The Puberty

The mechanisms initiating puberty are poorly understood but are thought to result from withdrawal of central inhibition of GnRH release. Environmental and physical factors are involved in the timing of puberty (including body fat changes, physical exercise) as well as genetic factors (e.g. a G protein-coupled receptor gene, GPR 54) required for pubertal maturation.

LH and FSH are both low in the prepubertal child. In early puberty, FSH begins to rise first, initially in nocturnal pulses; this is followed by a rise in LH with a subsequent increase in testosterone/oestrogen levels.

In boys, pubertal changes begin at between 10 and 14 years and are complete at between 15 and 17 years. The genitalia develop, testes enlarge and the area of pubic hair increases. Peak height velocity is reached between ages 12 and 17 years during stage 4 of testicular development. Full spermatogenesis occurs comparatively late.

In girls, events start a year earlier. Breast bud enlargement begins at ages 9-13 years and continues to 12-18 years. Pubic hair growth commences at ages 9-14 years and is completed at 12-16 years. Menarche occurs relatively late (age 11-15 years) but peak height velocity is reached earlier (at age 10-13 years), and growth is completed much earlier than in boys.

Precocious puberty

Development of secondary sexual characteristics, or menarche in girls, at or before the age of 9 years is premature. All cases require specialist assessment by a paediatric endocrinologist.

Idiopathic (true) precocity is most common in girls and very rare in boys. This is a diagnosis of exclusion. With no apparent cause for premature breast or pubic hair development, and an early growth spurt, it may be normal and may run in families. Treatment with long-acting GnRH analogues (given by nasal spray, by subcutaneous injection or by implant) causes suppression of gonadotrophin release via downregulation of the receptor - and therefore reduced sex hormone production - and is moderately effective; cyproterone acetate, an antiandrogen with progestational activity, may also be used.

The following are other forms of precocity:
Cerebral precocity. Many causes of hypothalamic disease, especially tumours, may present in this way. In boys this must be rigorously excluded. MRI scan is almost always indicated to exclude this diagnosis.
McCune-Albright syndrome. This is usually in girls, with precocity, polyostotic fibrous dysplasia and skin pigmentation (cafe-au-lait). An activating mutation of the GNAS1 gene encoding the α-subunit of Gs protein has been found.
Premature thelarche. This is early breast development alone, usually transient, at age 2-4 years. It may regress or persist until puberty. There is no evidence of follicular development.
Premature adrenarche. This is early development of pubic hair without significant other changes, usually after age 5 years and more commonly in girls.

Delayed puberty

Over 95% of children show signs of pubertal development by age 14 years. In its absence, investigation should begin by age 15 years. Causes of hypogonadism (see below) are clearly relevant but most cases represent constitutional delay.

In constitutional delay, pubertal development, bone age and stature are in parallel. A family history may confirm that other family members experienced the same delayed development, which is common in boys but very rare in girls.

In boys, a testicular volume > 5 mL indicates the onset of puberty. A rising serum testosterone is an earlier clue.

In girls, the breast bud is the first sign. Ultrasound allows accurate assessment of ovarian and uterine development.

Basal LH/FSH levels may identify the site of a defect, and GnRH (LHRH) tests can indicate the stage of early puberty.

If any progression into puberty is evident clinically, investigations are not required. When delay is great and problems are serious (e.g. severe teasing at school), low-dose short-term sex hormone therapy is used. Specialist assessment is advisable.