Porth's Essentials of Pathophysiology, 4e

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Disorders of Endocrine Control of Growth and Metabolism

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deficiency) prior to development of headache, visual loss, and other neurologic symptoms due to the mass effect of the expanding tumor. Assessment of Hypothalamic-Pituitary Function The precise assessment of hypothalamic-pituitary func- tion has been made possible by radioimmunoassay of the anterior pituitary hormones and their specific target gland hormones. Magnetic resonance imaging (MRI) is used for imaging the hypothalamus and pituitary. It has largely replaced the use of computed tomography (CT) because it allows better visualization of normal structures and has better resolution in defining tumors. 2 When further information regarding pituitary function is required, combined hypothalamic-pituitary function tests (e.g., rapid ACTH stimulation test or GH suppres- sion test) may be undertaken. 2 The most common cause of hyperpituitarism is a pitu- itary adenoma, or a benign tumor arising from the anterior pituitary. 2–5 Other, less common causes of hyperpituitarism are hyperplasia and carcinoma of the anterior pituitary, secretion of hormones by extra- pituitary tumors, and certain hypothalamic lesions. Clinically diagnosed pituitary adenomas are responsi- ble for about 10% of intracranial neoplasms. They are discovered incidentally in as many as 25% of routine autopsies and are increasingly being detected as inci- dental findings on MRI and CT scans of the head per- formed for other reasons. 6 The usual pituitary adenoma is a well-circumscribed lesion that can range in size from small lesions that do not enlarge the gland (microadenomas, <1 cm) to large, expansive tumors (macroadenomas, >1 cm) that erode the sella turcica and impinge on surrounding cranial structures. 2,5 The adenomas can be divided into non- functional tumors and functional tumors that secrete pituitary hormones. The signs and symptoms of pituitary adenomas include endocrine abnormalities related specifically to functional hormone-secreting adenomas and to the local mass effects of the expanding tumor. Lactotrophic adenomas are the most frequent type of hyperfunction- ing pituitary adenoma, accounting for about 30% of all diagnosed cases. 2,4,5 Lactotrophic adenomas are usually small, benign tumors composed of prolactin-secreting cells. Hyperprolactinemia inhibits the pulsatile secre- tion of LH, which is essential for normal ovulation in women. Thus, the manifestations of hyperprolactinemia are most easily recognized in women of reproductive age and include amenorrhea (lack of menstruation), galactorrhea (spontaneous milk secretion unrelated to pregnancy), and infertility. In males, the symptoms of hyperprolactinemia are vague and may include erectile dysfunction and loss of libido. Pituitary Adenomas and Hyperpituitarism

Because of the close proximity of the sella turcica to the optic nerves and chiasm, expanding pituitary lesions often compress the decussating fibers of the optic chi- asm, giving rise to visual field abnormalities. 2,5 Cranial nerve deficits, which are much less common, can result in blurred or double vision or, very rarely, paresthesia (abnormal nonpainful burning or prickling sensation) on one side of the face. As in the case of any expand- ing intracranial mass, pituitary adenomas may produce signs and symptoms of increased intracranial pressure, including headache, nausea, and vomiting. In some cases, pituitary adenomas may extend beyond the sella turcica into the base of the brain, producing seizures and obstructive hydrocephalus. On occasion, acute hem- orrhage into an adenoma may occur, producing rapid enlargement of the pituitary. The condition, termed pituitary apoplexy , is accompanied by a combination of acute nerve palsies, severe headache, and systemic symp- toms related to ACTH deficiency. Hypopituitarism Hypopituitarism is characterized by a decreased secre- tion of pituitary hormones that causes hypofunc- tion of the secondary organs that depend on trophic stimuli from the pituitary. 1 It may selectively involve one subset of pituitary cells (e.g., somatotropes that produce growth hormone) or all of the pituitary cells, in which case it is referred to as panhypopituitarism . Typically, 70% to 90% of the anterior pituitary must be destroyed before hypopituitarism becomes clini- cally evident. The cause may be congenital, or result from a variety of acquired abnormalities that cause destruction of the anterior pituitary, or from a second- ary phenomenon resulting from a deficiency of hypo- thalamic hormones that normally act on the pituitary. Space-occupying lesions cause hypopituitarism by destroying the pituitary gland or hypothalamic nuclei or by disrupting the hypothalamic-hypophysial portal system. Anterior pituitary hormone loss is usually gradual, especially with progressive loss of pituitary reserve due to tumors or previous pituitary radiation therapy (which may take 10 to 20 years to produce hypopitu- itarism). The loss of pituitary function tends to follow a classic course beginning with the loss of GH, LH, and FSH secretion followed by deficiencies in TSH, then ACTH, and finally prolactin. Impairment of GH secre- tion causes decreased growth in children but may be clinically unapparent in adults. Hypogonadism, mani- fested by amenorrhea in women and decreased libido and erectile function in men, may precede the clinical appearance of other manifestations. The manifestations of hypothyroidism caused by TSH deficiency (e.g., cold intolerance, dry skin, mental dullness) are similar to those observed in primary thyroid failure but less severe. Adrenocorticotropic hormone deficiency is the most serious endocrine deficiency. It causes secondary adre- nal insufficiency, leading to weakness, nausea, anorexia, fever, and postural hypotension.