Sexual development is considered to be precocious if there are any secondary sex characteristics present in girls before age 71/2 years and boys before age 9 years. True 'central' (gonadotropin-dependent) precocious puberty appears to be more common in girls than in boys. In girls, rarely there is underlying CNS disease and it is therefore considered 'idiopathic'. There is a significant incidence of CNS pathology, especially tumours in males with central precocious puberty.
A) PREMATURE THELARCHE -
Refers to frequent finding of isolated breast development in very young girls. Usual age of onset is 12-24 months.
Aetiology -Postulated that premature thelarche is due to small transient bursts of oestrogen from the prepubertal ovary or
from increased sensitivity to low levels of oestrogen in some prepubertal girls. Clinical features - Linear growth acceleration and advanced skeletal maturation are not present.
Breast development does not progress and no other signs of puberty develop.
Gonadotropins and serum oestrogen levels in prepubertal range.
Diagnosis -Non-progressive, benign condition that can be distinguished from true precocious puberty by the normal growth rate and bone age associated with premature thelarche.
B)PREMATURE ADRENARCHE -
Describes the early appearance of sexual hair (i.e. before age of 8 yrs in girls and 9 yrs in boys).
Aetiology - Clinical features -
Diagnosis -Believed to be due to early maturation of adrenal androgen secretion (adrenarche) in some children.
Levels of adrenal androgens are normal for pubertal stage but elevated for chronological age. Bone age may be slightly, but not usually significantly advanced.
Look for other causes of increased androgen production such as congenital adrenal hyperplasia due to 21- hydroxylase, 11-hydroxylase, 3 beta-hydroxysteroid dehydrogenase deficiency or adrenal tumor. In children with significant androgen effect (e.g. advanced bone age, growth acceleration, acne) measurement of adrenal steroids and androgens before and after ACTH will identify those with congenital adrenal hyperplasia.
C)PRECOCIOUS ISOSEXUAL PUBERTY -
I. Gonadotropin-dependent precocious puberty (GDPP) -
May be considered normal puberty beginning at an abnormally early age
Aetiology -GDPP may be idiopathic (as it is in most girls) or secondary to structural and functional disturbances in the CNS
where the onset of puberty originates. A variety of diseases are associated with GDPP, including tumors, hydrocephalus, head injury, congenital malformations and infection.
Clinical features - Progressive development of secondary sex characteristics, beginning in girls before age 7 1/2 yrs and in boys before age 9 yrs accompanied by a growth spurt, causing the child's height to cross isobars on the growth curve. If the GDPP is secondary to another CNS problem, a history of neurologic disease or abnormal neurological findings on physical examination may be present. Because sex steroids stimulate growth while promoting epiphyseal fusion, precocious puberty causes premature closure of the epiphyses and adult short stature. Behaviour problems related to early sexual development and tall stature in childhood are relatively common.
Diagnosis - Based on evidence of growth acceleration, significantly advanced bone age and pubertal levels of gonadotropins and estrogen or testosterone. Because of the episodic secretion of gonadotropins and sex steroids early in GDPP, random daytime measurements may be low. A pubertal pattern of elevated gonadotropins after an intravenous infusion of Gn-RH is indicative of GDPP.
Therapy - Injections of medroxyprogesterone acetate have been used for years to suppress menses and diminish secondary
sex characteristics; though this therapy did not prevent premature epiphyseal fusion and adult short stature. Recently, some long-acting analogues of Gn-RH have been discovered that inhibit gonadotropin release. Clinical trials have been successful in cases of GDPP in decreasing secondary sexual development as well as in slowing growth and skeletal maturation.
2)Gonadotropin-Independent precocious puberty (GIPP) -
Rare cause of precocious sexual development
Examples - Mc Cune-Albright syndrome (polyostotic fibrous dysplasia of bone), some cases of familial precocious puberty in males (testitoxicosis) and Leydig cell tumors and hyperplasia.
Gonadotropin levels are low, and there is no increase in gonadotropins after Gn-RH infusion. GIPP does not respond to treatment with analogues of Gn-RH.
3)Ectopic HCG production -
By neoplasms - may stimulate Leydig cell growth and hyper-secretion of testosterone with the clinical presentation of precocious puberty in males.
Tumors include - hepatoblastoma, pinealoma and retroperitoneal carcinoma.
High LH levels (due to cross reaction with HCG in RIA) and low FSH levels are clue to ectopic HCG production.
Paradoxically it may be associated with sexual precocity.
Growth is arrested in hypothyroidism and bone age is delayed (unlike other cases of precocious puberty). Treatment of hypothyroidism may stop progression of sexual development.