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Disorders of puberty
Whats new ?
Genes associated with autosomal hypogonadotrophic
hypogonadism are being characterized
Cristina Traggiai
Richard Stanhope
morning and then declines during the day. The factors that regulate
the hypothalamopituitarygonadal axis and modulate the timing
of puberty remain unknown, but it is clear that some regulation
is under genetic control.2
Definition
Disorders of pubertal development (Figure 1)
Puberty is defined as the acquisition of secondary sexual characteristics (development of breasts, genitalia and pubic and axillary
hair, and increase in testicular volume) associated with a growth
spurt and resulting in the attainment of reproductive function. It
usually lasts 34 years.1 There is usually a relationship between
the attainment of secondary sexual characteristics and the onset of
growth acceleration at an early stage in girls; in contrast, in boys,
this occurs at genitalia stage 3/4. Although girls enter puberty at
an earlier chronological age than boys, their onset of fertility is
usually later. The first 1 or 2 years after menarche involve anovulatory cycles associated with irregular and often painful periods;
in boys, spermatogenesis begins at Tanner stage 3. When there
are discrepancies (loss of consonance or harmony) between the
timing of different aspects of maturation, an endocrine disorder
should be suspected.
Precocious puberty is defined as development of sexual characteristics before the age of 8 years in girls or 9 years in boys.
Delayed puberty is diagnosed when there is no breast development by 13.4 years of age in a girl or no testicular enlargement by
14 years in a boy.
Endocrinology of puberty
The endocrine events of puberty start many years before the
onset of phenotypic puberty. Luteinizing hormone (LH) secretion
results from both increased secretion of gonadotrophin-releasing
hormone (GnRH) from the hypothalamus and increased pituitary
responsiveness to GnRH. The nocturnal increase in serum LH
is sleep dependent; LH concentration then gradually changes to
the adult pattern of one pulse approximately every 90 minutes
throughout day and night. In girls, peak oestrogen secretion is
during the morning, probably as a consequence of aromatase
induction; in boys, testosterone starts increasing after the first
nocturnal pulse of LH, reaches a peak in the early hours of the
Hypogonadotrophic hypogonadism: it is often difficult to distinguish hypogonadotrophic hypogonadism from constitutional delay
of growth and puberty, particularly in the early teenage years.
However, children with hypogonadotrophic hypogonadism are
taller and grow at a faster rate. Features of Kallmanns syndrome
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Management
Precocious puberty: CPP is treated with a GnRH agonist, which
has the paradoxical action of inducing down-regulation of pituitary
GnRH receptors and desensitization of pituitary gonadotrophs,
with suppression of spontaneous and stimulated pituitary
gonadotrophin secretion. Immediate recovery of the hypothalamopituitarygonadal axis is seen at the end of treatment.12
GIPP is treated with drugs that suppress gonadal steroidogenesis, such as cyproterone acetate, ketoconazole (a steroid
biosynthesis inhibitor), spironolactone (an anti-androgen) and
testolactone (an aromatase inhibitor).12
Delayed puberty is treated for psychological reasons. In boys,
treatment options include depot testosterone (if induction of a
growth spurt and pubertal development is required) and low-dose
anabolic steroid (if virilization is not required). In girls, a course
of oestrogens is required for at least 6 months.13
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