185- What is the role of metformin in premature pubarche?
Girls with premature pubarche due to obesity-mediated hyperinsulinemia have
an increased risk of polycystic ovarian disease (PCOD) and metabolic syn-
drome. Treatment with metformin in girls with premature pubarche has been
shown to prevent the occurrence of early menarche and also reduces the risk of
future development of PCOD and metabolic syndrome. Further, metformin
decreases visceral adipose tissue and increases lean body mass, thereby leading
to improvement in body composition of these adolescents.- What are the causes of premature pubarche with genital ambiguity?
Girls with CAH due to 21α-hydroxylase deficiency, 3β-hydroxysteroid dehydro-
genase type 2 deficiency, and 11β-hydroxylase deficiency present with premature
pubarche and genital ambiguity, while boys with CAH due to 3β-hydroxysteroid
dehydrogenase type 2 deficiency manifest with premature pubarche along with
genital ambiguity. However, boys with 21α-hydroxylase deficiency and 11
β-hydroxylase deficiency have premature pubarche with normal genitalia.- A 3-year-old boy presented with history of brief intermittent staring followed by
uncontrollable laughter and giggling. On evaluation, he had pubic hair tanner
stage 2 and bilateral testicular enlargement of size 6 ml. MR imaging revealed
an extrasellar mass in the hypothalamic region. What is the likely diagnosis?
The most likely diagnosis in the index case is GDPP due to hypothalamic
hamartoma. The unique features of precocious puberty associated with hypo-
thalamic hamartoma include early age of presentation (2–4 years of age),
absence of symptoms of mass effect, and gelastic seizures. Precocious puberty
associated with hypothalamic hamartoma is more common in girls than in
boys, but gelastic seizures are more frequent in boys. In the index case,
appearance of pubic hair at 3 years of age without adrenarche is due to testicu-
lar production of testosterone. In girls, precocious puberty associated with
hypothalamic hamartoma presents as GDPP with progressive and sequential
development of secondary sexual characteristics, but may not have pubarche
in those with onset below 6 years of age. After biochemical confirmation of
GDPP, GnRH agonists are the treatment of choice for patients with hypotha-
lamic hamartoma. - What is hypothalamic hamartoma?
Hypothalamic hamartoma is a bundle of disorganized neuronal tissue compris-
ing of GnRH neurons. It arises due to faulty migration of GnRH neurons from6 Precocious Puberty