Pathology of the Endocrine System

THE PITUITARY GLAND This is a small, bean-shaped structure that lies at the base of the brain within the confines of the sella turcica. It is connected to the hypothalamus by a "stalk," composed of axons extending from the hypothalamus. The pituitary is composed of two morphologically and functionally distinct components: the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The adenohypophysis, in H&E stained sections, shows a colorful collection of cells with basophilic, eosinophilic or poorly staining ("chromophobic") cytoplasm. (Fig. 7-1) Immnohistochemistry (and sometimes electron microscopy) is usually employed in typing the hormone (s) present in various pituitary lesions. The release of trophic hormones is under the control of releasing or inhibiting factors produced in the hypothalamus. Hyperpituitarism Causes A. Pituitary; usually anterior lobe 1. Adenoma (the most common cause) 2. Hyperplasia 3. Carcinoma B. Extra-pituitary causes 1. Hormone producing extra-pituitary tumors (ectopic hormone production) 2. Certain hypothalamic disorders Pituitary adenomas are classified according to the hormone(s) produced by the neoplastic cells; these are detected by immunohistochemically-stained tissue sections. Pituitary adenomas can be functional (associated with hormone excess with their related clinical manifestations) or silent. Adenomas are usually composed of a single cell type and produce a single predominant hormone. However, some adenomas can secrete two hormones (e.g. growth hormone and prolactin). Other adenomas are hormone negative. Adenomas are divided on the basis of whether the size is less or exceeds 1 cm. (microadenomas and macroademomas respectively). Macroadenomas can cause hypopituitarism by compressing the adjacent non-neoplastic parenchyma. Pathogenesis Guanine nucleotide-binding protein (G-protein) mutations are the best characterized molecular abnormalities. Such mutations eventuate in a persistent increase in intracellular cAMP, which is a potent mitogenic stimulus promoting cellular proliferation and hormone synthesis and secretion. In the setting of MEN-1 syndrome there are mutations in the MEN-1 (menin) gene. Gross features • Adenomas are usually soft & well-circumscribed • Larger lesions extend superiorly through the sellar diaphragm compressing the optic chiasm and adjacent structures (Fig. 7-2 A). • Invasive adenomas refer to nonencapsulated tumors that infiltrate adjacent bone, dura, and even brain. Microscopic features (Fig. 7-2 B). • Adenomas are composed of monomorphic, polygonal cells displayed in sheets, cords, or papillae. Their nuclei may be uniform or pleomorphic but the mitotic activity is scanty. The cytoplasm of the constituent cells may be acidophilic, basophilic, or chromophobic. • The connective tissue is scanty that is why many lesions are soft & even gelatinous in consistency. The functional status of an adenoma cannot be predicted from its histologic appearance. Pituitary adenomas are responsible for 10% of intracranial neoplasms. High-resolution CT or MRI suggests that 20% of "normal" adult pituitary glands contain an incidental usually silent adenoma measuring 3 mm or more in diameter. The peak incidence of pituitary adenomas is from 30 to 50 years. Prolactinomas are the most common type of hyperfunctioning pituitary adenoma. Hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility. Growth Hormone-Producing Adenomas (somatotroph cell adenomas) are the second most common type of functional pituitary adenoma. Because the clinical manifestations of excessive growth hormone may be subtle,