Introduction
When a child reaches puberty, they often experience accelerated growth and the emergence of secondary sexual traits. It's a time of physical and psychological growth. Puberty begins and progresses as a result of a number of genetic, environmental, and dietary variables.
What Is the Physiology of Puberty?
Puberty is brought on by the hypothalamic-pituitary-gonadal (HPG) axis becoming active and maturing. The HPG axis briefly becomes activated at birth, increasing the amount of steroidal hormones produced. In both males and females, this stimulation may lead to pubic hair growth. The so-called "mini-puberty of infancy" regresses typically over the first two years of life. Although it is thought to be benign, there is very little knowledge regarding the aetiology and clinical importance of this condition.
The HPG axis then goes dormant until adolescence, when it is activated. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by the anterior pituitary gland in response to the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Male spermatogenesis and the release of testosterone are started by FSH, while female oogenesis and the release of estradiol are started by LH. Gonadarche is the term for the gonads' activation. A doctor should be knowledgeable with the terms used to describe pubertal development. Breast development, or thelarche, is a response to oestrogen. Pubarche, a reaction to androgens, is the growth of pubic hair. Adrenarche is the beginning of the production of adrenal androgen, which helps to cause pubarche.
What Is the Etiology of Precocious Puberty?
Based on the etiology, precocious puberty can be divided into two main groups.
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Central precocious puberty (GnRH dependent).
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Peripheral precocious puberty (GnRH independent).
Central Precocious puberty (CPP):
Due to the HPG axis' early maturation and activity, this kind of precocious puberty constitutes real pubertal development. In girls, the most frequent reason is typically idiopathic, whereas in males, there is typically an underlying pathology. It can be attributed to a wide range of problems. The most pertinent subcategories are:
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CNS Tumors: Hydrocephalus, septo-optic dysplasia, arachnoid cysts, astrocytomas, ependymomas, hypothalamic hamartomas, and pineal tumors.
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CNS Injuries: Injuries to the head, radiation to the head, cerebral palsy, and infections (tuberculous meningitis).
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Genetics: A gain of function mutation the kisspeptin (KISS1) and its receptor (KISSR) genes, and a loss of function mutation in the MRF3 (Makorin ring finger 3) gene.
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Syndromes: Tuberous sclerosis, Sturge Weber syndrome, and neurofibromatosis.
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Environmental: Children adopted internationally, stopping sex steroid therapy.
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Inherited early puberty.
The hypothalamic hamartoma is the most frequent brain lesion that causes CPP. The lesion's ectopic neural cells act as a secondary source of GnRH pulses. Precocious puberty can appear as early as 12 months into infancy. Gelastic seizures, which are typically resistant to treatment, are the most distinctive association. Cognitive, behavioural, and psychiatric problems are some of the additional related characteristics. Children who have been adopted internationally have an increased prevalence. Though the precise process is unknown, theories include a possible function for improved nutrition and exposure to hormone disrupting substances. Familial forms have been reported on a few occasions, although the genetic causes are not fully understood. Kisspeptin (KISS1) and Makorin Ring Finger (MRF3) gene variants and their receptors have been linked to some intriguing correlations in recent years. These genes are in charge of the signals that stimulate and inhibit the release of GnRH. CPP is caused by mutations in these genes that either lose or gain function.
Peripheral Precocious Puberty (PPP):
PPP is the premature development of secondary sexual traits unrelated to the pulsatile release of GnRH, and it results from the generation of sex hormones from either endogenous or exogenous sources. It occurs less frequently than the CPP. Several significant causes include:
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Congenital Adrenal Hyperplasia.
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McCune-Albright Syndrome.
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Gonadal Tumors: Germ cell tumours such dysgerminoma, teratoma, and embryonal tumours, as well as sex cord stromal tumours like Leydig and Sertoli cell tumours.
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Adrenal Tumors.
Rarely, PPP is caused by tumours. Adrenal tumours, and Leydig cell tumours, all produce more androgen than normal. Hepatoblastoma, pineal, and mediastinal tumours all produce more human chorionic gonadotropin (hCG) than other types of tumours.
The clinical phenotype of testitoxicosis, an uncommon autosomal dominant condition, is only present in men. The Leydig cells are activated, and elevated testosterone levels come from a germline activating mutation of the LH receptor gene. Ovarian cysts, primary hypothyroidism, and early puberty are the hallmarks of Van Wyk and Grumbach syndrome. Researchers hypothesise that untreated primary hypothyroidism causes pituitary hyperstimulation, which in turn causes the pituitary to produce various hormones that lead to precocious puberty. A sporadic disorder known as McCune-Albright syndrome is brought on by an activating mutation in the GNAS 1 gene, which codes for the G protein's alpha subunit. This gene activation boosts the production of cAMP, which causes all of its dependent receptors to function excessively. Precocious puberty, fibrous dysplasia of the skeletal system, and café au lait pigmentation are the typical trio of symptoms. Hyperthyroidism, Cushing syndrome, and excess growth hormone are the other endocrine symptoms that are likely to be present.
What Is the Epidemiology of Precocious Puberty?
Studies describing the prevalence and trends of premature puberty are extremely rare. Precocious puberty was estimated to affect 0.2% of females and less than 0.05% of boys in the first epidemiologic study from a Danish national registry. Compared to guys, who made up less than 5 per 10,000 girls, there were roughly 20 to 23 more females than males. The annual incidence of central precocious puberty was estimated by another observational study to be between 0.02 and 1.07 cases per 100,000 people in Spain. According to a study of the Korean population, there are 1.7 cases of CPP for every 100,000 boys and 55.9 cases for every 100,000 girls. Incidence rates for CPP in Koreans were reported to be 15.3 per 100000 females and 0.6 per 100000 boys overall.[4] It is challenging to estimate precise numbers due to the large population-specific variation in frequency and incidence.
What Is the Treatment of Precocious Puberty?
Central Precocious Puberty: Depending on the child's age and the stage of puberty, a treatment selection must be made. Consider treatment if the child's symptoms are intensifying quickly or if their bone age is greatly advanced. Preserving the adult's height and reducing the related psychological stress are the main targets of treatment. The norm of care is GnRH agonists. Both long-acting and short-acting GnRH agonists are available in a wide variety of formulations (intranasal, intramuscular, and subcutaneous). The patient's and the clinician's preferences will determine which formulation is chosen. Leuprolide acetate is the most widely used in the US. Every three months, a depot injection is given.
Peripheral Precocious Puberty: The goal of treatment is to stop the source of sex steroids. Adrenal and gonadal tumours require surgery. Exogenous sources of sex steroids should be eliminated if they are found. With the use of aromatase inhibitors and selective oestrogen selective receptor modulators, there is some efficacy in the treatment of McCune-Albright syndrome. Although the best course of treatment for familial male-limited precocious puberty is not yet known, an androgen antagonist and an aromatase inhibitor are the preferred options.
Conclusion
Precocious puberty, if left untreated, typically results in small stature as well as serious mental and behavioural problems. Precocious puberty puts youngsters at increased risk for high-risk behaviours like substance addiction, behavioural problems, social isolation, absenteeism, and multiple sexual partners, according to a few studies. Additionally, they experience a lot of peer pressure and self-image issues. The majority of these issues are, however, rectified by early adulthood.
