Abnormalities in the signaling mechanisms that coordinate and control the function of multiple organs and biological processes are the bases of many endocrine diseases. Classical biochemistry, physiology, and advances in cell and molecular biology and genetics combined with clinical observations are able to explain the mechanisms of hor-monal action and endocrine diseases. Endocrine diseases can be classified into four major categories:  Hormone overproduction. The most common cause of hormone overproduction is an increase in the total num-ber of cells producing a specific hormone. An example of this mechanism is hyperthyroidism (Graves’ disease; see Folder 21.4). Briefly, the presence of abnormal antibodies that mimic the action of TSH stimulates a dramatic in-crease in the number of thyroid cells. In some instances, increased hormone secretion is related to genetic abnor-mality that affects regulation of hormone synthesis and re-lease. In addition, mutation in tumor suppressor genes and protooncogenes may lead to proliferation of mutant cells that produce the specific hormone. This commonly occurs in cells of the anterior lobe of the pituitary gland.  Hormone underproduction. Underproduction of hor-mones may result from destruction of an endocrine organ by a disease process (e.g., tuberculosis of the adrenal glands) or autoimmunity (e.g., Hashimoto’s disease in which abnormal antibodies target and destroy thyroid hormone–producing cells). Also, genetic abnormalities that lead to abnormal development of endocrine glands (e.g., hypogonadotropic hypogonadism), abnormal hormone synthesis (e.g., deletion of the GH gene), or abnormal reg-ulation of hormone secretion (e.g., hypoparathyroidism associated with mutation of the calcium-sensing receptor expressed on parathyroid cells) can cause decreased serum levels or lack of active hormones. Iatrogenic injury to endocrine glands such as occurs when the parathyroid gland is removed during thyroidectomy (thyroid gland removal) may also be responsible.  Altered tissue responses to hormones. This cate-gory of endocrine disease is often cause by a variety of genetic mutation in hormone receptors (e.g., TSH, LH, and PTH). In diabetic patients, the resistance to insulin in muscles and the liver is mainly caused by signals origi-nating from adipose tissue (see Chapter 9).  Tumors of endocrine glands. Most of the tumors of endocrine gland are hormonally active and are responsi-ble for hormone overproduction. However, some tumors of endocrine glands do not produce hormones, but com-press neighboring organs or cause destructions of other organs due to metastasis. An example of such a tumor is thyroid cancer that can metastasize throughout the body without presenting signs of thyroid hormone overpro-duction (hyperthyroidism). Hormones are used to treat endocrine diseases. A com-mon use is as hormone replacement therapies when a specific endocrine gland is not developed or ceases to produce the required hormone. Hormones and their syn-thetic analogs can be used to suppress the effects of other hormones. In general, thyroid and steroid hormones can be administered orally, whereas protein hormones (e.g., insulin, GH) need to be injected. Recent technological innovations including computerized mini-pumps and depot intramuscular injections have made therapy more manage-able for patients.
 FOLDER 21.2 Clinical Correlation: Principles of Endocrine Diseases in osmolality or a decrease in blood volume stimulates ADH release. Additionally, the cell bodies of the hypothalamic secretory neurons may also serve as osmoreceptors, initiating ADH release. Pain, trauma, emotional stress, and drugs such as nicotine also stimulate release of ADH.