In this scenario, the brain sends a lot of hormonal signals (high gonadotropin), but the gonads are unable to respond to said signals causing hypergonadotropic hypogonadism. Hypergonadotropic hypogonadism can be caused by congenital defects or acquired defects. Congenital disorders
Congenital diseases include untreated cryptorchidism where the testicles fail to descend from the abdomen. Other congenital disorders are genetic in nature. In males, there can be deformities in the seminiferous tubule as in Klinefelter syndrome (most common cause in males), defects in the production of testicular steroids, receptor mutations preventing testicular hormones from working, chromosomal abnormalities such as Noonan syndrome, or problems with the cells making up the testes. Females can also have chromosomal abnormalities such as Turner syndrome (most common cause in girls), XX gonadal dysgenesis, and XY gonadal dysgenesis, problems in the ovarian hormone synthesis pathway such as aromatase deficiency or congenital anatomical deformities such as Müllerian agenesis. Acquired disorders
Acquired diseases include mumps orchitis, Coxsackievirus B infection, irradiation, chemotherapy, or trauma; all problems causing the gonads to fail. Genetic or acquired defect of the hormonal pathway of puberty (hypogonadotropic hypogonadism)
The hypothalamic–pituitary–gonadal axis can also be affected at the level of the brain. The brain does not send its hormonal signals to the gonads (low gonadotropins) causing the gonads to never be activated in the first-place resulting in hypogonadotropic hypogonadism. The HPG axis can be altered in two places, at the hypothalamic or at the pituitary level. CNS disorders such as childhood brain tumors (e.g.
The presence of neurological symptoms in addition to lactation are signs of high prolactin levels and could indicate either a drug side effect or a prolactinoma. Imaging
Since bone maturation is a good indicator of overall physical maturation, an x-ray of the left hand and wrist to assess bone age usually reveals whether the child has reached a stage of physical maturation at which puberty should be occurring. X-ray displaying a bone age <11 years in girls or <13 years in boys (despite a higher chronological age) is most often consistent with constitutional delay of puberty. An MRI of the brain should be considered if neurological symptoms are present in addition to delayed puberty, two findings suspicious for pituitary or hypothalamic tumors. An MRI can also confirm the diagnosis of Kallmann syndrome due to the absence or abnormal development of the olfactory tract. However, in the absence of clear neurological symptoms, an MRI may not be the most cost-effective option. A pelvic ultrasound can detect anatomical abnormalities including undescended testes and müllerian agenesis. Laboratory evaluation
The first step in evaluating children with delayed puberty involves differentiating between the different causes of delayed puberty. Constitutional delay can be evaluated with a thorough history, physical, and bone age. Malnutrition and chronic diseases can be diagnosed through history and disease-specific testing. Screening studies include a complete blood count, an erythrocyte sedimentation rate, and thyroid studies.