 FOLDER 21.3 Clinical Correlation: Pathologies Associated with ADH Secretion chapter 21 Endocrine Organs PI N EAL G LAN D 753 The absence or reduced production of ADH leads to a condition known as diabetes insipidus, which is char-acterized by polyuria (production of large volumes of di-luted urine—up to 20 L per day) with hypotonic and tasteless (insipid) urine. Individuals with this condition have extreme thirst, which allows them to counteract the loss of water by drinking large amounts of fluids. This dis-ease commonly results from head injuries, tumors, or other lesions that can damage the hypothalamus or pos-terior lobe of the pituitary gland. This form of the disease is classified as hypothalamic diabetes insipidus in contrast to nephrogenic diabetes insipidus, in which secretion of the ADH is normal or elevated, but there is a lack of renal response to circulating levels of ADH. Nephrogenic diabetes is usually a congenital disorder re-lated to the mutation of the aquaporins-2 (AQP-2) water channels gene or different ADH V2 receptor mutations in kidney tubules. Hypothalamic diabetes insipidus is usu-ally treated by administration of synthetic analogs of ADH (desmopressin), whereas the treatment of the nephro-genic type of this disease is aimed at reducing the volume of urine output. Abnormally high levels of ADH are found in the syn-drome of inappropriate antidiuretic hormone secre-tion (SIADH), which is characterized by hyponatremia (low serum levels of sodium), decreased serum osmolality asso-ciated with excessive urine sodium excretion, and elevated urine osmolality. In SIADH, the elevated level of ADH in-creases the absorption of water, thereby leading to produc-tion of concentrated urine, inability to excrete water, and hyponatremia that results from excess water rather than sodium deficiency. The increase in ADH secretion may be related to CNS disorders (tumors, injuries, infections, or cerebrovascular accidents); pulmonary diseases (pneumo-nia, chronic obstructive pulmonary disease, a lung abscess, or tuberculosis); tumors that secrete ADH (small-cell carci-noma of the lung, tumors of the pancreas, thymoma, or lym-phomas); and certain drugs (anti-inflammatories, nicotine, diuretics, and many others). Treatment of SIADH depends on the underlying etiology and includes fluid restrictions as well as pharmacological treatment. An ADH V2–receptor antagonist (Conivaptan) is now available to improve hy-ponatremia and to increase the free water diuresis without loss of other ions in the urine of patients with SIADH. TABLE Hypothalamic Regulating Hormones21.5 Hormone Composition Source Major Functions Growth hormone– releasing hormone (GHRH) Two forms in human: polypeptides containing 40 and 44 amino acids Cell bodies of neurons located in the arcuate nucleus of hypothalamus Stimulates secretion and gene expression of GH by somatotropes Somatostatin Two forms in human: polypeptides containing 14 and 28 amino acids Cell bodies of neurons located in the periventricular, paraven-tricular, and  arcuate nuclei of the hypothalamus Inhibits secretion of GH by somatotropes, inhibits insulin secretion by B cells of pancreatic islets Dopamine Catecholamine (amino acid derivative) Cell bodies of neurons located in the arcuate nucleus of hypothalamus Inhibits secretion of PRL by lactotropes Corticotropin-releasing hormone (CRH) Polypeptide containing 41 amino acids Cell bodies of neurons located in the arcuate, periventricular, and medial paraventricular nuclei of hypothalamus Stimulates secretion of ACTH by corticotropes; stimulates gene expression for POMC in corticotropes Gonadotropin-releasing hormone (GnRH) Polypeptide containing 10 amino acids Cell bodies of neurons located in the arcuate, ventromedial, dorsal, and  paraventricular nuclei of hypothalamus Stimulates secretion of LH and FSH by gonadotropes Thyrotropin-releasing hormone (TRH) Polypeptide containing 3 amino acids Cell bodies of neurons located by the ventromedial, dorsal, and paraventricular nuclei of hypothalamus Stimulates secretion and gene expression of TSH by thyrotropes; stimulates synthesis and secretion of PRL