Organic Direct Gonadotropin Deficiency
To establish etiological diagnosis, complete medical history and clinical exam are associated with systematic computed tomography (CT) or magnetic resonance imaging (MRI) scans of the hypothalamic and pituitary areas, as well as assessment of the other pituitary endocrine secretions.

Tumoral Origin
Central nervous tumors leading to delayed puberty can affect either the intra- or extrasellar control of gonadotropins and are usually associated to other anterior or posterior pituitary deficiencies.

-  Craniopharyngioma is the most frequent tumor associated with delayed puberty in girls. It originates from Rathke’s pouch, with generally a suprasellar development around the pituitary stalk. Clinical symptoms of compression (headache or visual disturbances) and/or endocrine deficiencies (asthenia, short stature, diabetes insipidus, infantilism) generally lead to diagnosis between 6 and 15 years of age. Ophthalmological examination finds visual defects such as bilateral temporal field deficit, optic atrophy and papilledema. Full endocrine screening may confirm strong or moderate somatotroph, thyreotroph, corticotroph and vasopressin deficiencies associated to gonadotropin deficiency. Radiographic determination of bone age will verify the presence of bone maturation delay. Supra- and intrasellar calcifications are very much characteristic of such a tumor and are clearly seen on CT scans. Imaging will look for an abnormal sella, a cystic or solid tumor and the presence or absence of hydrocephalus.

Treatment associates transphenoidal microsurgery when possible and radiation therapy. Other endocrine deficiencies are supplemented. It is important for future fertility prognosis to discriminate between a pituitary or suprapituitary origin of the gonadotropin deficiency because of the possibility of administering pulsatile intermittent LHRH in suprahypophyseal defects to induce ovulation and pregnancy.

-  Germinomas or germ cell tumors of the central nervous system (CNS) may cause sexual infantilism with vasopressin and GH deficiency discovered in about the second decade of life. CT and MRI are able to show tumors >0.5cm in diameter. The tumor may be located in the suprasellar hypothalamic region, the pineal region or another area of the CNS. Radiation therapy is the best treatment.

-  Hypothalamic and optic gliomas associated or not to von Recklinghausen disease or astrocytomas seldom cause delayed puberty.

-  Hyperprolactinomas can develop during the peripubertal period and lead to arrested pubertal development with primary amenorrhea. In fact, hyperprolactinemia inhibits pulsatile LHRH secretion, inducing gonadotropin deficiency. Thus, evaluation of the PRL axis is necessary in case of IHH.

-  Irradiation of the head in case of CNS tumors, leukemia or tumors of the head and the face may induce progressive hypothalamo-pituitary deficiency including gonadotropin deficiency.