in those in whom there is an insufficient response to GH therapy, to ensure that any aberrant thyroid function is not overlooked and adequately treated.

Ethical approval

Not applicable.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Konishi A, Ida S, Shoji Y, Etani Y, Kawai M Central hypothyroidism improves with age in very young children with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2021;94:384-91.  Back to cited text no. 1
Heksch R, Kamboj M, Anglin K, Obrynba K Review of Prader-Willi syndrome: The endocrine approach. Transl Pediatr 2017;6:274-85.  Back to cited text no. 2
Butler MG, Hanchett JM, Thompson T Clinical findings and natural history of Prader-Willi syndrome. In: Butler MG, Lee PDK, Whitman BY, editors. Management of Prader-Willi Syndrome. New York: Springer; 2006. p. 7-9.  Back to cited text no. 3
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ Prader-Willi syndrome. Genet Med 2012;14:10-26.  Back to cited text no. 4
Muscogiuri G, Formoso G, Pugliese G, Ruggeri RM, Scarano E Prader-Willi syndrome : An uptodate on endocrine and metabolic complications. Rev Endocr Metab Disord 2019;15:239-50.  Back to cited text no. 5
Carroll JE, Irwin MR, Seeman TE, Diez-Roux AV, Prather AA, Olmstead R, et al. Obstructive sleep apnea, nighttime arousals, and leukocyte telomere length: The multi-ethnic study of atherosclerosis. Sleep 2019;42:zsz089.  Back to cited text no. 6
Tauber M, Barbeau C, Jouret B, Pienkowski C, Malzac P, Moncla A, et al. Auxological and endocrine evolution of 28 children with Prader-Willi syndrome: Effect of GH therapy in 14 children. Horm Res 2000;53:279-87.  Back to cited text no. 7
Butler MG, Theodoro M, Skouse JD Thyroid function studies in Prader-Willi syndrome. Am J Med Genet A 2007;143A:488-92.  Back to cited text no. 8
Sharkia M, Michaud S, Berthier MT, Giguère Y, Stewart L, Deladoëy J, et al. Thyroid function from birth to adolescence in Prader-Willi syndrome. J Pediatr 2013;163:800-5.  Back to cited text no. 9
Vaiani E, Herzovich V, Chaler E, Chertkoff L, Rivarola MA, Torrado M, et al. Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of life. Clin Endocrinol (Oxf) 2010;73:546-50.  Back to cited text no. 10
Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M; Speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab 2008;93:4183-97.  Back to cited text no. 11
Cataletto MAAMGBME. Prader-Willi syndrome : A review of clinical, genetic, and endocrine findings. J Endocrinol Invest 2015;38:1249-63.  Back to cited text no. 12
Pellikaan K, Rosenberg AG, Kattentidt-Mouravieva AA, Kersseboom R, Bos-Roubos AG, Veen-Roelofs JM, et al. Missed diagnoses and health problems in adults with Prader-Willi syndrome: Recommendations for screening and treatment. J Clin Endocrinol Metab 2020;105:e4671-87.  Back to cited text no. 13
Iughetti L, Vivi G, Balsamo A, Corrias A, Crinò A, Delvecchio M, et al. Thyroid function in patients with Prader-Willi syndrome: An Italian multicenter study of 339 patients. J Pediatr Endocrinol Metab 2019;32:159-65.  Back to cited text no. 14
Festen DA, Visser TJ, Otten BJ, Wit JM, Duivenvoorden HJ, Hokken-Koelega AC Thyroid hormone levels in children with Prader-Willi syndrome before and during growth hormone treatment. Clin Endocrinol (Oxf) 2007;67:449-56.  Back to cited text no. 15
Jin HY Prevalence of subclinical hypothyroidism in obese children or adolescents and association between thyroid hormone and the components of metabolic syndrome. J Paediatr Child Health 2018;54:975-80.  Back to cited text no. 16
Lundbäck V, Ekbom K, Hagman E, Dahlman I, Marcus C Thyroid-stimulating hormone, degree of obesity, and metabolic risk markers in a cohort of Swedish children with obesity. Horm Res Paediatr 2017;88:140-6.  Back to cited text no. 17


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