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Kee: Pharmacology, 8th Edition

Chapter 51: Endocrine Drugs: Pituitary, Thyroid, Parathyroid, and Adrenal Disorders
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Chapter 51 discusses drugs used for hormonal replacement and for inhibition of hormonal
secretion from the pituitary, adrenal, thyroid, and parathyroid glands.

The anterior pituitary gland secretes the following hormones that target glands and
tissues: (a) growth hormone (GH), (b) thyroid-stimulating hormone (TSH), (c)
adrenocorticotropic hormone (ACTH), and (d) gonadotropins (follicle-stimulating
hormone [FSH] and luteinizing hormone [LH]).

Growth hormone does not have a specific target gland. It affects body tissues and bone;
GH replacement stimulates linear growth when there is a GH deficiency. Growth
hormone drugs cannot be given orally, because they are inactivated by gastrointestinal
enzymes.

Because GH acts on newly forming bone, it must be administered before the epiphyses
are fused.

Prolonged GH therapy can antagonize insulin secretion and eventually cause diabetes
mellitus.

Somatrem and somatropin are two growth hormones used to treat growth failure in
children because of pituitary GH deficiency.

Somatropin is contraindicated in pediatric patients who have growth deficiency due to


Prader-Willi syndrome and are severely obese or who have severe respiratory
impairment, because fatalities associated with these risk factors have been reported.

Gigantism and acromegaly can occur with GH hypersecretion and are frequently caused
by a pituitary tumor. The prolactin-release inhibitor bromocriptine can inhibit the release
of GH from the pituitary gland.

Octreotide is a potent synthetic somatostatin used to suppress GH release. GI side effects


are common.

Excess TSH secretion can cause hyperthyroidism, and a TSH deficit can cause
hypothyroidism.

ACTH secretion stimulates the release of glucocorticoids, mineralocorticoids, and


androgen from the adrenal cortex.

The ACTH drug corticotropin is used to diagnose adrenal gland disorders, to treat adrenal
gland insufficiency, and as an antiinflammatory drug in the treatment of allergic response.
Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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51-2

Corticotropin has numerous drug interactions. Persons with diabetes may need increased
insulin and oral antidiabetic drugs.

ADH promotes water reabsorption from the renal tubules to maintain water balance in the
body fluids.

When there is a deficiency of ADH, large amounts of water are excreted by the kidneys.
This condition, called diabetes insipidus (DI), can lead to severe fluid volume deficit and
electrolyte imbalances.

Fluid and electrolyte balance must be closely monitored in patients with DI, and ADH
replacement may be needed with the ADH preparations vasopressin and desmopressin
acetate.

SIADH can be treated by fluid restriction, demeclocycline, conivaptan, and tolvaptan.


Serum sodium levels must be monitored closely.

Thyroxine (T4) and triiodothyronine (T3) are secreted by the thyroid gland. The functions
of T4 and T3 are to regulate protein synthesis and enzyme activity and to stimulate
mitochondrial oxidation. Feedback mechanisms regulate T4 and T3 secretion from the
thyroid gland.

Decreased T4 and elevated TSH levels indicate primary hypothyroidism. Myxedema is


severe hypothyroidism in the adult; in children, hypothyroidism can have a congenital
(cretinism) or prepubertal (juvenile hypothyroidism) onset.

Levothyroxine sodium is the drug of choice for replacement therapy for the treatment of
hypothyroidism. It increases the levels of T3 and T4.

Liothyronine is a synthetic T3 that has a short half-life and duration of action; it is not
recommended for maintenance therapy.

Many drug interactions are associated with T4 and T3 drugs.

Hyperthyroidism is an increase in circulating T4 and T3 levels. Hyperthyroidism may be


mild with few symptoms or severe, as in thyroid storm in which death may occur from
vascular collapse. Graves disease, or thyrotoxicosis, is the most common type of
hyperthyroidism.

The purpose of antithyroid drugs is to reduce the excessive secretion of thyroid hormones
(T4 and T3) by inhibiting thyroid secretion.

Thiourea derivatives are the drugs of choice used to decrease thyroid hormone
production. This drug group interferes with synthesis of thyroid hormone.

Propylthiouracil and methimazole are effective thioamide antithyroid drugs. They are
useful for treating thyrotoxic crisis and in preparation for subtotal thyroidectomy.
Prolonged use of thioamides may cause a goiter.

Antithyroid drugs interact with many other drugs.


Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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51-3

The parathyroid glands secrete parathyroid hormone (PTH), which regulates calcium
levels in the blood. The action of PTH is to promote calcium absorption from the GI
tract, promote reabsorption of calcium from the renal tubules, and activate vitamin D.

Calcitriol is a vitamin D analogue that promotes calcium absorption from the GI tract and
secretion of calcium from bone to the bloodstream.

Corticosteroids promote sodium retention and potassium excretion. Because of their


influence on electrolytes and carbohydrate, protein, and fat metabolism, a deficiency of
corticosteroids can result in serious illness or death.

A decrease in corticosteroid secretion is called adrenal hyposecretion (adrenal


insufficiency, or Addisons disease), and an increase in corticosteroid secretion is called
adrenal hypersecretion (Cushings syndrome).

Glucocorticoids are used to treat many diseases and health problems, including
inflammatory, allergic, and debilitating conditions.

The side effects and adverse reactions of glucocorticoids that result from high doses or
prolonged use include increased blood sugar, abnormal fat deposits in the face and trunk,
decreased extremity size, muscle wasting, edema, sodium and water retention,
hypertension, euphoria or psychosis, thinned skin with purpura, increased intraocular
pressure, peptic ulcers, and growth retardation.

When drug therapy is discontinued, the dose should be tapered to allow the adrenal
cortex to produce cortisol and other corticosteroids. Abrupt withdrawal of the drug can
result in severe adrenocortical insufficiency.

The antineoplastic hormone antagonists mitotane and aminoglutethimide inhibit


glucocorticoid synthesis. Aminoglutethimide is frequently prescribed for temporary
treatment of selected patients with Cushings syndrome.

Mineralocorticoids secrete aldosterone. Aldosterone is controlled by the reninangiotensin system. These hormones maintain fluid balance.

Fludrocortisone is an oral mineralocorticoid. It can cause a negative nitrogen balance;


therefore, a high-protein diet is usually indicated. Serum potassium levels should be
monitored.

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.