249- What is the cause of pubertal gynecomastia?
During puberty, the level of serum estradiol increases by threefold, whereas
serum testosterone increases by more than 30-fold. Therefore, the adult levels
of serum estradiol are achieved earlier as compared to adult levels of serum
testosterone, thereby leading to altered testosterone/estradiol ratio and conse-
quent gynecomastia. The early rise in serum estradiol is due to LH-mediated
increase in testicular aromatase activity as well as increased aromatase expres-
sion in adipose tissue during peripubertal period. Other possible mechanisms
for pubertal gynecomastia include increased sensitivity to estradiol, peripuber-
tal spurt in IGF-1 secretion, leptin and estrogen receptor polymorphisms, and
increased CAG repeats in androgen receptor.- When to evaluate a patient with gynecomastia?
Gynecomastia (subareolar disk diameter) >5 cm in obese and >2 cm in lean
subjects merits evaluation. However, all patients with recent onset, rapid or
painful gynecomastia should also be evaluated, irrespective of size. In addition,
patients with unilateral gynecomastia or suspicion of malignancy should also
undergo further workup.- What are the biochemical investigations required in a patient with
gynecomastia?
Once a decision to evaluate the patient has been made, renal and liver function
tests should be obtained. If these are normal, then estimation of LH, FSH, tes-
tosterone, prolactin, and thyroid function test should be carried out. In those
with rapidly progressive gynecomastia, estimation of serum β-hCG and estra-
diol level should be done. Further, those patients with suppressed LH and
increased testosterone also merit evaluation for hCG-secreting tumors. Elevated
levels of serum β-hCG point to a diagnosis of hCG-secreting germ cell tumors,
whereas markedly increased serum estradiol levels suggest the possibility of
Leydig/Sertoli cell tumor and rarely, adrenocortical carcinoma. - A 16-year-old boy presented with gynecomastia and was diagnosed to have
Klinefelter’s syndrome. He presented after 3 years with history of rapid enlarge-
ment of breast. He was not on testosterone replacement. What is the likely
cause?
Gynecomastia is common in patients with Klinefelter’s syndrome (38–75 %),
and initiation of testosterone therapy can result in appearance/worsening of
gynecomastia in these patients. However, the index patient had rapid progres-
sion of gynecomastia without testosterone replacement therapy. This should
raise a suspicion of hCG secreting germ cell tumor, which is 500-fold more
common in patients with KFS, as compared to the general population. The most
common site of hCG secreting germ cell tumor in patients with KFS is medias-
tinum, followed by pineal gland and testes. Hence, serum hCG level should be
estimated in this patient.
7 Delayed Puberty