As nonfunctioning pituitary tumors grow, they compress the pituitary gland, pituitary stalk, and hypothalamus and interfere with normal pituitary hormone production. This can lead to partial or complete anterior pituitary hormone deficiency (11).
The first hormone to become deficient is usually GH. Therefore, children with growing masses in the pituitary region usually have growth failure. Adults with GH deficiency do not have specific symptoms, although GH deficiency does have some nonspecific effects on energy and sense of well-being in adults (see Chapter 12).
The next hormones to become deficient are usually the gonadotropins. Prepubertal children have no effects from gonadotropin deficiency, but adults develop oligoamenorrhea, impotence, and/or infertility. Deficiencies of TSH, which leads to hypothyroidism, and ACTH, which leads to hypoadrenalism, are less common, even with large tumors. Deficiency of prolactin (PRL) is also uncommon and only presents in the postpartum period as a failure to lactate. Diabetes insipi-
dus as a result of deficiency of the posterior pituitary hormone vasopressin (antidiuretic hormone [ADH]) is much less common, even with very large pituitary adenomas. The presence of diabetes insipidus should raise the suspicion that the lesion is not a pituitary adenoma.
The clinical presentation of a patient with hypopituitarism is nonspecific and thus may lead to confusion. Many of the symptoms of hypopituitarism are vague, and patients can be misdiagnosed with chronic fatigue or psychiatric illness before the true diagnosis is known. In addition, symptoms of one hormone deficiency may mask those of another hormone deficiency. For example, weight gain is expected with hypothyroidism and weight loss with hypoadrenalism. If a patient has both TSH and ACTH deficiencies, weight may be increased, decreased, or unchanged from baseline.
Finally, routine screening for individual hormones may not uncover pituitary hormone deficiency. For example, the recommended screening test for hypothyroidism is a TSH level, which is highly sensitive for primary hypothyroidism but useless in hypopituitarism. Patients with central hypothyroidism caused by a pituitary tumor may have low, normal, or even mildly elevated TSH levels. To diagnose central, rather than primary, hypothyroidism, a free T4 level must be interpreted in conjunction with suggestive symptoms.
One pituitary hormone that can be nonspecifically elevated by nonfunc-tioning tumors is PRL. It is not unusual to see mild to moderate hyper-prolactinemia (up to 200 ^g/dL or 4,000 mU/L) in patients with large nonfunctioning pituitary tumors or other pituitary-hypothalamic diseases. The source of the PRL is not the tumor, but normal lactotrophs that produce excess PRL when there is an interruption of hypothalamic input of dopamine, the PRL inhibitory factor. This can cause confusion or misdiagnosis if the tumor is mistakenly believed to be a prolactinoma. Prolactinomas are almost always treated medically with dopamine agonists, which are highly effective in lowering PRL levels, resolving symptoms, and reducing tumor size in prolac-tinoma patients (see Chapter 2).
Dopamine agonists will also lower PRL levels in patients with nonfunctioning tumors but do not treat the tumor mass itself. In that case, the tumor may continue to grow while the patient and care provider are falsely reassured by the lower PRL levels and sometimes even a return of a normal menstrual cycle. For this reason, PRL levels must be interpreted cautiously in patients with large tumors, and mild elevations in patients with large tumors are most consistent with a nonspecific PRL elevation, rather than a prolactinoma.
It should be noted that the symptoms listed for nonfunctioning pituitary adenomas are nonspecific. Any large mass or infiltrative process in the pituitary/ hypothalamic region can produce identical symptoms of mass effect and/or hypopituitarism. Therefore, the differential diagnosis of these lesions includes craniopharyngiomas, meningiomas, gliomas, metastatic tumors, and other tumorous or infiltrative processes. In some cases, magnetic resonance imaging (MRI) characteristics or elevated serum gonadotropin levels can help with the differential diagnosis, but pathologic examination of tumor tissue may be needed for the final diagnosis.
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