Delayed Puberty Etiological Aspects

Actually, after this clinical exam and these simple complementary investigations, the physician often has a presumptive diagnosis. The easiest case is when FSH is elevated (hypergonadotropic hypogonadism). In this case the work-up will be completed with a karyotype. If gonadotropins are low it will be less easy: the physician will have to eliminate organic disease such as a tumor by brain MRI, screen for negative energetic balance, and identify genetic causes of isolated IHH before being able to diagnose an idiopathic constitutive delay of puberty.

Hypergonadotropic Hypogonadism

Elevated FSH and/or LH levels reflect peripheral ovarian disease and raise the need to verify female phenotype, check for the presence of ovarian and uterine tissues by ultrasound, and determine the karyotype on peripheral blood lymphocytes before examining the ovaries by celioscopy and biopsy.

Gonadal Dysgenesis with Chromosomal Abnormalities

Turner's Syndrome and Its Variants
Turner's syndrome, the most frequent cause of primitive ovarian failure, associates in its classical monosomic 45,XO form a female phenotype, short stature, several somatic abnormalities and sexual infantilism. In this form, diagnosis has frequently, but not always, been made during infancy. Any suggestive malformations (webbed neck, nail dysplasia, high palate, short fourth metacarpal and strabismus), growth retardation and/or elevated FSH must lead to the verification of the karyotype. However, in its variant forms with mosaicism or structural abnormalities of an X chromosome (iso, deletion, translocation X/autosome), there are several phenotypes for pubertal development from infantilism to partial development of secondary sex characteristics, primary amenorrhea or even spontaneous puberty. Indeed, spontaneous puberty occurs in 10 - 20%, followed by premature ovarian failure especially in cases of mosaicism with few 45,X cells or deletion of the X short arm.

Treatment with recombinant GH may be able to accelerate partial pubertal development. In fact, both X chromosomes are necessary for the preservation of ovarian function and oocytes. Specifically, some areas such as the Xq13-q26 region contain genes which are thought to prevent premature follicular atresia. In Turner's syndrome, germinal cells are present and normal until the fourth month of intrauterine life. Regression of gonocytes will then depend on the importance of the X defect. At birth, ovarian morphology can vary from ovarian streaks to macroscopically normal ovaries.

Mosaicism can be associated with the partial presence of a Y chromosome found on cytogenetic analysis. A systematic molecular analysis found it in 1 out of 40 cases. If present, castration will prevent the development of gonadoblastoma.