The pituitary gland sits in the skull in the bony sella turcica under a layer of dura mater. It has three lobes. The anterior lobe produces stimulating hormones in response to hypothalamic signals. The posterior lobe stores ADH and oxytocin. The intermediate lobe produces endorphins and enkephalins that modulate pain perception.
Pituitary agents either mimic or antagonize specific pituitary hormones. They serve as replacement therapy, as diagnostic agents, and as blockers of anterior pituitary hormones. Growth hormone (GH) is the anterior pituitary hormone used most often pharmacologically.
Pituitary Agents: Generic and Brand Names
- Anterior pituitary hormone drugs
- Growth Hormone Agonists
- somatropin (Nutropin, Saizen, Humatrope)
- Growth Hormone Antagonists
- bromocriptine (Parlodel)
- lanreotide (Somatuline Depot)
- octreotide (Sandostatin)
- pegvisomant (Somavert)
- Other drugs affecting anterior pituitary hormones
- chorionic gonadotropin (Chorex)
- corticotropin (Acthar)
- cosyntropin (Cortrosyn)
- menotropin (Pergonal)
- thyrotropin alfa (Thyrogen)
- Growth Hormone Agonists
- Posterior Pituitary Hormone Drugs
- conivaptan (Vaprisol)
- desmopressin (DDAVP)
- tolvaptan (Samsca)
Growth Hormone Agonists
GH agonists replace human GH to drive linear skeletal growth, growth of internal organs, protein synthesis, and the other processes normal growth depends on. Somatropin (Nutropin, Saizen, Genotropin, Serostim) and somatropin rDNA origin (Zorbtive) are the agents used for GH replacement.
Disease Spotlight: GH Deficiency
GH deficiency often shows as hypopituitarism before any other sign appears. Causes include developmental abnormalities, congenital defects of the pituitary, circulatory disturbances (hemorrhage), acute or chronic pituitary inflammation, and pituitary tumors. In children, GH deficiency produces dwarfism and short stature. Somatotropin deficiency syndrome (SDS) is the adult form, seen with pituitary tumors or trauma or in adults treated for GH deficiency as children, where the pituitary shuts down somatotropin production.
Indications
Long-term treatment of children with growth failure from various deficiencies, girls with Turner's syndrome, AIDS wasting and cachexia, GH deficiency in adults, and growth failure in children small for gestational age who do not achieve catch-up growth by 2 years of age.
Pharmacokinetics
Here are the characteristic interactions of GH agonists and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IM, subcutaneous | Varies | 5-7.5 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 15-20 min | Liver | Urine, Feces |
Contraindications and Cautions
Do not use with allergy to any drug component. Somatropin is contraindicated for growth promotion once the epiphyses are closed, and active malignancy and acute critical illness are also contraindications (FDA Genotropin label). Watch for a new limp or hip or knee pain, which can signal slipped capital femoral epiphysis, and check thyroid function periodically since untreated hypothyroidism blunts the growth response. Abdominal surgery and acute illness from open heart surgery complications raise healing problems. Avoid in pregnancy or lactation for potential fetal effects.
Adverse Effects
Antibodies to GH may develop. Inflammation and autoimmune-type reactions (swelling, joint pain) and endocrine reactions (hypothyroidism, insulin resistance) occur.
Interactions
Metabolism changes with drugs using the P450 liver enzyme system.
Nursing Considerations
Before starting, screen for allergy, pregnancy, serious infection after open heart surgery, and other cautions. Get baseline height, weight, thyroid function tests, glucose tolerance tests, and GH levels. Reconstitute per the manufacturer's directions (products vary) and give IM or subcut as ordered. Monitor response, thyroid function, glucose tolerance, and GH levels periodically and adjust the dose to the response. Teach storage, preparation, injection technique, drug effects, and the warning signs to report. Evaluate against return of GH levels to normal and normal growth and development, and watch for nutritional imbalance and hypothyroidism.
Growth Hormone Antagonists
GH antagonists treat GH hypersecretion (hyperpituitarism) caused by pituitary tumors. Octreotide and lanreotide are somatostatin analogues, more potent than somatostatin at inhibiting GH release with less inhibition of insulin release, and are used in its place. Bromocriptine is a semisynthetic ergot alkaloid and dopamine agonist used often for acromegaly, sometimes as an adjunct to irradiation.
Disease Spotlight: Hyperpituitarism
GH hypersecretion is usually caused by pituitary tumors and can occur at any point in life. Gigantism occurs before the epiphyseal plates of the long bones fuse, accelerating linear skeletal growth; these individuals can reach 7 to 8 feet in height with fairly normal body proportions. Acromegaly is the form after epiphyseal closure in adults: linear growth is impossible, so excess GH enlarges the peripheral parts of the body (hands and feet) and internal organs (heart).
Therapeutic Action
GH antagonists act directly on postsynaptic dopamine receptors in the brain to inhibit GH secretion.
Indications
Parkinson's disease, hyperprolactinemia associated with pituitary adenomas, female infertility associated with hyperprolactinemia, and acromegaly; short-term treatment of amenorrhea or galactorrhea.
Pharmacokinetics
Here are the characteristic interactions of GH antagonists and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| PO | Varies | 1-3 h | 14 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 60-90 min | Liver | Bile |
Contraindications and Cautions
Allergy to any drug component, and pregnancy or lactation for potential fetal effects. Use caution in diabetes and thyroid dysfunction, which blocking GH can worsen.
Adverse Effects
CNS: headache. CV: sinus bradycardia, arrhythmias. GI: nausea, vomiting, abdominal cramps, constipation, diarrhea, acute cholecystitis, cholestatic jaundice, biliary tract obstruction, pancreatitis. Others: decreased glucose tolerance, inflammation at injection sites.
Interactions
Erythromycin increases bromocriptine toxicity. Phenothiazines decrease bromocriptine effectiveness. Opioids require higher pegvisomant doses.
Nursing Considerations
Screen for allergy, other endocrine disturbances, and pregnancy or lactation. Get baseline orientation, affect, and reflexes; blood pressure, pulse, and orthostatic blood pressure; abdominal exam; glucose tolerance tests; and GH levels. Reconstitute per the manufacturer's directions and give IM or subcut as ordered. Inject lanreotide deep into the subcutaneous fat of the superior quadrant of the buttocks, alternating right to left, to ensure delivery and prevent local reactions. Arrange baseline and periodic gallbladder ultrasound for patients on octreotide or lanreotide to catch gallstone development; cholelithiasis is common with long-term octreotide, and the manufacturer reports new gallstones in about 22% of patients treated for 12 months or longer (FDA Sandostatin label). Monitor thyroid function, glucose tolerance, and GH levels periodically. Evaluate against return of GH levels to normal.
Drugs Affecting Posterior Pituitary Hormones
The posterior pituitary stores two hormones made by the hypothalamus: antidiuretic hormone (ADH, vasopressin) and oxytocin. ADH has antidiuretic, hemostatic, and vasopressor properties and is the hormone lost in diabetes insipidus, where the patient produces a large volume of dilute, glucose-free urine.
Therapeutic Action
Posterior pituitary agents make the cortical and medullary collecting duct permeable to water, increasing water reabsorption and decreasing urine formation (pressor and antidiuretic effect), and they raise levels of clotting factor VIII.
Indications
Neurogenic diabetes insipidus and hemophilia A.
Pharmacokinetics
Here are the characteristic interactions of posterior pituitary agent and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | 1 h | 60-90 min | 7 h |
| IV, subcutaneous | 30 min | 90-120 min | Varies |
| Nasal | 15-60 min | 1-5 h | 5-21 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 7.8 min, 75.5 min (IV) 1.5-2.5 h (oral) 3.3-3.5 h (nasal | Tissues | Unknown |
Contraindications and Cautions
Allergy to any drug component. Severe renal dysfunction can alter the drug's effects. Known vascular disease can be worsened by the drug's effect on vascular smooth muscle. Avoid in pregnancy (risk of premature uterine contractions) and lactation (potential neonatal effects).
Adverse Effects
Water intoxication: drowsiness, lightheadedness, headache, coma, convulsions. GI: abdominal cramps, flatulence, nausea, vomiting, constipation, dry mouth. Local reaction at the injection site.
Interactions
Carbamazepine and chlorpropamide increase antidiuretic effects with desmopressin. Digoxin, ACE inhibitors, ARBs, and potassium-sparing diuretics raise the risk of hyperkalemia with tolvaptan and conivaptan. Telithromycin causes severe tolvaptan toxicity.
Nursing Considerations
Screen for allergy, pregnancy, and renal dysfunction. Get baseline skin assessment; orientation, affect, and reflexes; blood pressure and pulse; respirations and adventitious sounds; abdominal exam; renal function tests; and serum electrolytes. Monitor fluid volume for water intoxication and for excessive fluid loss. Watch patients with vascular disease for exacerbation. If given intranasally, check the nasal passages for ulceration, which can occur and affect absorption. Teach drug effects and the warning signs to report. Evaluate against maintenance of fluid balance, and watch for water intoxication and GI problems.
Frequently Asked Questions
What is the difference between a growth hormone agonist and antagonist? Agonists such as somatropin replace deficient growth hormone to drive linear growth in children who are not growing. Antagonists such as octreotide, lanreotide, and bromocriptine suppress excess growth hormone from a pituitary tumor in gigantism or acromegaly.
Why can't somatropin be used once the growth plates close? Once the epiphyses are fused, the long bones can no longer grow in length, so somatropin offers no height benefit and the FDA contraindicates it for growth promotion in that setting (FDA Genotropin label). Adults treated for childhood deficiency are reevaluated and switched to a lower adult dose if therapy continues.
Why do patients on octreotide need gallbladder monitoring? Octreotide slows gallbladder emptying, so gallstones and biliary sludge are common with long-term use. The manufacturer reports new gallstones in about 22% of patients treated for 12 months or longer, which is why baseline and periodic ultrasound is recommended (FDA Sandostatin label).
What is the difference between gigantism and acromegaly? Both come from growth hormone excess, usually a pituitary tumor. Gigantism happens before the growth plates fuse and produces very tall stature with normal proportions. Acromegaly happens after they fuse, so instead of height the hands, feet, face, and internal organs enlarge.
What is the main risk to watch for with posterior pituitary agents like desmopressin? Water intoxication. Because these agents make the kidneys reabsorb water, monitor for drowsiness, headache, lightheadedness, and in severe cases seizures, and track fluid balance and serum sodium.
How is lanreotide injected? Lanreotide depot is given deep into the subcutaneous fat of the upper outer quadrant of the buttock, alternating sides between doses to ensure delivery and limit local reactions.