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FSH secretion, increased FSH sensitivity due to gain-of-function mutation of
FSH receptor, and increased peripheral sensitivity to estradiol. However, it has
been postulated that isolated premature thelarche may simply be an exaggerated
manifestation of “mini-puberty,” but this is debatable as premature thelarche
does not occur in all girls, and there is a discordance in gonadotropin response
to GnRH (FSH > LH) in girls with isolated premature thelarche.- Why is thelarche nonprogressive in girls with isolated premature thelarche?
The development of breast requires both estrogen and progesterone: estrogen
for ductal and stromal development (B 3 –B 4 ) and progesterone for differentia-
tion of ductal elements into acini (B 5 ). In addition, prolactin, insulin, IGF1, and
LH have a permissive role in breast development. In patients with isolated pre-
mature thelarche, serum estradiol levels are elevated, while serum progesterone
levels are prepubertal; therefore, breast development is restricted up to Tanner
stage B 2 –B 3 only.- What is the difference between adrenarche and pubarche?
Adrenarche is a biochemical event characterized by an increase in adrenal
androgens, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sul-
fate (DHEAS), and usually occurs by 6 years of age. Pubarche is a clinical
event that begins around 8 years of age, and its onset is heralded by the appear-
ance of pubic hair (≤P 3 ), axillary hair, body odor, seborrhea, and acne. DHEA
and DHEAS are weaker adrenal androgens and require conversion to testoster-
one and dihydrotestosterone to mediate their effect on pilosebaceous unit and
consequently pubarche. The conversion of these weaker androgens to testoster-
one occurs in gonads and adipose tissue.- What are the clinical disorders associated with discordance in adrenarche,
pubarche, and gonadarche?
Adrenarche is the consequence of activation of hypothalamo–pituitary–zona
reticularis axis and results in secretion of DHEA and DHEAS. The presence of
gonads is essential for the conversion of weaker androgens DHEA and DHEAS
to testosterone and consequent pubarche. Gonadarche is due to activation of
hypothalamo–pituitary–gonadal axis, thereby resulting in secretion of respec-
tive gonadal steroids. In a normal individual, adrenarche is followed by
pubarche and gonadarche. However, there are many disorders which are associ-
ated with discordance in adrenarche, pubarche, and gonadarche, and these are
summarized in the table given below.
Disorders Adrenarche Pubarche Gonadarche
Premature adrenarche + + −
GDPP (onset <6 years) − May be present in
girls
Present in boys+GDPP (onset >6 years) + + +6 Precocious Puberty