Pituitary Hyperplasia.

From Lewis S. Blevins Jr., MD  –  Hyperplasia is an increase in the number of cells in a tissue. The cells are related, in that they may be of the same cell type, but are not derived from the same parent cell. A tumor is an increased number of cells in a tissue that are all derived from a single cell that has undergone change that leads to uncontrolled cell division. All of the cells are derived from an related to that single parent cell.

Hyperplasia usually, but not always, has an underlying cause. However, some cases remain poorly understood and yet do seem to be related to genetic conditions or some other abnormality in the cell cycle in affected tissues.

Hyperplasia can occur in almost every single tissue of the body.

Hyperplasia indeed does affect the pituitary gland. Almost any cell type can be affected. For example, some patients have hyperprolactinemia due to hyperplasia of the lactotroph, or prolactin producing cells, of the pituitary gland. The most common cause of this disorder is pregnancy. Estrogens produced by the placenta stimulate the pituitary gland to nearly double in size. Most of that increase in size is related to hyperplasia of the prolactin producing cells. Physiologically, this readies the pregnant woman to breast-feed her child. Birth control pills are another common cause of hyperplasia of the prolactin producing cells. Other patients have unexplained hyperplasia and hyperprolactinemia.

Another group of hyperplasia’s occurs in patients who have longstanding untreated or poorly treated pituitary target gland hormone deficiencies. For example, after menopause, or in women who have had a hysterectomy and ovariectomy at an early age, lack of estrogen’s results in hyperplasia of the LH and FSH producing cells of the pituitary gland. The same is often seen in men with Klinefelter syndrome and primary hypogonadism due to other causes. Hyperplasia, with development of profound hyperpigmentation of the skin, can be seen in patients with long-standing Addison’s disease leading to hyperplasia of the ACTH producing cells. Importantly, patients with long-standing primary hypothyroidism may develop hyperplasia of the TSH producing cells of the pituitary gland. Prolactin levels are often elevated and some patients are suspected of having prolactinoma because of the hyperprolactinemia and enlargement of the pituitary gland.

Hyperplasia may be associated with other hormone hypersecretory states. For example, it has been reported that as many as 4% of patients with Cushing’s disease might actually have an ectopic CRH producing tumor that stimulates the ACTH cells of the pituitary gland to become hyperplastic, secrete ACTH, and cause hypercortisolism. Growth hormone-releasing hormone neuroendocrine tumors, most commonly in the pancreas, stimulate the growth hormone cells of the pituitary gland to become hyperplastic leading to the clinical syndrome of acromegaly. Hypothalamic tumors known as hamartomas may secrete hypothalamic hormones that stimulate the pituitary and can cause pituitary hyperplasia and lead to precocious puberty, acromegaly, and giantism in children.

One other common and important consideration is that of “physiologic hypertrophy of adolescence”of the pituitary gland. This is a condition where in the pituitary gland and young people, most often in young postpubertal women, is enlarged and looks hyperplastic. The hyperplasia, or enlargement, usually improves with age.

Some endocrine disorders that result in tumors probably start out as hyperplasia. For example, parathyroid hyperplasia may be the precursor lesion to parathyroid adenoma in patients with multiple endocrine neoplasia. The same may be true of the elect in producing cells in the pituitary gland prior to the development of a prolactinoma in these patients. Patients with McCune-Albright syndrome often develop acromegaly. In these patients, there is a spectrum of abnormalities within the pituitary gland ranging from hyperplasia, to nodular hyperplastic changes, to frank monoclonal tumors that seem to be derived from a single parent cell. This disease process serves as a “model” for the pathogenesis of tumors in patients with genetic disorders. First, the abnormal gene results in the tendency to develop hyperplasia. Something happens in affected cells to cause the development of hyperplasia. Then, one of the hyperplastic cells may develop a second mutation that leads to tumor formation.

In all cases, hyperplasia can be associated with diffuse pituitary enlargement evident on MRI imaging of the gland. On coronal sections through the pituitary the gland often looks trapezoidal in shape. On sagittal sections that gland may appear rounded. Contrast enhancement fails to demonstrate findings characteristic of pituitary adenoma and the entire gland usually enhances with gadolinium. Occasionally, the hyperprolactinemia is sufficiently large because visual field deficit’s and even headaches.

Treatment of pituitary hyperplasia depends on the underlying cause. Postmenopausal women should probably be treated with estrogen replacement. Men with hypogonadism should probably be treated with androgens. Primary hypothyroidism should definitely be treated with thyroxine. Estrogens might need to be discontinued in young women taking oral contraceptive pills. Hormone hypersecretory states should be managed based on the underlying cause. Physiologic hypertrophy of the pituitary gland does not require treatment. Idiopathic hyperplasia can probably be observed without intervention unless surgery is required to reverse visual field deficits. Rarely, a patient with hyperplasia due to target gland failure does not experience resolution of the hyperplasia, headaches, and associated visual field deficits despite target gland hormone replacement. In these patients, surgery may be required to restore vision. Generally, I do not recommend surgery in attempt to resolve headaches. Instead, I prefer that patients are referred to a neurologist with an emphasis or focus on management of headaches as medical therapy may obviate the need for surgery. Furthermore, headaches are common in the general population and there is no guarantee that surgery will alleviate the headaches and all patients with hyperplasia because the headaches might be due to some other pathophysiological mechanism. One other consideration, and an important reason to try to avoid surgery if possible, is that treatment of hyperplasia may result in hypopituitarism. Furthermore, if there is any residual pituitary tissue the disease process my recur. In my experience, surgery resulting in hypopituitarism and diabetes insipidus is not a worthwhile “trade” in attempt to resolve radiographic findings of hyperplasia, even in the presence of headaches, because those headaches might be resolved with medical management. It’s all about managing the risks and benefits and determining the best course of action that results in the least amount of harm.

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