Galactosemia Galactosemia is caused by a lack of functional galactose-1-phosphate uridyl transferase. Galactosemia is a rare cause of POI and is typically diagnosed in childhood prior to presentation with amenorrhea. Galactose metabolites appear to have toxic effects on ovarian follicles, causing their premature destruction (111). Cataracts and mental retardation are associated with galactosemia. There is evidence that heterozygote carriers of this disorder may have suboptimal ovarian function (112). Early dietary modification may delay but not prevent the ovarian failure (26).
Hypothalamic Tumors For normal menstruation to occur, the hypothalamus must be able to secrete GnRH, and the pituitary must be able to respond with production and release of FSH and LH. Tumors of the hypothalamus or pituitary, such as craniopharyngiomas, germinomas, tubercular or sarcoid granulomas, or dermoid cysts, may prevent appropriate hormonal secretion. Patients with these disorders may have neurologic abnormalities, and secretion of other hypothalamic and pituitary hormones may be abnormal. Craniopharyngiomas are the most common tumors. They are located in the suprasellar region and frequently cause headaches and visual changes. The surgical and radiologic treatment of tumors may in itself cause further abnormalities in hormone secretion (Table 30.4).
Pituitary Lesions Hypopituitarism is rare because a large portion of the gland must be destroyed before decreased hormonal secretion affects the patient clinically. The pituitary gland may be destroyed by tumors (nonfunctioning or hormone secreting), infarction, or infiltrating lesions such as lymphocytic hypophysitis, granulomatous lesions, and surgical or radiologic ablations. Sheehan syndrome is associated with postpartum necrosis of the pituitary resulting from a hypotensive episode that, in its severe form (pituitary apoplexy), presents with the patient in shock. The patient may develop a localized, severe, retro-orbital headache or abnormalities in visual fields and visual acuity. Patients with a mild form of postpartum pituitary necrosis cannot lactate, lose pubic and axillary hair, and do not menstruate after delivery.
Diabetic vasculitis and sickle cell anemia rarely manifest as pituitary failure. Hypopituitarism is associated with hyposecretion of ACTH and thyroid-stimulating hormone (TSH) and gonadotropins; therefore, thyroid and adrenal function must be evaluated. If hypopituitarism occurs before puberty, menses and secondary sexual characteristics will not develop.
Growth hormone (GH), TSH, ACTH, and prolactin are secreted by the pituitary, and the excess production of each by pituitary tumors causes menstrual abnormalities. The menstrual abnormalities are caused by adverse effects of these hormones on the GnRH pulse generator and not by direct effects on the ovary. Prolactinomas are the most common hormone-secreting tumors in the pituitary, as described above.
Table 30.4 Pituitary and Hypothalamic Lesions