Idiopathic central precocious puberty with Prader–Willi syndrome: pubertal development with discontinuation of gonadotropin-releasing hormone analog

Abstract

Summary Prader–Willi syndrome (PWS) is a genetic imprinting disorder that is characterized by obesity, short stature, and hypogonadism. Hypogonadism is characterized by normal luteinizing hormone (LH), high follicle-stimulating hormone (FSH), low testosterone, low inhibin B, and relatively low anti-Müllerian hormone (AMH). Only a few cases of central precocious puberty (CPP) have been reported in PWS, and follow-up for CPP with PWS is not established. Hence, we present a boy with PWS accompanied by CPP. Gonadotropin-releasing hormone analog (GnRHa) therapy was started at 7 years of age, CPP was adequately arrested, and GnRHa therapy was discontinued at 11.3 years of age. Growth hormone (GH) therapy was started at 12 years of age due to inadequate growth. He grew close to his final height, and his testes developed with normal LH, increased FSH, normal testosterone, and reduced AMH corresponding to puberty at 13.5 years of age. The features of 16 patients with PWS with CPP, including our patient, were summarized. Out of seven male patients, five were treated with GnRHa, as well as four out of nine female patients. Out of 16 patients, 6 were assessed with pubertal development over 13 years of age. Pubertal development was considered to be restored in four patients who had GnRHa therapy discontinuation. We should carefully follow-up on pubertal development in CPP. GnRHa therapy is useful for adequate puberty blockage, and pubertal development could be restored with GnRHa therapy discontinuation. Learning points Pubertal development in Prader–Willi syndrome (PWS) varies from hypogonadism to precocious puberty. Pubertal development assessment based on clinical features and hormone levels is needed in central precocious puberty (CPP) treatment with PWS. Gonadotropin-releasing hormone analog (GnRHa) therapy is useful for CPP with PWS, and pubertal development can be restored with GnRHa therapy discontinuation.

Central precocious puberty in Prader-Willi syndrome: a narrative review

“…We sought to summarize the following outcome measures from the reviewed articles: We identified a total of 22 children with CPP and genetically confirmed Prader-Willi syndrome mostly in case reports and abstracts, summarizing 13 children from case reports and case studies [13][14][15][16][17][18][19][20][21][22] and 9 children from Embase indexed abstracts [23][24][25][26][27]. There were 13 (59%) male patients and 9 (41%) female cases, with mean age at CPP onset of 7,64 +/-1,01 years (5 -9 years).…”

“…However, exceptional cases leading up to pregnancy have been described (6), isolated premature pubarche is reported in 14% of cases (1). Despite most PWS patients having hypogonadism, a few cases of central precocious puberty (CPP) have been reported (16).…”

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

“…While hypogonadism is the most common change in the pituitary-gonadal axis, CPP, though rare, has been documented in children with PWS and could be linked to loss-of-function variations in the MKRN3 gene at the 15q11-q13 locus (228,229). The MKRN3 gene is widely recognized as a cause of CPP in the general population (230).…”

“…Alternatively, high levels of 17-hydroxyprogesterone and DHEA sulfate were found in patients with CPP, suggesting elevated adrenal androgen levels as previously reported in PWS. Therefore, a combination of a father-derived MKRN3 allele deletion, basal adrenarche, and hypothalamic-pituitary acceleration may play a role in the early onset of precocious puberty (229). The type of hypogonadism -hypogonadotropic, hypergonadotropic, or a mix of these -only becomes apparent in late adolescence or early adulthood and appears to stabilize after the age of 20 years (225).…”

Analysis of the efficacy of Dabuyin pill combined with gonadotropin-releasing hormone analogue in the treatment of central precocious puberty girls based on network pharmacology

“…Although these drugs are effective, they are not accepted by most patients because of their high price. Traditional Chinese medicine (TCM) believes that CPP is affected by the above factors, resulting in imbalance of Yin and Yang of the "kidney", kidney Yin deficiency, and phase fire, and Dabuyin pill is a recipe for nourishing Yin and reducing fire (12)(13)(14).…”