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The Journal of Clinical Endocrinology... Jul 2023Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic-pituitary-gonadal axis with onset of sexual development before the age of...
Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic-pituitary-gonadal axis with onset of sexual development before the age of 8 years in girls and 9 years in boys. A decrease in the age of thelarche has been reported over the past several decades; however, the tempo of pubertal progression can be slower and adult height may not be adversely affected in many of the girls who experience thelarche at 6-8 years. Outside of this secular trend in the development itself, the past several decades have also brought about advances in diagnosis and management. This includes the widespread use of an ultrasensitive luteinizing hormone assay, decreasing the need for stimulation testing and a better understanding of the genetics that govern the onset of puberty. Additionally, management of CPP using gonadotropin-releasing hormone analogs (GnRHas) has changed with the advent of new longer-acting formulations. Emerging long-term outcomes of GnRHa administration with regards to obesity, cardiovascular risk factors and fertility are reassuring. Despite these advancements, clinical care in CPP is hampered by the lack of well-designed controlled studies, and management decisions are frequently not supported by clear practice guidelines. Data in boys with CPP are limited and this article focuses on the diagnosis and management of CPP in girls, particularly, in those who present with thelarche at the age of 6-8 years.
Topics: Female; Male; Humans; Child; Gonadotropin-Releasing Hormone; Puberty, Precocious; Sexual Development; Fertility; Heart Disease Risk Factors; Follicle Stimulating Hormone
PubMed: 36916130
DOI: 10.1210/clinem/dgad081 -
BMC Pediatrics Nov 2021Obesity is an important underlying cause of central precocious puberty (CPP), but previous large studies are flawed by using just age and breast examination to diagnose...
BACKGROUND
Obesity is an important underlying cause of central precocious puberty (CPP), but previous large studies are flawed by using just age and breast examination to diagnose CPP. We aimed to determine whether overweight and obesity in childhood increases hormonally diagnosed CPP.
METHODS
Our retrospective, case-control study recruited 846 children diagnosed as having CPP and randomly sampled 1650 healthy control subjects in Xingtai Third Hospital in China between November 2018 and March 2021. Information was obtained from an electronic medical record and questionnaire investigated in the outpatient visit. Observations were made before the a priori hypothesis. Unconditional logistic regression for analysis was used to determine whether overweight and obesity status and duration of overweight/obesity were associated with CPP.
RESULTS
Overweight and obesity were significantly associated with increased odds of CPP among girls, even after adjusting for birth weight, exclusive breastfeeding for 6 month, household income, maternal overweight, paternal overweight, and maternal menarche age (overweight: the adjusted odds ratio (aOR) (95%CI): 1.92 (1.16, 3.24), p = 0.02; obesity: aOR (95%CI): 1.78 (1.13, 3.48), p = 0.03). Furthermore, the effects of overweight and obesity were significant when ongoing for 1 to 2 years, 2 to 3 years, and greater than 3 years, but not at less than 1 year. For boys, association between obesity and increased odds of CPP was observed (aOR (95%CI): 1.68 (1.09, 3.75), p = 0.03). The effects of overweight and/or obesity were only significant when ongoing for greater than 2 years.
CONCLUSIONS
Prolonged overweight and obesity in early childhood may be risk factors for CPP, especially in girls. Weight loss might be an important approach for the prevention of precocious puberty in children.
Topics: Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Pediatric Obesity; Puberty, Precocious; Retrospective Studies; Risk Factors
PubMed: 34784914
DOI: 10.1186/s12887-021-02936-1 -
International Journal of Molecular... May 2023McCune-Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning... (Review)
Review
McCune-Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning endocrinopathies. The molecular basis of MAS has been ascribed to the post-zygotic somatic gain-of-function mutations in the gene, which encodes the alpha subunit of G proteins, leading to constitutive activation of several G Protein-Coupled Receptors (GPCRs). The co-occurrence of two of the above-mentioned cardinal clinical manifestations sets the diagnosis at the clinical level. In this case report, we describe a 27-month-old girl who presented with gonadotropin-independent precocious puberty secondary to an estrogen-secreting ovarian cyst, a café au lait skin macule and growth hormone, and prolactin excess, and we provide an updated review of the scientific literature on the clinical features, diagnostic work-up, and therapeutic management of MAS.
Topics: Female; Humans; Child, Preschool; Fibrous Dysplasia, Polyostotic; Puberty, Precocious; Endocrine System Diseases; Human Growth Hormone; Cafe-au-Lait Spots
PubMed: 37239810
DOI: 10.3390/ijms24108464 -
Current Opinion in Obstetrics &... Oct 2014Precocious puberty continues to elicit great interest and concern among medical practitioners, as well as the public. (Review)
Review
PURPOSE OF REVIEW
Precocious puberty continues to elicit great interest and concern among medical practitioners, as well as the public.
RECENT FINDINGS
Studies have elucidated neural regulation of puberty by kisspeptin, neurokinin B, and other factors. Cohort studies from the North America and Europe suggest that the age of thelarche may be earlier than determined 2 decades ago, and menarche may be slightly earlier, but the causes are unclear. Long-term outcomes of gonadotropin-releasing hormone analog therapy demonstrate increases in final height in the youngest treated patients, with no apparent adverse bone or reproductive consequences.
SUMMARY
Although the appropriate threshold age of onset of central puberty remains uncertain, gonadotropin-releasing hormone analog therapy is well tolerated and effective in suppressing luteinizing hormone pulses and ovarian activity.
Topics: Body Height; Body Weight; Bone Density; Child; Female; Gonadotropin-Releasing Hormone; Humans; Incidence; Puberty, Precocious; Sexual Maturation
PubMed: 25144596
DOI: 10.1097/GCO.0000000000000099 -
Pediatric Annals Jan 2018Premature thelarche is a benign condition that affects young girls and may be interpreted as a sign of central precocious puberty (CPP). Parental concern is common when... (Review)
Review
Premature thelarche is a benign condition that affects young girls and may be interpreted as a sign of central precocious puberty (CPP). Parental concern is common when breast development is noted in a young girl. It is important to differentiate premature thelarche from CPP, as the latter is a more serious disorder that may affect final adult height and menarcheal age, and may have psychological implications as well. Distinguishing between the two conditions clinically may help the patients avoid unnecessary testing. Pediatricians can play a pivotal role by providing reassurance to families and helping alleviate parental anxiety. This article reviews the clinical presentation of premature thelarche, its usual course, and implications. [Pediatr Ann. 2018;47(1):e12-e15.].
Topics: Breast; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Puberty; Puberty, Precocious
PubMed: 29323691
DOI: 10.3928/19382359-20171214-01 -
Journal of Pediatric and Adolescent... Oct 2023Prepubertal bleeding is a common presentation in the pediatric office and can be distressing for patients and families. A comprehensive approach to diagnosis and... (Review)
Review
BACKGROUND
Prepubertal bleeding is a common presentation in the pediatric office and can be distressing for patients and families. A comprehensive approach to diagnosis and management allows clinicians to identify patients at risk for worrisome pathology and arrange timely care.
OBJECTIVE
We aimed to review the key features of clinical history, physical exam, and diagnostic workup of a child presenting with prepubertal bleeding. We reviewed potential pathologies requiring urgent investigations and management, such as precocious puberty and malignancy, as well as more common etiologies, including foreign bodies and vulvovaginitis.
CONCLUSION
Clinicians should approach each patient with the goal of excluding diagnoses that require urgent interventions. A thoughtful clinical history and physical exam can inform appropriate investigations to optimize patient care.
Topics: Female; Child; Humans; Uterine Hemorrhage; Vulvovaginitis; Foreign Bodies; Physical Examination; Puberty, Precocious
PubMed: 37301426
DOI: 10.1016/j.jpag.2023.06.002 -
Seminars in Reproductive Medicine Mar 2022Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of... (Review)
Review
Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.
Topics: Female; Gonadotropin-Releasing Hormone; Humans; Menarche; Puberty; Puberty, Delayed; Puberty, Precocious
PubMed: 34560809
DOI: 10.1055/s-0041-1735892 -
Primary Care Jun 2020Evaluation of the child with abnormal pubertal development can be challenging for the primary care provider. Understanding the factors associated with timing of pubertal... (Review)
Review
Evaluation of the child with abnormal pubertal development can be challenging for the primary care provider. Understanding the factors associated with timing of pubertal onset and the normal sequence of pubertal changes is useful in evaluation of children with puberty disorders. A thorough workup includes assessment of growth rate, Tanner staging, and rate of pubertal progression, in addition to an extensive history and physical examination to identify signs and symptoms of disorders associated with abnormal pubertal timing. Initial diagnostic studies will most often include a bone age, levels of gonadotropins, and levels of estradiol (for girls) or testosterone (for boys).
Topics: Child; Female; Gonadal Disorders; Gonadal Steroid Hormones; Humans; Hypogonadism; Male; Primary Health Care; Puberty, Delayed; Puberty, Precocious
PubMed: 32423709
DOI: 10.1016/j.pop.2020.02.001 -
Current Opinion in Pediatrics Aug 2018To summarize advances in the genetics underlying variation in normal pubertal timing, precocious puberty, and delayed puberty, and to discuss mechanisms by which genes... (Review)
Review
PURPOSE OF REVIEW
To summarize advances in the genetics underlying variation in normal pubertal timing, precocious puberty, and delayed puberty, and to discuss mechanisms by which genes may regulate pubertal timing.
RECENT FINDINGS
Genome-wide association studies have identified hundreds of loci that affect pubertal timing in the general population in both sexes and across ethnic groups. Single genes have been implicated in both precocious and delayed puberty. Potential mechanisms for how these genetic loci influence pubertal timing may include effects on the development and function of the GnRH neuronal network and the responsiveness of end-organs.
SUMMARY
There has been significant progress in identifying genetic loci that affect normal pubertal timing, and the first single-gene causes of precocious and delayed puberty are being described. How these genes influence pubertal timing remains to be determined.
Topics: Adolescent; Age Factors; Child; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Puberty; Puberty, Delayed; Puberty, Precocious
PubMed: 29771761
DOI: 10.1097/MOP.0000000000000642 -
Pediatric Annals Jan 2018Adrenarche is when a child's adrenal cortex starts to secrete adrenal androgen precursors. Dehydroepiandrosterone (DHEA) is the most abundant product of the adrenal... (Review)
Review
Adrenarche is when a child's adrenal cortex starts to secrete adrenal androgen precursors. Dehydroepiandrosterone (DHEA) is the most abundant product of the adrenal cortex, and is a weak androgen agonist thought to be responsible for the clinical signs of pubarche by conversion to more potent androgens, testosterone, and dihydrotestosterone. DHEA's extra-adrenal sulfation product, dehydroepiandrosterone sulfate, is a stable marker for adrenal androgenic activity. Pubarche is the physical manifestation of androgenic hormone production, and includes the development of pubic and axillary hair, adult body odor, and acne. This stage is usually considered premature if it commences before age 8 years in girls or age 9 years in boys. Premature adrenarche is a diagnosis of exclusion, as true centrally mediated precocious puberty, congenital adrenal hyperplasia, exogenous androgen exposure, and androgen-secreting tumors must be ruled out. Premature adrenarche may be associated with a history of an infant who was small for gestational age at birth who then gained weight rapidly thereafter or became obese. In some instances, premature adrenarche may predict functional ovarian hyperandrogenism in adolescence. Management of premature adrenarche is largely aimed at observation, lifestyle adjustments for weight concerns, and monitoring for future possible persistent androgen excess and insulin resistance. [Pediatr Ann. 2018;47(1):e7-e11.].
Topics: Adrenarche; Child; Diagnosis, Differential; Female; Humans; Male; Prognosis; Puberty, Precocious
PubMed: 29323690
DOI: 10.3928/19382359-20171214-04