The Journal of the Arkansas Medical Society Issue 3 Vol 115 | Page 16

A thorough physical examination
and family history can guide
the provider in formulating a
diagnostic plan that might avoid
unnecessary testing.
development before eight years of age in girls
and nine years of age in boys. The most common
form of PP is central precocious puberty caused
by various causes that lead to early activation
of the hypothalamic-pituitary-gonadal axis. It is
characterized by elevated gonadotropins (LH and
FSH). Peripheral or gonadotropin-independent PP,
on the other hand, causes iso- or contra-sexual
precocity due to the increased levels of sex ste-
roids (testosterone or estrogen) in the absence
of FSH and LH elevation. Excess sex steroids in
peripheral precocious puberty (PPP) can be due
to endogenous sources, such as the gonads or
adrenal glands, or from exogenous sources like
topical products.
Figure 1. Patient’s growth chart. Note markedly advanced bone age (arrow) which
compromises adult height prediction.
(23 ng/dl; RR<16) levels. LH and FSH concen-
trations were within the pre-pubertal range. He
had normal beta-hCG (<2.35 mIU/ml), 17-OHP
(23 ng/dl), and DHEA (50 ng/dl, RR<65) levels.
Pelvic and scrotal US showed no mass or lesion
that could potentially be responsible for exces-
sive androgen production.
The patient’s father had been on topical tes-
tosterone replacement for the past five years for
a diagnosis of hypogonadism of unknown etiol-
ogy. His 6-year-old sister was diagnosed with
premature adrenarche by her primary care phy-
sician when she presented with pubic hair and
was found to have advanced bone maturation of
8 years (>2 SD above the mean). The patient’s
mother has inflammatory acne and has been
treated with spironolactone (anti-androgen) for
the last two years.
Given the negative initial work-up, our patient
was diagnosed with possible exogenous testos-
terone exposure. We asked the patient’s father to
discontinue topical therapy. After one month, the
patient’s testosterone level dropped to 29 ng/
dl, and at six months, to 9 ng/dl (RR<10). His
growth velocity was 4.5 cm/year (normal 4-6 cm/
year), and a repeat bone age showed no further
advancement. However, there was no noticeable
change in his penile size.
Discussion
Precocious puberty (PP) refers to the onset
of physical and hormonal changes of pubertal
64 • THE JOURNAL OF THE ARKANSAS MEDICAL SOCIETY
Sustained secondary exposure to exogenous
testosterone is a well-characterized etiology of
sexual precocity in boys and virilization in girls.
We described a 3-year-old boy with increased
penile size, pubic hair, and significantly advanced
bone age. Due to the fact that the patient had
been exposed to topical testosterone since birth,
he likely had been experiencing accelerated linear
growth from infancy. As a result, neither the family
nor the referring provider recognized his signifi-
cant growth spurt or examined the patient’s bone
age. By the time of referral, the patient’s bone age
was five years advanced with an adult height pre-
diction markedly below his genetic height poten-
tial (Predicted adult height 151 cm; Mid-parental
target height 178 cm). Additionally, evidence of
secondary exposure was also present in other
family members. The patient’s 6-year-old sister
had an advanced bone age and presence of pubic
hair. Their mother had been receiving spironolac-
tone, an androgen-blocker, for inflammatory acne.
Signs and symptoms of all family members were
presumably attributed to inadvertent exposure to
the father’s topical testosterone. This assumption
was confirmed after the cessation of topical tes-
tosterone treatment, which improved the patient’s
serum testosterone levels after one month.
In previously reported cases of precocious
puberty due to exogenous exposure, symptoms
resolved after discontinued exposure. Martinez-
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