34: Pituitary, Thyroid, and Parathyroid Pharmacology

CHAPTER 34 Pituitary, Thyroid, and Parathyroid Pharmacology

POSTERIOR PITUITARY HORMONES

The posterior lobe of the pituitary secretes two homologous peptide hormones, vasopressin and oxytocin. These hormones are synthesized in the hypothalamus and transported via the neurosecretory fibers of the stalk to the posterior pituitary, where they are stored and released. Both of these hormones are nonapeptides, and their structures are similar.

Vasopressin

Vasopressin (antidiuretic hormone [ADH]) acts on the kidney to increase water reabsorption. It increases total peripheral resistance and has an important role in the long-term control of blood pressure. Vasopressin also has a vasoconstrictor action that plays a role in the short-term regulation of arterial pressure. There are two subtypes of vasopressin receptors. V1 receptors, which are Gq/11 protein–linked, produce their action by stimulation of phospholipase C and formation of inositol triphosphate. This is the pathway responsible for the vasoconstrictor action of vasopressin. V2 receptors, which are Gs protein–linked, cause stimulation of adenylyl cyclase and increase cyclic adenosine 3′,5′-monophosphate (cAMP) formation. Stimulation of V2 receptors by vasopressin leads to its antidiuretic effect. Lack of ADH leads to diabetes insipidus, resulting in polyuria and polydipsia.

ANTERIOR PITUITARY HORMONES

Growth Hormone

Growth hormone (GH), also known as somatotropin, is the most abundant of the anterior pituitary hormones. The principal form of GH is a 191-amino acid single-peptide chain with two sulfhydryl bridges. GH for pharmacologic use is produced by recombinant DNA techniques and contains the 191-amino acid sequence of somatotropin, recombinant human GH, or 192 amino acids consisting of somatotropin plus an extra methionine at the amino terminal end. These preparations are equipotent.

Therapeutic uses

GH (somatrem, somatropin) is used in the treatment of growth failure in children (pituitary dwarfism), wasting in acquired immunodeficiency syndrome (AIDS), and somatotropin deficiency syndrome. Short-term treatment of GH-deficient adults results in increased lean body mass, decreased fat mass, increased exercise tolerance, and improved psychological well-being. It is sometimes abused by athletes6 or used for its antiaging effect. GH is a potent anabolic agent and may have a role in clinical management of burn injuries. The GH-releasing hormone analogue sermorelin is used to treat GH deficiency in children who have growth retardation and diagnostically to determine the GH-releasing capacity of the pituitary. Octreotide, a somatostatin analogue that inhibits GH release, is approved for use in treating symptoms of vasoactive intestinal tumors, metastatic carcinoid tumors, and acromegaly. Other uses include AIDS-associated diarrhea and esophageal varices. Pegvisomant, a competitive antagonist of GH, is used to treat acromegaly.

Adverse effects

GH may induce relative insulin resistance. It has been documented to cause diabetes in AIDS patients16 and decreased insulin sensitivity that is dose-dependent, with a possible increase in type 2 diabetes in children.5 It may cause scoliosis in children. Arthralgia, especially in the hands and wrist, may occur. Patients may have headaches, especially in the first few months of therapy, and should be carefully observed (monitored) because of the possibility of intracranial hypertension.

Prolactin

Prolactin is an anterior pituitary hormone that is similar in structure to GH. Prolactin increases the growth of the secretory epithelium in the breast and stimulates the production of milk. Although prolactin is not used clinically, the secretion of prolactin can be altered by certain drugs. Because dopamine inhibits prolactin release (Table 34-2), drugs that affect dopamine levels or dopamine receptors in the pituitary affect prolactin release. Bromocriptine and cabergoline are dopamine-receptor agonists that are used to inhibit prolactin release and reduce the size of pituitary prolactin-releasing tumors.

TABLE 34-2 Hypothalamic Inhibitory Releasing Factors, Anterior Pituitary Hormones Inhibited, and Target Glands

HYPOTHALAMIC HORMONE PITUITARY HORMONE INHIBITED TARGET ORGAN
Dopamine Prolactin Breast
Somatostatin Growth hormone Liver, bone, other

THYROID HORMONES

The active principles of the thyroid gland are iodine-containing amino acid derivatives of thyronine. They are formed from iodinated tyrosine residues. The structures are shown in Figure 34-1.

Synthesis of Thyroid Hormones

The synthesis of thyroid hormones is shown schematically in Figure 34-2. The first step is uptake of iodide by the thyroid gland. This step may be inhibited by ions of similar size and charge such as perchlorate. Iodide uptake is followed by oxidation of iodide to hypoiodite and iodination of tyrosyl groups of thyroglobulin to form iodotyrosyl groups. Tyrosine residues within the thyroglobulin molecule may be monoiodinated to monoiodotyrosine (MIT) or diiodinated to form diiodotyrosine (DIT). This step is catalyzed by thyroperoxidase and is rapid. Iodotyrosyl residues are coupled to form iodothyronyl residues within thyroglobulin. This may be either MIT plus DIT to form T3 or DIT plus DIT to form T4. The ratio of T4 to T3 formed is approximately 4 : 1. The coupling of iodotyrosyl groups is also catalyzed by peroxidase enzyme. Thyroid hormones are released by proteolysis of thyroglobulin. Most of the hormone released is T4, which is converted to T3 in peripheral tissues by iodothyronine deiodinases. T3 is about four times more potent than T4.

THYROID DISORDERS

Worldwide, the most common cause of thyroid disorders is iodine deficiency. In the United States, the leading cause of hypothyroidism is Hashimoto’s thyroiditis, an autoimmune disease. Graves’ disease (diffuse toxic goiter), also an autoimmune disorder, is the most common cause of hyperthyroidism in the United States.

Hypothyroidism

Thyroid deficiency during development causes cretinism, which is characterized by gross retardation of growth and mental deficiency. In an adult, thyroid deficiency results in hypothyroidism and, in more severe cases, myxedema. Hypothyroidism is a common endocrine disorder affecting 1.4% to 2% of women and 0.1% to 0.2% of men. The prevalence of overt and subclinical hypothyroidism is significantly greater in women than in men and increases dramatically in women after age 40 years, affecting 5% to 10% of women older than 50 years.2 Subclinical hypothyroidism is common, especially among older women.15 It has been suggested that this condition may be associated with an increased mortality rate, particularly from cardiovascular disease and a subtle decrease in myocardial contractility.11 Subclinical hypothyroidism is associated with a small increase in low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol, changes that increase risk of atherosclerosis and coronary artery disease.10 Cognitive impairment occurs in hypothyroidism, and attention, motor speed, memory, and visual spatial organization all are significantly impaired.4 In addition, hypothyroidism is an important risk factor for carpal tunnel syndrome.14

Jan 5, 2015 | Posted by in General Dentistry | Comments Off on 34: Pituitary, Thyroid, and Parathyroid Pharmacology
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