A 20 yr old woman was referred for primary amenorrhea. At examination BMI was 19 and displayed a pubertal development at S4P4. Hormonal evaluation showed normal prolactin, low estradiol (18 pg/ml) and gonadotropins (LH=1.5IU; FSH=1.9 IU/L). Testosterone was normal (0.25 ng/ml) but curiously plasma progesterone (P) was increased (from 3.9 to 5 ng/ml). Initial ovarian sonography and adrenal CT scan didnt show any abnormal mass. ACTH stimulation tests showed normal responses excluding 21.17 or 11 hydroxylase deficiencies. During these tests circulating P didnt increase and was not suppressed by dexamethasone. Neither GnRH agonist (Dtrp-6, 3 mg IM) stimulated (flare up) nor blunted (desensitization) gonadotropins increased or decreased P levels. Very high P in the right ovarian vein effluent (107 vs 4.9 in the left effluent (ng/ml)) indicate an right ovarian source of P but ovarian sonography remained normal. The LH secretion profile studied during follow up showed 2 LH pulses in 4 hours, a frequency similar to those observed in the luteal phase of normal women. Pulsatile GnRH administration for 21 days (20 μg/90 minutes, sc) failed to increase low E2 levels and to induce the recruitment of a dominant follicle. A 30 mm right ovarian tumour was discovered by ultrasound after 18 month follow up and removed thereafter. Surgical tumour resection was followed by decrease in P levels and appearance of regular menses. Immunohistochemical analysis of the tumour showed expression of P450 scc, 3β-HSD but no expression of P450c 17. To our knowledge, this is the first case of isolated progesterone secretion by an ovarian Leydig cell tumour. This model provide a unique opportunity to evaluate the consequence of a permanent P secretion on the gonatrope axis. Our results indicate that P can exert an inhibitory effect on gonadotropin secretion at both the hypothalamic and pituitary levels.
01 - 05 Apr 2006
European Society of Endocrinology