Introduction: LH receptor plays an important role in sexual development and reproductive function. Mutations of this receptor lead to the development of three clinical conditions: Leydig cell hypoplasia, hypergonadotropic hypogonadism with primary amenorrhea and familial male limited precocious puberty. The first two entities result from inactivating mutations. In Leydig cell hypoplasia, with autosomal recessive inheritance, the phenotypic spectrum correlates with the degree of residual activity of mutated receptor.
Case: Thirty six years old patient, referred for evaluation of primary amenorrhea. It presented history of pubarche at 13 years old and absent thelarche (breast development only after esto-progestative therapy), family history of primary amenorrhea in a 1st degree, paternal line, cousin. The examination showed breast development on Tanners stage III, sparse pubic hair, female external genitalia and single, bilateral inguinal masses. Chromosome study revealed to be a 46XY individual. Analytically the patient presented FSH 15.59 mIU/ml, LH 35.71 mIU/ml, prolactin 3.1 ng/ml, estradiol 24.0 pg/ml, total testosterone 0.10 ng/ml and 17-hydroxy-progesterone 0.96 ng/ml. The MRI showed an image suggestive of vagina and in the inguinal regions images suggestive of testicles, ovaries were not identified. Human chorionic gonadotrophin stimulation test was performed with the following results: Testosterone 0.08 (0.08 ng/ml and 17-OH-progesterone 0.94 (0.41 ng/ml. The patient underwent orchiectomy. Histological exam revealed presence of testicular parenchyma devoid of germ cells and absence of Leydig cells. Search for mutations of the LH receptor is ongoing.
Discussion: The more severe forms of Leydig cell hypoplasia are characterized by predominance of female external genitalia and absence of secondary sexual differentiation in puberty. Milder forms have predominantly male external genitalia, micropenis/hypospadias, or infertility without sexual ambiguity. It is biochemically characterized by low testosterone levels, without elevated precursors, even after stimulation with human chorionic gonadotropin, and LH increased levels.