The main function of puberty is to produce sexually mature adults. The hormonal changes of puberty allow children to become reproductively viable. Puberty is also a period of increased linear growth; a large portion of an individual’s height is achieved from the growth occurring in puberty.

The mechanism of the initiation of puberty is not entirely understood; however, it is known that the GnRH neurons are the primary role player in the initiation of puberty. The GnRH neurons develop in the olfactory placode and then migrate to the area of the hypothalamus during the gestational period. Puberty begins with the pulsatile secretion of GnRH from these neurons, other neurotransmitters, GABA and NMDA, are also linked with this process. Additionally, the genes KISS1 and neurokinin B have recently been shown to be involved in the regulation of GnRH release. The increased levels of GnRH increase the release of LH and FSH from the anterior pituitary. During puberty, the negative feedback mechanism is less sensitive allowing for higher levels of FSH and LH to circulate within the body. FSH increases estrogen production by the ovaries in girls, and in boys triggers testicular growth and supports maturing spermatozoa. LH initiates ovulation and creates the corpus luteum in females, and in males acts on Leydig cells in the testes to increase testosterone production. The Increased production of adrenal androgens leading to the development of acne, axillary hair, body odor, and pubic hair is also taking place during the onset of puberty. The linear growth seen in puberty is a result of pulsatile increases in growth hormone (GH) secretion, which is secreted by the pituitary gland. Increases in insulin-like growth factor 1 are also present. Estrogen increases the rates of GH secretion and is involved in growth plate acceleration and fusion. Testosterone increases insulin-like growth factor 1 levels and bursts of GH secretion.[3]

The first-line assessment for any child experiencing issues with pubertal development is a thorough history and physical exam. The history will allow the healthcare practitioner to gain insight as to if there is any possibility of a genetic cause. The history will also provide vital information about the child’s growth pattern and development to date. In addition, it may also point out clues to other causes of pubertal disorders such as poor nutrition, underlying disease, excessive exercise, or the use of exogenous steroids. The physical exam should include an examination of the genitalia and the breasts in girls to determine tanner staging. Tanner staging is a standard system used to categorize the different stages of pubertal development a child has achieved. For boys, Tanner staging includes testes and penile growth, pubic hair distribution, and linear growth. In girls, Tanner staging includes breast development, pubic hair distribution, and linear growth. In addition to tanner categorizations examination of the optic fundus and determining if the sense of smell is intact can be helpful. Standardized growth charts tracking the child’s growth over time are also helpful in determining if a child is developing appropriately.[4] Skin lesions noted on the physical exam can also point toward certain causes of abnormal puberty such as McCune-Albright Syndrome. An x-ray of the left wrist is commonly used to determine bone age and whether the child’s bone maturation is more advanced than their age, suggesting they might be going through premature puberty. In addition to an x-ray of the left wrist, central nervous system (CNS) imaging may be performed if there are signs of CNS involvement. Measurement of hormone levels may also be helpful in the presence of abnormal puberty. Levels of estradiol, testosterone, FSH, and LH can be measured looking for pubertal or prepubertal levels. A GnRH stimulation test is also helpful to determine a central or peripheral cause. The test involves the administration of 100 micrograms of GnRH after overnight fasting and observing the levels of FSH, LH, estradiol, and testosterone at 15, 30, 45, and 60 minutes post-injection. The stimulation test will cause activation of the hypothalamic-pituitary-gonadal axis in central causes resulting in increased levels of the hormones, a peripheral cause will not increase hormone levels.[2] Additional testing that may be done includes, thyroid hormone levels (TSH, T3, T4), blood glucose levels, a complete blood count, liver enzymes, and an erythrocyte sedimentation rate. Another type of testing that can be done is a karyotype which will show the child’s chromosomal pattern and is helpful if there is a suspicion of Turner or Klinefelter’s syndrome. Although there are many other factors that could be evaluated after a history and physical the testing should be tailored individually for each child’s presentation and towards the most likely cause of their abnormal puberty.

The pathophysiology of puberty can be broken down into 3 main categories premature puberty, delayed puberty, and contrasexual development.

Premature Puberty

Precocious puberty or early development of secondary sexual characteristics is defined as pubertal development before age 6 in African American girls and before 7 years in all other girls; however, an age of anything younger than 8 years is also used. Precocious puberty is defined in boys as the development of secondary sexual characteristics before age nine. Many of the causes of early pubertal development are shared however there are some causes of early puberty unique to each of the sexes.[5]

The causes of precocious puberty shared by either gender include benign premature adrenarche, central nervous system and pituitary lesions, constitutional and idiopathic precocious puberty, McCune-Albright syndrome, and exogenous sex hormones.

• Premature adrenarche correlates with the premature presence of pubic or axillary hair and possibly increased sebaceous gland activity without other signs of puberty present, usually before 6 years of age. This is usually an isolated abnormality, and most children go on to develop the other signs of puberty at a normal age. Plasma DHEAS is usually elevated to pubertal levels. Other sex hormones such as FSH, LH, estradiol, and testosterone are typically at levels found in children before puberty. Other studies such as a GnRH stimulation test will show prepubertal results, and an ACTH stimulation test may be used to exclude congenital adrenal hyperplasia which can have similar presenting symptoms.[2]

• CNS and pituitary lesions will typically present with normal stages of puberty but occurring prematurely. Children may have a bone age greater than their chronological age. Additionally, these lesions may come with other problems such as visual field defects. If a central nervous system lesion or a pituitary lesion is suspected, an MRI of the brain can determine the presence of a lesion in these areas.

• Constitutional/idiopathic precocious puberty tend to present more often in females but can occur in both boys and girls. Precocious or premature puberty is considered idiopathic when a child has no familial links to premature development and there is no other cause that can be found for the premature development of puberty. Constitutional precocious puberty can be linked to a familial tendency toward early development. Children with these disorders will respond to a GnRH stimulation test with pubertal levels of sex hormones as well as FSH and LH. These children may have a bone age that is much higher than their chronological age. Additionally, all other causes of premature puberty must be ruled out such as CNS pathology and elevated adrenal hormones.[2]

• McCune-Albright syndrome is associated with cafe-au-lait spots, polyostotic fibrous dysplasia, and precocious puberty. McCune-Albright syndrome is also associated with other endocrine disorders. The cafe-au-lait spots can be large and have been described as resembling the coast of Maine.

• Exogenous sex hormones in substances such as oral contraceptives and anabolic steroids can cause secondary sexual characteristics to develop. These causes can usually be ruled in or out as a cause rather quickly by running a urinalysis. The metabolites of exogenous hormones can be found in the urine. Additionally, children who have an exogenous hormone source and are not undergoing natural puberty will lack pubic hair. Girls may have darkened areolae, and boys will have small testicles of a prepubertal child.[2]

Causes of premature puberty unique to males include gonadotropin secreting tumors, benign gynecomastia of adolescence, and familial gynecomastia.

• Gonadotropin secreting tumors are tumors that typically secrete hCG like components that can have a similar function in signaling to LH resulting in an incomplete type of premature puberty in boys. Girls, however, need FSH to increase estrogen production in the ovaries and thus, will not have premature development due to this type of tumor alone. Examples of tumors that might produce hCG are hepatomas, teratomas, and germinomas of the pineal gland.[2]
• Benign gynecomastia of adolescence is gynecomastia in boys in mid to late puberty is very common. The breasts will often be tender. If the history and physical examination fall within normal limits reassurance and monitoring is all that is necessary, the gynecomastia will usually resolve on its own.[2]
• Familial gynecomastia appears during puberty and has a genetic link usually either x-linked recessive or sex-linked dominant. Some boys may need cosmetic surgery; however, most will not require further evaluation unless there is a suspicion of hypogonadism.[2]

The causes of the signs of premature puberty unique to females include premature menarche, and premature thelarche.

• Menarche typically occurs two-and-a-half years after breast development begins with an average age of first menses being 12.5, any menses occurring before the onset of breast development, without any other signs of puberty, or in a child under the age of 8 is concerning for premature menarche.[4] Premature menarche is not entirely understood; however, it is thought to be due to transient activity by the ovaries. Premature menarche can also be the result of exogenous estrogens. Girls with premature menarche are usually just monitored frequently to ensure there are no signs of underlying pathology.
• Premature thelarche is the development of breast tissue in either or both breasts without other signs of puberty present or before 8 years of age.[2] The breast tissue does not form that of a mature breast. DHEAS is elevated to stage 2 pubertal levels. Premature thelarche usually can be left to resolve on its own, and biopsying this tissue is not recommended it could completely alter the tissue and its future development if done.

Delayed Puberty

Delayed puberty is the lack of physical evidence of puberty by 2 to 2.5 standard deviations above the mean age for the initiation of puberty. In boys, this is considered a period longer than four years between the first signs of testicular enlargement and the end of puberty, or the absence of testicular growth by 14 years old. Delayed puberty in girls is considered the absence of breast growth by 13 years old or more than four years between thelarche and menarche. The causes of delayed puberty include hypogonadotropic hypogonadism, hypopituitarism, constitutional delay, chromosomal abnormalities, and hypothalamic dysfunction due to secondary causes.[6]

• Hypergonadotropic hypogonadism is the failure of the gonads to produce sex hormones. FSH and LH will be elevated because there is no negative feedback on the hypothalamic-pituitary-gonadal axis. There can be many causes of gonadal failure including genetics and physical trauma. In boys, Noonan syndrome and myotonic dystrophy have been known to cause gonadal failure. Additionally, there have been cases of LH beta receptor mutations reported in boys resulting in a lack of a gonadal response. Trauma to the testes by testicular torsion or cryptorchidism is also a cause of gonadal failure in boys. In females, autoimmune ovarian failure is a possible cause, and the child will likely have signs or symptoms of other autoimmune conditions. Interestingly, half of the girls with galactosemia have been shown to develop ovarian failure probably due to toxic metabolites.[6]
• Hypopituitarism is a lack of release of hormones from the pituitary gland. Delayed puberty is not the only sign of hypopituitarism other endocrine dysfunctions such as hypothyroidism, bone growth, and adrenal insufficiency may also be present. Kallmann syndrome is a specific disorder falling under hypopituitarism where neurons in the developing brain fail to migrate resulting in the absence of a sense of smell or anosmia and a lack of gonadotropin-releasing hormone cells in the hypothalamus.[4]
• Constitutional delay of puberty happens to children who have had normal development up until that point. These children then begin to fall to the bottom of the growth curve, and their growth significantly slows down. These children will have prepubertal levels of FSH, LH, estradiol, and testosterone on a GnRH stimulation test. Eventually, puberty will spontaneously occur resulting in the progression of development in these children. [6]
• Chromosomal abnormalities are a cause of delayed puberty shared by both males and females however different abnormalities are found as the cause in each sex. For girls, Turner syndrome is a common cause of ovarian failure where there is a problem with one of the X chromosomes. These girls will often be 45 X or 45 X/46 XX. Along with ovarian failure, Turner syndrome has a great deal of other identifying characteristics including but not limited to a webbed neck, short stature or delayed growth, coarctation of the aorta, a shield chest, and widely spaced nipples. Although there are many possible physical signs of Turner syndrome, sometimes these females are not identified until there is an absence of menses or a fertility problem. This is because some of these girls with Turner syndrome will show the development of pubic hair and breast development. For boys, one of the most common disorders is Klinefelter syndrome, which can have a multitude of chromosomal patterns including 48, XXXY, 48, XXYY, and 49 XXXYY. Klinefelter syndrome typically presents with small testes, gynecomastia, tall stature, and with long legs and short arms. This disorder will cause puberty to not come to completion rather than a complete delay.[4]
• In addition to the above causes of delayed puberty pubertal delay can also be seen in multiple different illnesses where hypothalamic dysfunction can occur. Some examples are hypothyroidism, cystic fibrosis, sickle cell disease, celiac disease, and diabetes mellitus to name a few.[6] Additionally, poor nutrition and the use of long-term glucocorticoids has been linked to delayed puberty.

Contrasexual Development

Contrasexual development occurs when male or female children develop physical features of the opposite gender. This condition tends to be more common in girls and is commonly caused by polycystic ovaries and increased responses by the adrenal gland. Girls will have a male like distribution of hair and may develop hirsutism. Girls can also develop clitoromegaly and lose contour of the breast mass. The possible causes include Cushing syndrome, acromegaly, exogenous androgens, adrenal tumor, ovarian tumor, and hyperprolactinemia. Although contrasexual development is less common in boys, the cause is typically estrogen-secreting tumors.[2]

Puberty is an extremely significant process and a part of all children’s development into functional adults. During this time children begin to gain the capacity for reproduction, which is essential to discuss with children as they progress through puberty. Discussion of sexual practices is an important aspect of well-child visits and is pertinent to identify children that may be having unsafe or high-risk sexual encounters. The discussion of the sexuality by pediatricians or other medical caregivers with young teens as they progress into adulthood provides a chance for them to speak to someone under confidentiality and ask specific questions to understand better their sexuality as well as what is considered safe sexual practices.[7] Puberty also coincides with a child’s psychosocial development. Children who may be early or behind in attaining the milestones of puberty in comparison to their peers are at a much higher risk of emotional distress and low self-esteem. The ability to monitor the progression of puberty in the pediatric population is vital as it is essential to their reproductive development but also because of the many physical and psychological risks children face during this time in their development.