A 15-year-old boy presents with history of breast enlargement noticed for the past 3 years. It was initially painful for the first 6 months and subsequently, the pain subsided. At this point, he was evaluated by a pediatrician in his annual school health examination, who noticed small testes in addition to gynecomastia. He was then referred to an endocrinologist for further evaluation, where the boy and his parents give the following clinical history. His birth weight was 3 kg. He was born after a term pregnancy by normal vaginal delivery and had a birth weight of 3 kg. Subsequent postnatal history did not include any neonatal seizures or prolonged neonatal jaundice. Subsequent development was age appropriate. He did not experience any episodes of seizures, or prolonged neonatal jaundice. There was no history of any chronic disease, central nervous system trauma, infections or irradiation. There is no history of abdominal or scrotal trauma, surgery or irradiation. He also did not receive any chemotherapy in the past. He does not give any history suggestive of orchitis or other scrotal infections. There is also no history of anosmia. His mother, however, complains of below par scholastic performance with average to poor grades. There is no consanguinity, family history of gyneco-mastia, delayed puberty, anosmia or infertility. Pubertal development was noticed at about 12 years of age. He has one sister who has had normal pubertal development. On examination, the child has a height of 176 cm and weight of 65 kg. Mid-parental height is 166 cm. Arm span is 184 cm and upper to lower segment ratio was 0.83, which is suggestive of eunuchoid proportions. He has sparse facial hair. Axillary (Tanner Stage 2) and pubic hair (Tanner Stage 3) are sparse but present. Stretched penile length is 7.8 cm and bilaterally testes are palpable, small and firm, with a volume of 5 mL. He does not have goiter. His pulse is 74 per minute, blood pressure is 118/60 mm Hg, and respiratory rate is 18. He has a nontender gynecomastia with 5 cm of palpable tissue on the right and 3 cm on the left. His abdomen is soft with no palpable masses and other systems are also normal. No anosmia is appreciated on examination. Biochemical testing reveals normal thyroid, liver and renal functions. Elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 22 mIU/mL (normal 1.4–12) and 53 mIU/mL (normal 0.6–15 mIU/mL) respectively are discovered, with a low testosterone of 14 ng/dL (normal 350–850 ng/dL). A karyotype is ordered, and is 47XXY, which confirms Klinefelter’s syndrome. A detailed evaluation by a psychologist reveals some impulsivity and a normal Intelligence Quotient (IQ).
What are the other causes of gynecomastia?
Medicine
Familial aromatase excess is a disorder caused by overexpression of CYP19A1 gene, leading to an increase in aromatization of adrenal and testicular androgens to estrogens. Affected females can present with premature thelarche and precocious puberty; affected males can present with precocious puberty and gynecomastia, though fertility is usually normal. This is one of the few disorders where aromatase inhibitors cause a marked improvement.
Hyperthyroidism can cause gynecomastia by increasing the SHBG, which causes a decline in the free testosterone levels. Treatment is by control of hyperthyroidism. Primary hypogonadism is a common cause of gynecomastia, caused by low testosterone levels, and low testosterone leading to high LH levels, which activates aromatase, thus further skewing the testosterone to estrogen ratio. Chromosomal disorders like Klinefelter’s, orchitis due to any reason including mumps orchitis, testicular trauma, torsion, surgery chemotherapy or irradiation to testes can result in gynecomastia. Klinefelter syndrome is one of the most common chromosomal disorders in male and classically presents with hypogonadism and gynecomastia (up to two-thirds of all cases of Klinefelter’s). It is also associated with an increased risk of breast cancer in males. Milder variants of disorders of testicular biosynthesis like 17β-hydroxy-steroid dehydrogenase deficiency and minimal androgen insensitivity syndrome can also present with gynecomastia. Secondary hypogonadism due to Kallmann syndrome, combined pituitary hormone deficiency, isolated hypogonadotropic hypogonadism, pituitary trauma, surgery, irradiations, infarcts, tumors or infections can also present with gynecomastia and hypogonadism.
Gynecomastia has also been reported in men with HIV. This can happen due to multiple mechanisms including liver disease, protease inhibitors and nucleoside reverse transcriptase inhibitors, hypogonadotropic hypogonadism, and refeeding mechanism after antiretroviral therapy induced weight gain. The drugs implicated in gynecomastia are numerous and include spironolactone, antiandrogens like finasteride, cancer chemotherapeutic drugs for testicular and prostate carcinoma, ketoconazole, spironolactone, marijuana, flutamide and cimetidine which act by blocking the androgen receptors and inadvertent use of exogenous estrogens.
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