Tumors of the Hypothalamus and Pituitary Several different tumors of the hypothalamic and pituitary regions may lead to hypogonadotropic hypogonadism (58) (Fig. 29.13A). Except for craniopharyngiomas, these tumors are relatively uncommon in children. A craniopharyngioma is a tumor of the Rathke’s pouch. It is the most common neoplasm associated with delayed puberty, and it accounts for 10% of all childhood central nervous system tumors. Craniopharyngiomas are usually suprasellar in location and may be asymptomatic well into the second decade of life. Such tumors may present as headache, visual disturbances, short stature or growth failure, delayed puberty, or diabetes insipidus. Visual field defects (including bilateral temporal hemianopsia), optic atrophy, or papilledema may be seen on physical examination. Laboratory evaluation should document hypogonadotropism and may reveal hyperprolactinemia as a result of interruption of hypothalamic dopamine inhibition of prolactin release. Radiographically, the tumor may be either cystic or solid and may show areas of calcification. Appropriate therapy for hypothalamic–pituitary tumors may involve surgical excision or radiotherapy (with adequate pituitary hormone replacement therapy) and are best managed by a team of physicians that includes an endocrinologist, a neurosurgeon, and a radiotherapist.
Other Central Nervous System Disorders Other central nervous system disorders that may lead to delayed puberty include infiltrative diseases, such as Langerhans cell-type histiocytosis, particularly the form known previously as Hand-Sch¨uller-Christian disease (Fig. 29.13B and 29.13C). Diabetes insipidus is the most common endocrinopathy (because of infiltration of the supraoptic nucleus in the hypothalamus), but short stature resulting from GH deficiency and delayed puberty caused by gonadotropin deficiency are not uncommon in this disorder (59).
Irradiation of the central nervous system for treatment of any neoplasm or leukemia may result in hypothalamic dysfunction. Although GH deficiency is the most frequent finding, partial or complete gonadotropin deficiency may develop in some patients.
Figure 29.12 Left A 21.-year-old woman with Kallmann syndrome. Note that the patient has some pubic and axillary hair. Bone age was 16 years. It is rare to see affected individuals today who were not given oral contraceptive agents to induce menses (with some consequent breast development). (From Wilkins L. The diagnosis and treatment of endocrine disorders in childhood and adolescence. 3rd ed. Springfield, IL: Charles C Thomas, 1965, with permission.)
Figure 29.13 Right A: A 16-year-old girl with delayed puberty. Breast budding began at 11 years of age, but there was no further development. During the year before presentation, her scholastic performance in school deteriorated, she gained 25 lb, she became increasingly lethargic, and nocturia and polydypsia were noted. Initial evaluation documented low follicle-stimulating hormone, elevated prolactin, and a bone age of 10.5 years. Computed tomography scanning documented a large hypothalamic neoplasm that proved to be an ectopic germinoma. The patient was also documented to be hypothyroid and hypoadrenal and to have diabetes insipidus. Despite the elevated prolactin, she had no galactorrhea because of the minimal breast development. (From Rebar RW. Normal and abnormal sexual differentiation and pubertal development. In: Moore TR, Reiter RC, Rebar RW, et al., eds. Gynecology and obstetrics: a longitudinal approach. New York: Churchill Livingstone, 1993:97–133, with permission.)