Endocrine Abstracts

A 29-year-old male presented with primary infertility, with no identifiable wife factor. He had premature puberty and a family history of infertility (sister). He maintained normal libido and erectile function, with regular sexual activity. He noted progressive testicular enlargement. Physical examination revealed normal vital signs and secondary sexual characteristics, with a BMI of 30. No gynecomastia or Cushingoid features were observed. Testicular assessment showed bilaterally enlarged, firm testes with mildly tender bilateral palpable masses. Initial hormonal evaluation demonstrated undetectable FSH and LH, elevated total testosterone 51 nmol/l (N 8.33- 30.30.1 nmol/l), and increased estradiol (275 pmol/l, (N.40-162 pmol/l), ACTH was 42.8 pg/mL (N, 4.7 to 48.8 pg/mL), Semen analysis confirmed azoospermia.

Differential diagnoses included

• exogenous testosterone or anabolic steroid use,

• testosterone-secreting tumors,

• congenital adrenal hyperplasia (CAH),

• androgen resistance syndromes.

Required Work up

Total testosterone.

LH & FSH.

androstenedione.

17-OH progesterone.

Morning Cortisol

US scrotum

CT adrenal

Further hormonal workup revealed:

• Elevated 17-hydroxyprogesterone 615 nmol/l (N 1.12- 7.0 nmol) and androstenedione >35 nmol/l (N. 2.1-10.0 nmol/l).

• Persistently undetectable LH and FSH

• Low morning cortisol 40 nmol/l (N.200 – 650 nmol/l)

• Elevated aldosterone1010 pmol/l (N. 128-650 pmol/l) and renin levels >35 nmol/l (N. 2-10 nmol/l)

• normal HbA1 c 5.1% (4-5.9%)

Imaging studies:

• Testicular ultrasound showed bilateral enlargement with heterogeneous echotexture and echogenic masses predominantly in the rete testis, suggestive of testicular adrenal rest tumors (TART).

• CT imaging revealed mild bilateral adrenal enlargement without discrete lesions.

Diagnosis: Congenital adrenal hyperplasia.

Treatment initiated: Hydrocortisone (20/20/5) and nighttime dexamethasone (1 mg).

Follow-up at three months showed minimal biochemical improvement despite good compliance by the patient. Testosterone remained elevated >35 nmol/l (N. 8.33-30 nmol/l), minimal reduction of 17-OH progesterone 510.40 nmol/l (N 1.12-7.2 nmol/l) and androstenedione levels persisted above normal > 35 nmol/l (N 2.1-10.8 nmol/l), Aldosterone reduced by 50% to normal 550 pmol/l (N.128-650 pmol/l), and azoospermia continued. Testicular findings remained unchanged.

Follow-up at six months showed worsening of 17 OH progesterone to 660 nmol/l (N. 2-7 nmol/l), Testosterone remain elevated > 35 nmol/l (N 8-30 nmol/l) as well Androstenedione >35 nmol/l (N. 2.1-10.0 nmol/l).possible steroid side effect as worsening HbA1 c to 6.1(N 4-5.9%).and patient complaint of weight gain. Discussion Points:

• What explains the elevation of renin and aldosterone?

• Why is there inadequate suppression of 17-OH progesterone and androstenedione?

• Could 11β-hydroxylase deficiency be contributing?

• Would genetic testing alter management?

• Is there a role for adrenalectomy?

• Should we measure blood Dexamethasone level, to confirm compliance

•  Shall we involve urology for microscopic testicular sperm extraction (microTESES).