Precocious puberty: diagnosis and management

Precocious puberty is commonly defined as puberty that starts before age 8 years in girls and 9 years in boys. The causes of it may range from a variant of normal development to various pathologic conditions. The etiology of precocious puberty is classified by the underlying pathogenesis into gonadotropin dependent central precocious puberty and peripheral precocious puberty which is independent of gonadotropin but due to different other causes. Variants of precocious puberty include premature thelarche, premature puberche and isolated premature menarche which imply onset of isolated changes without any other signs of sexual development. Precocious puberty might have an impact on final stature owing to premature epiphyseal fusion and also it has got influence on psychosocial wellbeing. Evaluation includes a detailed history, physical examination, biochemical testing and imaging directed towards suspected etiology. Gonadotropin releasing hormone (GnRH) analogues are effective for treatment of central precocious puberty. Treatment of peripheral precocious puberty should be based on the specific cause. Pubertal variants are usually non-progressive and need no treatment but should be monitored carefully. BIRDEM Med J 2022; 12(1): 62-69

Distinct Gut Microbiota Structure and Function of Children With Idiopathic Central and Peripheral Precocious Puberty

BackgroundPrecocious puberty (PP) is one of the most common endocrine diseases in children, and the pathogenesis is currently unknown. Recent studies on the gut-brain axis have shown that there is a correlation between childhood endocrine diseases and the gut microbiota (GM). However, whether there is a correlation between children’s GM with different types of PP remains unclear.ResultsTo explore the GM characteristics of children with different types of PP, we recruited 27 idiopathic central precocious puberty children (ICPP group), 18 peripheral precocious puberty children (PPP group) and 23 healthy children of the same age (HC group). Their stool samples were subjected to 16S rDNA sequencing. In this study, we found that the OTUs numbers, the annotated genera and α-diversity of GM of ICPP and PPP group were all significantly higher than that in HC group (P < 0.05). The abundance of butyrate acid producing bacteria, such as Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus and Alistipes, were significantly higher in ICPP and PPP group, while Bacteroides and Faecalibacterium were significantly higher in HC group. The GM symbiosis network showed that both Bacteroides and Faecalibacterium were negatively correlated with these butyrate-acid producing bacteria. The abundances of most significantly changed genera were gradually increased from HC to PPP, and to ICPP group, while only Bacteroides was gradually decreased. After the prediction of the metabolic pathways of the GM, cell motility, signal transduction and environmental adaptation were significantly enriched in the ICPP and PPP groups (P < 0.05), while the carbohydrate metabolism pathway were significantly decreased (P < 0.001). ConclusionsOverall, this study showed that the GM composition and functional pattern of children with ICPP and PPP are different from healthy children, and PPP may be a transitional stage between ICPP and HC children, which provide a theoretical basis for clinical intervention based on GM in the treatment of PP.

Pathophysiology of Peripheral Precocious Puberty in girls: an overview

Precocious puberty can be distinguished in central, or peripheral, based on the presence or absence of the Hypothalamic- Pituitary- Gonadal axis activation. The pathogenesis of peripheral precocious puberty (PPP) is based mainly on excessive estrogenic exposure, either endogenous or exogenous. The congenital causes of PPP include McCune- Albright syndrome (MAS) and Congenital Adrenal Hyperplasia (CAH). The main causes of acquired PPP are oestrogen producing tumours, which are mainly of ovarian or adrenal origin, hypothyroidism and environmental oestrogens or substances with estrogenic function.

Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl

Sex hormone-binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient’s SHBG level was remarkably low for her age, at less than 5 nmol/L [reference range for a girl with a bone age of 10 years, 73 nmol/L (SEM= 10)](1). Upon genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554 C&gt;T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient’s phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.

Peripheral Precocious Puberty of Ovarian Origin in a Series of 18 Girls: Exome Study Finds Variants in Genes Responsible for Hypogonadotropic Hypogonadism

Background: Peripheral precocious puberty of ovarian origin is a very rare condition compared to central form. It may be associated with an isolated ovarian cyst (OC). The causes of OC in otherwise healthy prepubertal girls is currently unknown.Methods: Exome sequencing was performed on a cohort of 18 unrelated girls presenting with prenatal and/or prepubertal OC at pelvic ultrasonography. The presenting symptom was prenatal OC in 5, breast development in 7 (with vaginal bleeding in 3) and isolated vaginal bleeding in 6. All had OC ≥ 10 mm. The girls had no other anomalies. Four patients had a familial history of ovarian anomalies and/or infertility.Results: In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including PNPLA6, SEMA3A, TACR3, PROK2, KDM6A, KMT2D, OFD1, GNRH1, GNRHR, GLI3, INSR, CHD7, CDON, RNF216, PROKR2, GLI3, LEPR. Basal plasma concentrations of gonadotropins were undetectable and did not increase after gonadotropin-releasing hormone test in 3 of them whilst 5 had prepubertal values. The plasma estradiol concentrations were prepubertal in 6 girls, high (576 pmol/L) in one and not evaluated in 2 of them.Conclusions: In the first study reporting exome sequencing in prepubertal OC, half of the patients with OC carry either previously reported pathogenic variants or potentially pathogenic variants in genes known to be associated with isolated or syndromic forms of congenital hypogonadotropic hypogonadism. Functional studies and studies of other cohorts are recommended to establish the causality of these variants.

Central precocious puberty after resection of a virilising adrenocortical oncocytic tumour

Adrenocortical oncocytic tumours are a histological subtype of adrenal neoplasms with a distinctive morphological appearance. Since these tumours are composed of cells of the adrenal cortex, they may act as functional tumours with excess hormone production. They may cause Cushing’s syndrome, inappropriate virilisation or precocious puberty. Though rare during childhood, adrenocortical oncocytic tumours should be suspected in a child with peripheral precocious puberty and marked elevation of dehydroepiandrosterone sulfate levels. We describe a 6-year girl who presented with peripheral precocious puberty due to a functional adrenocortical oncocytic tumour. Three months after tumour removal, she developed true central precocious puberty. This report highlights that peripheral precocious puberty may trigger central precocious puberty, particularly after resolution of the underlying cause of the peripheral precocious puberty.

Central Precocious Puberty as a Complication of Congenital Adrenal Hyperplasia in a Boy: Case Report

Precocious puberty has intense influence on physical and psychosocial well-being of affected children and raises a lot of concerns as well as uncertainties in family.Here,we report a case of Central precocious puberty (CPP)superimposed on peripheral precocious puberty (PPP) due to congenital adrenal hyperplasia(CAH). Bangladesh J Child Health 2020; VOL 44 (3) :184-187