This chapter describes drugs used for hormonal replacement and for inhibition of hormonal secretion from the pituitary, thyroid, parathyroid, and adrenal glands. Before reading Chapters 51 and 52, review the introduction to Unit XVII, which describes the locations of the endocrine glands and the hormones they secrete. Knowledge of the various endocrine (ductless glands that produce internal secretions that flow to all parts of the body) hormones and their functions facilitates an understanding of the drugs that act on the endocrine glands.

Pituitary Gland

Anterior Lobe

The pituitary gland, or hypophysis, has an anterior and a posterior lobe. The anterior pituitary gland, called the adenohypophysis, secretes the following hormones that target glands and tissues:

• Growth hormone (GH), which stimulates growth in tissue and bone

• Thyroid-stimulating hormone (TSH), which acts on the thyroid gland

• Adrenocorticotropic hormone (ACTH), which stimulates the adrenal gland

• Gonadotropins (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), which affect the ovaries.

Drugs with adenohypophyseal properties used to stimulate or inhibit glandular activity are discussed according to their therapeutic use. The negative feedback system that controls the amount of hormonal secretion from the pituitary gland and the target gland is discussed in the introduction to Unit XVII.

Growth Hormone

Two hypothalamic hormones regulate GH: (1) growth hormone–releasing hormone (GH-RH) and (2) growth hormone–inhibiting hormone (GH-IH; somatostatin). 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. Subcutaneous (subQ) or intramuscular (IM) administration of GH is necessary.

If a child’s height is well below the standard for a specified age, GH deficiency may be diagnosed, and dwarfism can result. Growth hormone replacement is very expensive; therefore, various tests are performed to determine if this therapy is essential. Because GH acts on newly forming bone, it must be administered before the epiphyses are fused. Administration of GH over several years can increase height by a foot. Prolonged GH therapy can antagonize insulin secretion and eventually cause diabetes mellitus. Athletes should be advised not to take GH to build muscle and physique because of its effects on blood sugar and other side effects.

Drug Therapy: Growth Hormone Deficiency

Somatropin (Genotropin) is a growth hormone used to treat growth failure in children because of pituitary GH deficiency. Somatropin is a product that has the identical amino acid sequence as human growth hormone. 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.

Drug Therapy: Growth Hormone Excess

Gigantism (excessive growth during childhood) and acromegaly (excessive growth after puberty) can occur with GH hypersecretion and are frequently caused by a pituitary tumor. If the tumor cannot be destroyed by radiation, the prolactin-release inhibitor bromocriptine can inhibit the release of GH from the pituitary gland.

Octreotide (Sandostatin) is a potent synthetic somatostatin used to suppress GH release. It can be used alone or with surgery or radiation. This drug is expensive. GI side effects are common. This drug can also be used for severe diarrhea resulting from carcinoid tumors.

Table 51-1 lists the drugs used to replace or inhibit GH and their dosages, uses, and considerations.

TABLE 51-1

ANTERIOR AND POSTERIOR PITUITARY HORMONES

GENERIC (BRAND)	ROUTE AND DOSAGE	USES AND CONSIDERATIONS
Anterior Lobe
*Growth Hormone (GH)*
somatropin (Nutropin, Genotropin)	C: subQ/IM: Nutropin: 0.006 mg/kg/d; Genotropin: 0.04 mg/kg in 6-7 equal daily doses; max: 0.08 mg/kg/wk	For growth hormone deficiency. Promotes bone growth at epiphyseal plates of long bones. Pregnancy category: Nutropin: C; Genotropin: B; PB: 20%; : 15-60 min
*Growth Hormone Suppressant Drugs*
bromocriptine mesylate (Parlodel)	A: PO: 1.25-2.5 mg/d for 3 d; range: 10-30 mg/d; max: 100 mg/d	For acromegaly. Also used with pituitary radiation or surgery to decrease GH levels. Decreases lactation and prolactinoma. Pregnancy category: B; PB: 93%; : 3-6 h
octreotide acetate (Sandostatin)	A: subQ: 50-100 mcg t.i.d.	For acromegaly. To treat severe diarrhea associated with metastatic carcinoid and other tumors. Pregnancy category: B; PB: 65%; : 1.5 h
lanreotide acetate (Somatuline Depot)	A: subQ: Initially 90 mg q4wk for 3 mo; then 60-120 mg q4wk for 4 mo	To suppress GH. Monitor glucose levels. Pregnancy category: C; PB: 69%-78%; : 23-30 d
*Thyroid-Stimulating Hormone (TSH)*
thyrotropin (Thyrogen)	Thyroid cancer: A: IM: 0.9 mg into gluteus maximus, repeat in 24 h for 2 doses; max: 0.9 mg/d	For thyroid cancer. . Radioiodine study follows last injection. Pregnancy category: C; PB: UK; : 15-35 h
*Adrenocorticotropic Hormone (ACTH)*
corticotropin (H.P. Acthar gel)	See Prototype Drug Chart 51-1.
cosyntropin (Cortrosyn)	A/C: >2 y: IM/IV: 0.25 mg over 2 min or slow infusion over 6 h C: <2 y: IM/IV: 0.125 mg slow infusion over 6 h	For diagnostic testing to differentiate between pituitary and adrenal cause of adrenal insufficiency. Obtain plasma cortisol level before and 30 min after administration. Pregnancy category: C; PB: UK; : 15 min
Posterior Lobe
*Antidiuretic Hormone (ADH)*
desmopressin acetate (DDAVP, Stimate)	DDAVP: A: Intranasal: 0.1-0.4 mL/d in divided doses Stimate: A: subQ/IV: 0.2-0.4 mcg A/C: >11 mo: intranasal: 150 mcg/kg	For DI, hemophilia A, and von Willebrand disease. Can have a long duration of action (5-21 h). Pregnancy category: B; PB: UK; : 1.5-2.5 h
vasopressin (aqueous) (Pitressin)	Diabetes insipidus: A: subQ/IM: 5-10 units, b.i.d./q.i.d. C: subQ/IM: 2.5-10 units, b.i.d./q.i.d.	For DI. For relief of intestinal distention. Decreases GI bleeding from esophageal varices. Can also be given intranasally. Promotes reabsorption of water from renal tubules. Duration of action is 2-8 h. Pregnancy category: C; PB: UK; : 15 min
demeclocycline (Declomycin)	A: PO: 600 mg/d in 3-4 divided doses	For treatment of SIADH. Inhibits ADH-induced water reabsorption in renal distal tubules. Closely monitor sodium levels. Pregnancy category: C; PB: 99%; : 12 h
conivaptan (Vaprisol)	A: IV: LD 20 mg over 30 min; maint: 20 mg continuous IV over 24 h; then 20 mg/d for 1-3 d; max: 4 days therapy	For hypervolemic hyponatremia associated with SIADH. Closely monitor sodium levels. Pregnancy category: C; PB: 99%; : 5 h
tolvaptan (Samsca)	A: PO: Initially 15 mg/d; then 15-30 mg/d; max: 60 mg/d	For hyponatremia associated with SIADH. Closely monitor sodium levels. Pregnancy category: C; PB: 99%; : 12 h

A, Adult; ADH, antidiuretic hormone; b.i.d., twice a day; C, child; d, day; DI, diabetes insipidus; GI, gastrointestinal; h, hour; IM, intramuscular; IV, intravenous; LD, loading dose; min, minute; NSS, normal saline solution; PB, protein-binding; PO, by mouth; q.i.d., four times a day; subQ, subcutaneous; , half-life; t.i.d., three times a day; UK, unknown; wk, week; y, year; >, greater than; <, less than.

Thyroid-Stimulating Hormone

The adenohypophysis secretes thyroid-stimulating hormone (TSH) in response to thyroid-releasing hormone (TRH) from the hypothalamus, and TSH stimulates the thyroid gland to release thyroxine (T₄) and triiodothyronine (T₃, or liothyronine). Excess TSH secretion can cause hyperthyroidism, and a TSH deficit can cause hypothyroidism. Hypothyroidism may be caused by a thyroid gland disorder (primary cause) or a decrease in TSH secretion (secondary cause). Thyrotropin (Thytropar), a purified extract of TSH, is used as a diagnostic agent to differentiate between primary and secondary hypothyroidism (see Table 51-1).

Adrenocorticotropic Hormone

The hypothalamus releases corticotropin-releasing factor (CRF), which stimulates the pituitary corticotrophs to secrete adrenocorticotropic hormone (ACTH). ACTH secretion stimulates the release of glucocorticoids (cortisol), mineralocorticoids (aldosterone), and androgen from the adrenal cortex. Usually ACTH and cortisol secretions follow a diurnal rhythm in which the ACTH and cortisol secretion is higher in the early morning and then decreases throughout the day. Stresses such as surgery, sepsis, and trauma override the diurnal rhythm, causing an increase in secretions of ACTH and cortisol.

The ACTH drug corticotropin (Acthar) is used to diagnose adrenal gland disorders, to treat adrenal gland insufficiency, and as an antiinflammatory drug in the treatment of allergic response. Administration of ACTH intravenously (IV) should increase the serum cortisol level in 30 to 60 minutes if the adrenal gland is functioning. If steroid deficiency is caused by pituitary insufficiency, ACTH should eventually stimulate cortisol production. ACTH decreases the symptoms of multiple sclerosis during its exacerbation phase. Prototype Drug Chart 51-1 lists the pharmacologic data for repository corticotropin.

Prototype Drug Chart 51-1

Repository Corticotropin

Drug Class	Dosage
Pituitary adrenocorticotropic hormone Trade Name: H.P. Acthar Gel Pregnancy Category: C	Inflammation: A/C: subQ/IM: 40-80 units, q24-72h; max: 80 units/d Acute multiple sclerosis (MS): A: subQ/IM: 80-120 units/d for 2-3 wk; max: 120 units/d
Contraindications	Drug-Lab-Food Interactions
Severe fungal infection, adrenal insufficiency, Cushing’s syndrome, HF, peptic ulcer, osterporosis, scleroderma, ocular herpes simplex, recent surgery Caution: Hepatic disease, psychiatric disorders, cardiac disease, diabetes mellitus, renal impairment, hypertension, hypothyroidism, myasthenia gravis	Drug: Increase potential for ulcer formation and hypoprothrombinemia with aspirin and NSAIDs; may increase potassium loss with thiazide and loop diuretics; barbiturates, phenytoin decrease corticotropin effects; estrogens increase corticotropin effects
Pharmacokinetics	Pharmacodynamics
Absorption: IM: Well absorbed Distribution: PB: UK Metabolism: : 15-20 min Excretion: In urine	IM: Onset: <6 h Peak: 6-18 h Duration: 12-24 h IV: Onset: UK Peak: 1 h Duration: UK
Therapeutic Effects/Uses
To diagnose adrenocortical disorders; acts as antiinflammatory agent; to treat acute MS
Mode of Action: Stimulates adrenal cortex to secrete cortisol
Side Effects	Adverse Reactions
Nausea, vomiting, diarrhea, constipation, mood swing (euphoria to depression), petechiae, water and sodium retention, hypokalemia, hypocalcemia, acne	Edema, ecchymosis, osteoporosis, muscle atrophy, growth retardation, decreased wound healing, cataracts, glaucoma, seizures, menstrual irregularities, hypertension, Life-threatening: Ulcer perforation, pancreatitis

A, Adult; HF, heart failure; d, day; h, hour; IM, intramuscular; IV, intravenous; MS, multiple sclerosis; q.i.d., four times a day; subQ, subcutaneous; PB, protein-binding; , half-life; UK, unknown; wk, week; <, less than.

Pharmacokinetics

Corticotropin stimulates the adrenal gland to secrete corticosteroids. The aqueous and gel preparations are well absorbed into the circulation. Zinc is added to some formulations to slow the absorption rate. A portion of the drug is bound to protein; however, the percentage is unknown. The half-life of the drug is 15 to 20 minutes. It is excreted in the urine.

Pharmacodynamics

Corticotropin suppresses the inflammatory and immune responses. It is also prescribed to treat adrenal insufficiency secondary to inadequate corticotropin secretion. The drug is administered IM and IV. Its onset of action, peak concentration time, and duration of action are prolonged when it is injected IM. The IV preparation is in aqueous form; therefore its actions are faster than those of the gel and zinc-additive preparations.

Drug Interactions.

Corticotropin has numerous drug interactions. Diuretics and anti-Pseudomonas penicillins such as piperacillin can decrease the serum potassium level (hypokalemia). If the patient is taking a digitalis preparation and hypokalemia is present, digitalis toxicity can result. Phenytoin, rifampin, and barbiturates increase the metabolic rate, which can decrease the effect of the ACTH drug. Persons with diabetes may need increased insulin and oral antidiabetic (hypoglycemic) drugs because ACTH stimulates cortisol secretion, which increases the blood sugar level.

Posterior Lobe

The posterior pituitary gland, known as the neurohypophysis, secretes antidiuretic hormone (ADH) (vasopressin) and oxytocin. (Oxytocin is discussed in Chapter 54.)

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. Head injury and brain tumors resulting in trauma to the hypothalamus and pituitary gland can also cause DI. Fluid and electrolyte balance must be closely monitored in these patients, and ADH replacement may be needed. The ADH preparations vasopressin (Pitressin) and desmopressin acetate (DDAVP) can be administered intranasally or by injection.

Nursing Process

Patient-Centered Collaborative Care

Pituitary Hormones

Assessment

Obtain baseline vital signs for future comparison. Report abnormal results.

Determine patient’s urinary output and weight.

Assess patient for an infectious process. Corticotropin can suppress signs and symptoms of infection.

Note patient’s physical growth. Compare child’s growth with reported standards. Report findings.

Nursing Diagnoses

Ineffective health maintenance related to lack of ability to maintain drug regimen

Delayed growth and development related to deficient stimulation of growth hormone

Deficient knowledge related to inexperience with medication regimen

Planning

Patient will be free from pituitary disorder with appropriate drug regimen.

Nursing Interventions

Antidiuretic Hormone (ADH)

Monitor vital signs. Increased heart rate and decreased systolic pressure can indicate fluid volume loss resulting from decreased ADH production. With less ADH secretion, more water is excreted, decreasing vascular fluid (hypovolemia).

Record urinary output. Increased output can indicate fluid loss caused by a decrease in ADH.

Repository Corticotropin

Avoid administering corticotropin to patients with adrenocortical hyperfunction. Corticotropin stimulates the release of cortisol from the adrenal glands.

Monitor the growth and development of a child receiving corticotropin.

Observe patient’s weight. Check for edema if weight gain occurs. A side effect of repository corticotropin is sodium and water retention.

Watch carefully for adverse effects when corticotropin is discontinued. Dose should be tapered and not stopped abruptly, because adrenal hypofunction may result.

Check laboratory findings, especially electrolyte levels. Electrolyte replacement may be necessary.

Growth Hormone (GH)

Monitor blood sugar and electrolyte levels in patients receiving GH. Hyperglycemia can occur with high doses.

Patient Teaching

Adrenocorticotropic Hormone (ACTH)

Advise patient to adhere to drug regimen. Discontinuation of certain drugs, such as corticotropin, can cause hypofunction of gland being stimulated.

Direct patient to decrease salt intake to decrease or avoid edema. Potassium supplement may be needed.

Teach patient to report side effects such as muscle weakness, edema, petechiae, ecchymosis, decrease in growth, decreased wound healing, and menstrual irregularities.

Growth Hormone (GH)

Advise athletes not to take GH because of side effects. GH can be effective for children whose height is markedly below expected norm for their age. Because GH acts on newly forming bone, administer before epiphyses are fused.

Inform patient with diabetes to closely monitor blood sugar levels. Insulin regulation may be necessary.

Suggest that patient or family monitor patient’s growth rate.

Cultural Considerations

Individuals in some cultural groups may misunderstand purpose and use of GH. Health care provider needs to emphasize that these are not drugs for building muscles and that they can cause many serious side effects, such as diabetes mellitus, when abused.

Evaluation

Evaluate effectiveness of drug therapy.

When there is excess secretion of ADH from the posterior pituitary gland, the most common cause is small cell carcinoma of the lung. Medications, other malignancies, and stressors (e.g., pain, infection, anxiety, trauma) may also be causative factors. These conditions lead to an excessive amount of water retention expanding the intracellular volume. This increased fluid volume causes enhanced glomerular filtration and decreased tubular sodium reabsorption. Natriuresis (excretion of urinary sodium) results, leading to hyponatremia.

SIADH can be treated by fluid restriction, demeclocycline, conivaptan, and tolvaptan. Serum sodium levels must be monitored closely. Table 51-1 lists the drugs used for pituitary disorders and their dosages, uses, and considerations.

Thyroid Gland

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. Approximately 20% of circulating T₃ is secreted from the thyroid gland, and 80% of T₃ comes from the degradation of about 40% of T₄, which occurs in the periphery. T₄ and T₃ are carried in the blood by thyroxine-binding globulin (TBG) and albumin, which protect the hormones from being degraded. T₃ is more potent than T₄, and only unbound free T₃ and T₄ are active and produce a hormonal response.

Feedback mechanisms regulate T₄ and T₃ secretion from the thyroid gland. The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the release of TSH from the pituitary gland. TSH stimulates the synthesis and release of T₄ and T₃ from the thyroid gland. Excess free T₄ and T₃ inhibit the hypothalamus-pituitary-thyroid (HPT) axis, which results in decreased TRH and TSH secretion. Likewise, too low an amount of T₄ and T₃ increases the function of the HPT axis.

For thyroid deficiency (hypothyroidism), synthetic T₄ and T₃ may be prescribed, either alone or in combination. When the thyroid gland secretes an overabundance of thyroid hormones (hyperthyroidism), antithyroid drugs are usually indicated.

Hypothyroidism

Hypothyroidism, a decrease in thyroid hormone secretion, can have either a primary cause (thyroid gland disorder) or a secondary cause (lack of TSH secretion). Primary hypothyroidism occurs more frequently. Decreased T₄ and elevated TSH levels indicate primary hypothyroidism, the causes of which are acute or chronic inflammation of the thyroid gland, radioiodine therapy, excess intake of antithyroid drugs, and surgery. Myxedema is severe hypothyroidism in the adult; symptoms include lethargy, apathy, memory impairment, emotional changes, slow speech, deep coarse voice, edema of the eyelids and face, dry skin, cold intolerance, slow pulse, constipation, weight gain, and abnormal menses. In children, hypothyroidism can have a congenital (cretinism) or prepubertal (juvenile hypothyroidism) onset. Drugs containing T₄ and T₃, alone or in combination, are used to treat hypothyroidism.

Drug Therapy: Hypothyroidism

Levothyroxine sodium (Synthroid) is the drug of choice for replacement therapy for the treatment of hypothyroidism. It increases the levels of T₃ and T₄. Levothyroxine is also used to treat simple goiter and chronic lymphocytic (Hashimoto) thyroiditis.

Liothyronine (Cytomel) is a synthetic T₃ that has a short half-life and duration of action; it is not recommended for maintenance therapy. Liothyronine is better absorbed from the GI tract than levothyroxine, and because of its rapid onset of action and short half-life, it is frequently used as initial therapy for treating myxedema.

Liotrix (Thyrolar) is a mixture of levothyroxine sodium and liothyronine sodium in a 4 : 1 ratio. For treating hypothyroidism, there is no significant advantage to using liotrix over levothyroxine sodium alone, because levothyroxine converts T₄ to T₃ in the peripheral tissues.

Prototype Drug Chart 51-2 lists the pharmacologic data for levothyroxine.

Prototype Drug Chart 51-2

Levothyroxine Sodium

Drug Class	Dosage
Thyroid hormone Trade Names: T₄, Synthroid Pregnancy Category: A	A: PO: Initially: 25-50 mcg/d; maint: 50-200 mcg/d; A: IV: 50-100 mcg/d C: >12 y: PO: 2-3 mcg/kg/d
Contraindications	Drug-Lab-Food Interactions
Thyrotoxicosis, myocardial infarction, severe renal disease, adrenal insufficiency Caution: Cardiovascular disease, hypertension, angina pectoris, diabetes mellitus, osteoporosis	Drug: Increase cardiac insufficiency with epinephrine; increase effects of anticoagulants, tricyclic antidepressants, vasopressors, decongestants; decrease effects of antidiabetics (oral and insulin), digitalis products; decrease absorption with estrogens, antacids, cholestyramine, colestipol; increase risk of digitalis toxicity Food: Should be taken on an empty stomach, -1 h before eating
Pharmacokinetics	Pharmacodynamics
Absorption: PO: 50%-75% Distribution: PB: 99% Metabolism: : 6-7 days Excretion: In bile and feces	PO: Onset: UK Peak: 24 h-1 wk Duration: 1-3 wk IV: Onset: 6-8 h Peak: 24-48 h Duration: UK
Therapeutic Effects/Uses
To treat hypothyroidism, myxedema, and cretinism
Mode of Action: Increases metabolic rate, oxygen consumption, and body growth
Side Effects	Adverse Reactions
Nausea, vomiting, anorexia, diarrhea, cramps, tremors, nervousness, irritability, insomnia, headache, weight loss, diaphoresis, amenorrhea	Tachycardia, hypertension, palpitations, osteoporosis, seizures Life-threatening: Thyroid crisis, angina pectoris, cardiac dysrhythmias (atrial fibrillation), cardiovascular collapse

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Endocrine Drugs: Pituitary, Thyroid, Parathyroid, and Adrenal Disorders

Endocrine Drugs

Pituitary, Thyroid, Parathyroid, and Adrenal Disorders

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