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1. Describe clinical uses of selected hormones. 4. State major nursing considerations in the care
2. Differentiate characteristics and functions of of clients receiving specific hypothalamic and
anterior and posterior pituitary hormones. pituitary hormones.
3. Discuss limitations of hypothalamic and pituitary
hormones as therapeutic agents.
Reflect on:
Additional assessment questions to ask John and his mother.
Factors that might influence their desire for increased height and the use of growth hormone to
accomplish this.
If John uses growth hormone, outline some of the disadvantages and side effects.
Hypothalamus
Hypothalamic-releasing hormones
Posterior pituitary
ADH Kidneys
Anterior pituitary
Oxytocin Uterus
Breasts
test pituitary function and to stimulate growth in children to TSH deficiency in children being treated with growth hor-
with GHRH deficiency. mone. A long-acting somatostatin analog, octreotide (Sando-
Growth hormone release-inhibiting hormone (so- statin), may be used to treat acromegaly and TSH-secreting
matostatin) inhibits release of growth hormone. Although pituitary tumors.
originally isolated from the hypothalamus, it is found in Thyrotropin-releasing hormone (TRH) causes release
many tissues. It is distributed throughout the brain and of thyroid-stimulating hormone (TSH or thyrotropin) in re-
spinal cord, where it functions as a neurotransmitter. It sponse to stress, such as exposure to cold. TRH may be used
is also found in the intestines and the pancreas (where it in diagnostic tests of pituitary function and hyperthyroidism.
regulates secretion of insulin and glucagon). Somatostatin Gonadotropin-releasing hormone (GnRH) causes re-
secretion is increased by several neurotransmitters, includ- lease of follicle-stimulating hormone (FSH) and luteinizing
ing acetylcholine, dopamine, epinephrine, GABA, and nor- hormone (LH). Several synthetic equivalents of GnRH are
epinephrine. used clinically.
In addition to inhibiting growth hormone, somatostatin also Prolactin-releasing factor is active during lactation after
inhibits other functions, including secretion of corticotropin, childbirth.
thyroid-stimulating hormone (TSH or thyrotropin), prolactin, Prolactin-inhibitory factor (PIF) is active at times other
pancreatic secretions (eg, insulin, glucagon), gastrointestinal than during lactation.
(GI) secretions (gastrin, cholecystokinin, secretin, vasoactive
intestinal peptide), GI motility, bile flow, and mesenteric blood
flow. Hypothalamic somatostatin blocks the action of GHRH Anterior Pituitary Hormones
and decreases thyrotropin-releasing hormone (TRH)-induced
release of TSH. Growth hormone stimulates secretion of so- The anterior pituitary gland produces seven hormones. Two
matostatin, and somatostatins effects on TSH may contribute of these, growth hormone and prolactin, act directly on their
CHAPTER 23 HYPOTHALAMIC AND PITUITARY HORMONES 327
target tissues; the other five act indirectly by stimulating target Decreased pituitary secretion of LH causes the corpus luteum
tissues to produce other hormones. to die and stop producing progesterone. Lack of progesterone
Corticotropin, also called ACTH, stimulates the adrenal causes slough and discharge of the endometrial lining as
cortex to produce corticosteroids. Secretion is controlled by menstrual flow. (Of course, if the ovum has been fertilized
the hypothalamus and by plasma levels of cortisol, the major and attached to the endometrium, menstruation does not
corticosteroid. When plasma levels are adequate for body occur.) In men, LH stimulates the Leydigs cells in the spaces
needs, the anterior pituitary does not release corticotropin between the seminiferous tubules. These cells then secrete
(negative feedback mechanism). androgens, mainly testosterone.
Growth hormone, also called somatotropin, stimulates Prolactin plays a part in milk production by nursing
growth of body tissues. It promotes an increase in cell size mothers. It is not usually secreted in nonpregnant women
and number, including growth of muscle cells and lengthen- because of the hypothalamic hormone PIF. During late
ing of bone, largely by affecting metabolism of carbohydrate, pregnancy and lactation, various stimuli, including suck-
protein, fat, and bone tissue. For example, it regulates cell di- ling, inhibit the production of PIF, and thus prolactin is syn-
vision and protein synthesis required for normal growth. In thesized and released.
children, levels of growth hormone rise rapidly during adoles- Melanocyte-stimulating hormone plays a role in skin
cence, peak in the 20s, then start to decline. Deficient growth pigmentation, but its function in humans is not clearly
hormone in children produces dwarfism, a condition marked delineated.
by severely decreased linear growth and, frequently, severely
delayed mental, emotional, dental, and sexual growth as well.
Deficient hormone in adults (less than expected for age) can Posterior Pituitary Hormones
cause increased fat, reduced skeletal and heart muscle mass, re-
duced strength, reduced ability to exercise, and worsened cho- The posterior pituitary gland stores and releases two hormones
lesterol levels (ie, increased low-density lipoprotein [LDL] that are synthesized by nerve cells in the hypothalamus.
cholesterol and decreased high-density lipoprotein [HDL] cho- Antidiuretic hormone (ADH), also called vasopressin,
lesterol), which increase risk factors for cardiovascular disease. functions to regulate water balance. When ADH is secreted,
Excessive growth hormone in preadolescent children pro- it makes renal tubules more permeable to water. This allows
duces gigantism, resulting in heights of 8 or 9 feet if untreated. water in renal tubules to be reabsorbed into the plasma and so
Excessive growth hormone in adults produces acromegaly, conserves body water. In the absence of ADH, little water is
which distorts facial features and is associated with an in- reabsorbed, and large amounts are lost in the urine.
creased incidence of diabetes mellitus and hypertension. Antidiuretic hormone is secreted when body fluids become
Thyrotropin (also called TSH) regulates secretion of thy- concentrated (high amounts of electrolytes in proportion to the
roid hormones. Thyrotropin secretion is controlled by a neg- amount of water) and when blood volume is low. In the first
ative feedback mechanism in proportion to metabolic needs. instance, ADH causes reabsorption of water, dilution of ex-
Thus, increased thyroid hormones in body fluids inhibit se- tracellular fluids, and restoration of normal osmotic pressure.
cretion of thyrotropin by the anterior pituitary and of TRH by In the second instance, ADH raises blood volume and arterial
the hypothalamus. blood pressure toward homeostatic levels.
FSH, one of the gonadotropins, stimulates functions of sex Oxytocin functions in childbirth and lactation. It initiates
glands. It is produced by the anterior pituitary gland of both uterine contractions at the end of gestation to induce child-
sexes, beginning at puberty. FSH acts on the ovaries in a cycli- birth, and it causes milk to move from breast glands to nipples
cal fashion during the reproductive years, stimulating growth so the infant can obtain the milk by suckling.
of ovarian follicles. These follicles then produce estrogen,
which prepares the endometrium for implantation of a fertil-
ized ovum. FSH acts on the testes to stimulate the production THERAPEUTIC LIMITATIONS
and growth of sperm (spermatogenesis), but it does not stimu-
late secretion of male sex hormones. Drug preparations of FSH There are few therapeutic uses for hypothalamic hormones
include urofollitropin (Fertinex), follitropin alfa (Gonal-F), and pituitary hormones. Most hypothalamic hormones are
and follitropin beta (Follistim). These drugs are used to stimu- used to diagnose pituitary insufficiency. Pituitary hormones
late ovarian function in the treatment of infertility. are not used extensively because most conditions in which
LH (also called interstitial cell-stimulating hormone) is they are indicated are uncommon; other effective agents are
another gonadotropin that stimulates hormone production by available for some uses; and deficiencies of target gland hor-
the gonads of both sexes. In women, LH is important in the mones (eg, corticosteroids, thyroid hormones, male or female
maturation and rupture of the ovarian follicle (ovulation). sex hormones) are usually more effectively treated with those
After ovulation, LH acts on the cells of the collapsed sac to pro- hormones than with anterior pituitary hormones that stimu-
duce the corpus luteum, which then produces progesterone late their secretion. However, the hormones perform impor-
during the last half of the menstrual cycle. When blood pro- tant functions when used in particular circumstances, and
gesterone levels rise, a negative feedback effect is exerted on drug formulations of most hormones have been synthesized
hypothalamic and anterior pituitary secretion of gonadotropins. for these purposes.
328 SECTION 4 DRUGS AFFECTING THE ENDOCRINE SYSTEM
INDIVIDUAL HORMONAL AGENTS formulation, is more commonly used to test for suspected
adrenal insufficiency.
Selected drugs are described below. Indications for use, Growth hormone is synthesized from bacteria by recom-
routes, and dosage ranges are listed in Drugs at a Glance: binant DNA technology. Somatropin (Humatrope) and soma-
Hypothalamic and Pituitary Agents. trem (Protropin) are therapeutically equivalent to endogenous
growth hormone produced by the pituitary gland. The main
clinical use of the drugs is for children whose growth is im-
Hypothalamic Hormones paired by a deficiency of endogenous hormone. The drugs are
ineffective when impaired growth results from other causes or
Gonadorelin (Factrel), goserelin (Zoladex), histrelin (Sup- after puberty, when epiphyses of the long bones have closed.
prelin), leuprolide (Lupron), nafarelin (Synarel), and trip- They are also used to treat short stature in children that is
torelin (Trelstar) are equivalent to gonadotropin-releasing associated with chronic renal failure or Turner syndrome
hormone. After initial stimulation of LH and FSH secretion, (a genetic disorder that occurs in girls). In adults, the drugs
chronic administration of therapeutic doses inhibits gona- may be used to treat deficiency states (eg, those caused by
dotropin secretion. This action results in decreased produc- disease, surgery, or radiation of the pituitary gland) or the tis-
tion of testosterone and estrogen, which is reversible when sue wasting associated with acquired immunodeficiency syn-
drug administration is stopped. In males, testosterone is re- drome. In general, dosage should be individualized according
duced to castrate levels. In premenopausal females, estrogens to response. Excessive administration can cause excessive
are reduced to postmenopausal levels. These effects occur growth (gigantism).
within 2 to 4 weeks after drug therapy is begun. In children Human chorionic gonadotropin (HCG; Chorex, others)
with central precocious puberty (CPP), gonadotropins (testos- produces physiologic effects similar to those of the naturally
terone in males, estrogen in females) are reduced to prepu- occurring LH. In males, it is used to evaluate the ability of
bertal levels. Leydigs cells to produce testosterone, to treat hypogonadism
The drugs cannot be given orally because they would be due to pituitary deficiency, and to treat cryptorchidism (un-
destroyed by enzymes in the GI tract. Most are given by in- descended testicle) in preadolescent boys. In women, HCG is
jection and are available in depot preparations that can be used in combination with menotropins to induce ovulation in
given once monthly or less often. Adverse effects are basi- the treatment of infertility. Excessive doses or prolonged ad-
cally those of testosterone or estrogen deficiency. When ministration can lead to sexual precocity, edema, and breast en-
given for prostate cancer, the drugs may cause increased largement caused by oversecretion of testosterone and estrogen.
bone pain and increased difficulty in urinating during the Menotropins (Pergonal), a gonadotropin preparation ob-
first few weeks of treatment. The drugs may also cause or tained from the urine of postmenopausal women, contains
aggravate depression. both FSH and LH. It is usually combined with HCG to in-
Octreotide (Sandostatin) has pharmacologic actions sim- duce ovulation in the treatment of infertility caused by lack
ilar to those of somatostatin. Indications for use include of pituitary gonadotropins.
acromegaly, in which it reduces blood levels of growth hor- Thyrotropin (Thytropar) is used as a diagnostic agent to
mone and insulin-like growth factor-1; carcinoid tumors, in distinguish between primary hypothyroidism (caused by a
which it inhibits diarrhea and flushing; and in vasoactive in- thyroid disorder) and secondary hypothyroidism (caused by
testinal peptide tumors, in which it relieves diarrhea (by de- pituitary malfunction). If thyroid hormones in serum are
creasing GI secretions and motility). It is also used to treat elevated after the administration of thyrotropin, then the hypo-
diarrhea in acquired immunodeficiency syndrome and other thyroidism is secondary to inadequate pituitary function.
conditions. The drug is most often given subcutaneously (SC) Thyrotropin must be used cautiously in clients with coronary
and may be self-administered. The long-acting formulation artery disease, congestive heart failure, or adrenocortical
(Sandostatin LAR Depot) must be given intramuscularly insufficiency. Thyrotropin alfa (Thyrogen) is a synthetic
(IM) in a gluteal muscle of the hip. Dosage should be reduced formulation of TSH used to treat thyroid cancer.
for older adults.
Hypothalamic Hormones
Gonadorelin (Factrel) Diagnostic test of gonadotropic SC, IV 100 mcg
functions of the anterior
pituitary
Goserelin (Zoladex) Endometriosis SC implant into upper abdominal
Metastatic breast cancer wall, 3.6 mg every 28 days or
Prostate cancer 10.8 mg every 3 months
Leuprolide (Lupron) Advanced prostatic cancer Endometriosis, uterine fibroids, CPP, SC 50 mcg/kg/d; IM Depot-
Central precocious puberty (CPP) IM depot injection, 3.75 mg Ped, weight 25 kg or less,
in children every mo or 11.25 every 3 mo 7.5 mg; >25 to 37.5 kg,
Endometriosis for 6 mo 11.25 mg; >37.5 kg, 15 mg
Uterine fibroid tumors Prostate cancer, SC 1 mg daily; every month
IM depot 7.5 mg every mo,
22.5 mg every 3 mo, or 30 mg
every 4 mo; implant (Viadur)
one (72 mg) every 12 mo
Nafarelin (Synarel) Endometriosis One spray (200 mcg) in one 2 sprays (400 mcg) in each
Central precocious puberty in nostril in the morning and one nostril morning and evening
children spray in the other nostril in the (1600 mcg/d), until resumption
evening (400 mcg/d), starting of puberty is desired
between the second and fourth
days of the menstrual cycle
Octreotide (Sandostatin) Acromegaly Acromegaly, SC 50100 mcg Dosage not established but
Carcinoid tumors three times daily 110 mcg/kg reportedly well
Vasoactive intestinal peptide Carcinoid tumors, SC 100 tolerated in young patients
tumors 600 mcg daily (average
Diarrhea 300 mcg) in 24 divided doses
Intestinal tumors, SC 200
300 mcg daily in 2 to 4 divided
doses
Diarrhea, IV, SC 50 mcg 2 or
3 times daily initially, then
adjusted according to response
Anterior Pituitary Hormones
Corticotropin Stimulate synthesis of hormones Therapeutic use, IM, SC 20 units
(ACTH, Acthar Gel) by the adrenal cortex four times daily
Diagnostic test of adrenal function Diagnostic use, IV infusion,
1025 units in 500 mL of 5%
dextrose or 0.9% sodium chlo-
ride solution, over 8 hours
Acthar Gel, IM 4080 units
q2472h
Cosyntropin Diagnostic test in suspected IM, IV 0.25 mg (equivalent to
(Cortrosyn) adrenal insufficiency 25 units ACTH)
Growth hormone: Promote growth in children whose Somatrem IM, up to 0.1 mg/kg
Somatrem (Protropin) growth is impaired by a defi- three times per week
Somatropin (Genotropin, ciency of endogenous growth Somatropin IM, up to 0.06 mg/kg
Humatrope, Nordotropin, hormone three times per week
Nutropin, Serostim)
Human chorionic Cryptorchidism Cryptorchidism and male hypo- Preadolescent boys: Cryp-
gonadotropin (HCG) Diagnostic test of testosterone gonadism, IM 5004000 units torchidism and hypogonadism,
(Chorex, Choron, Pregnyl) production 23 times per week for several IM 5004000 units 23 times
Choriogonadotropin alfa Induce ovulation in the treatment weeks per week for several weeks
(Ovidrel) of infertility To induce ovulation, IM To induce ovulation, IM
500010,000 units in one 500010,000 units in one
dose, 1 d after treatment with dose, 1 d after treatment with
menotropins menotropins
Menotropins (Pergonal) Combined with HCG to induce IM 1 ampule (75 units FSH and
ovulation in treatment of infertil- 75 units LH) daily for 912 d,
ity caused by lack of pituitary followed by HCG to induce
gonadotropins ovulation
(continued )
330 SECTION 4 DRUGS AFFECTING THE ENDOCRINE SYSTEM
Thyrotropin alfa (Thyrogen) Diagnostic test of thyroid function IM 0.9 mg every 24 h for 2 doses <16 y: Dosage not established
or every 72 h for 3 doses
Posterior Pituitary Hormones
Desmopressin Neurogenic diabetes insipidus Diabetes insipidus, intranasally 3 mo2 y: Diabetes insipidus,
(DDAVP, Stimate) Hemostasis (parenteral only) in 0.10.4 mL/d, usually in two intranasally 0.050.3 mL/d
spontaneous, trauma-induced divided doses in 12 doses
and perioperative bleeding Hemophilia A, von Willebrands Weight >10 kg: Hemophilia A,
disease, IV 0.3 mcg/kg in von Willebrands disease, same
50 mL sterile saline, infused as adult dosage
over 1530 min Weight 10 kg: Hemophilia A,
von Willebrands disease,
IV 0.3 mcg/kg in 10 mL of
sterile saline
Lypressin Diabetes insipidus Intranasal spray, one or two
sprays to one or both nostrils,
34 times per day
Vasopressin (Pitressin) Diabetes insipidus IM, SC, intranasally on cotton IM, SC, intranasally on cotton
pledgets, 0.250.5 mL pledgets, 0.1250.5 mL
(510 units) 23 times per day (2.510 units) 34 times
per day
Oxytocin (Pitocin) Induce labor Induction of labor, IV 1-mL ampule
Control postpartum bleeding (10 units) in 1000 mL of
5% dextrose injection
(10 units/1000 mL =
10 milliunits/mL), infused at
0.22 milliunits/min initially,
then regulated according to fre-
quency and strength of uterine
contractions
Prevention or treatment of post-
partum bleeding, IV 1040 units
in 1000 mL of 5% dextrose
injection, infused at 125 mL/h
(40 milliunits/min) or
0.61.8 units (0.06 0.18 mL)
diluted in 35 mL sodium chlo-
ride injection and injected
slowly; IM 0.31 mL
(310 units)
NURSING
ACTIONS Hypothalamic and Pituitary Hormones
1. Administer accurately
a. Read the manufacturers instructions and drug labels care- These hormone preparations are given infrequently and often re-
fully before drug preparation and administration. quire special techniques of administration.
2. Observe for therapeutic effects Therapeutic effects vary widely, depending on the particular pitu-
itary hormone given and the reason for use.
a. With gonadorelin and related drugs, observe for ovulation Therapeutic effects depend on the reason for use. Note that differ-
or decreased symptoms of endometriosis and absence of men- ent formulations are used to stimulate ovulation and treat endo-
struation. metriosis.
b. With corticotropin, therapeutic effects stem largely from Corticotropin is usually not recommended for the numerous non-
increased secretion of adrenal cortex hormones, especially the endocrine inflammatory disorders that respond to glucocorticoids.
glucocorticoids, and include anti-inflammatory effects (see Administration of glucocorticoids is more convenient and effec-
Chap. 24). tive than administration of corticotropin.
c. With chorionic gonadotropin and menotropins given in
cases of female infertility, ovulation and conception are thera-
peutic effects.
d. With chorionic gonadotropin given in cryptorchidism, the
therapeutic effect is descent of the testicles from the abdomen
to the scrotum.
e. With growth hormone, observe for increased skeletal growth Indicated by appropriate increases in height and weight.
and development.
f. With antidiuretics (desmopressin, lypressin, and vaso- These effects indicate control of diabetes insipidus.
pressin), observe for decreased urine output, increased urine
specific gravity, decreased signs of dehydration, decreased thirst.
g. With oxytocin given to induce labor, observe for the begin-
ning or the intensifying of uterine contractions.
h. With oxytocin given to control postpartum bleeding, ob-
serve for a firm uterine fundus and decreased vaginal bleeding.
i. With octreotide given for diarrhea, observe for decreased Octreotide is often used to control diarrhea associated with a
number and fluidity of stools. number of conditions.
3. Observe for adverse effects
a. With gonadorelin, observe for headache, nausea, light- Systemic reactions occur infrequently.
headedness, and local edema, pain and pruritus after subcuta-
neous injections.
b. With protirelin, observe for hypotension, nausea, headache, Although adverse effects occur in about 50% of patients, they are
lightheadedness, anxiety, drowsiness. usually minor and of short duration.
c. With corticotropin, observe for sodium and fluid retention, These adverse reactions are in general the same as those produced
edema, hypokalemia, hyperglycemia, osteoporosis, increased by adrenal cortex hormones. Severity of adverse reactions tends to
susceptibility to infection, myopathy, behavioral changes. increase with dosage and duration of corticotropin administration.
d. With human chorionic gonadotropin given to preadolescent Sexual precocity results from stimulation of excessive testosterone
boys, observe for sexual precocity, breast enlargement, and secretion at an early age.
edema.
e. With growth hormone, observe for mild edema, headache, Adverse effects are not common. Another adverse effect may be
localized muscle pain, weakness, hyperglycemia. development of antibodies to the drug, but this does not prevent its
growth-stimulating effects.
f. With menotropins, observe for symptoms of ovarian hyper- Adverse effects can be minimized by frequent pelvic examinations
stimulation, such as abdominal discomfort, weight gain, ascites, to check for ovarian enlargement and by laboratory measurement
pleural effusion, oliguria, and hypotension. of estrogen levels. Multiple gestation (mostly twins) is a possibil-
ity and is related to ovarian overstimulation.
(continued )
CHAPTER 23 HYPOTHALAMIC AND PITUITARY HORMONES 333
g. With desmopressin, observe for headache, nasal conges- Adverse reactions usually occur only with high dosages and tend
tion, nausea, and increase blood pressure. A more serious ad- to be relatively mild. Water intoxication (headache, nausea, vom-
verse reaction is water retention and hyponatremia. iting, confusion, lethargy, coma, convulsions) may occur with any
antidiuretic therapy if excessive fluids are ingested.
h. With lypressin, observe for headache and congestion of Adverse effects are usually mild and occur infrequently with usual
nasal passages, dyspnea and coughing (if the drug is inhaled), doses.
and water intoxication if excessive amounts of lypressin or
fluid are taken.
i. With vasopressin, observe for water intoxication; chest pain, With high doses, vasopressin constricts blood vessels, especially
myocardial infarction, increased blood pressure; abdominal coronary arteries, and stimulates smooth muscle of the gastro-
cramps, nausea, and diarrhea. intestinal tract. Special caution is necessary in clients with heart
disease, asthma, or epilepsy.
j. With oxytocin, observe for excessive stimulation or con- Severe adverse reactions are most likely to occur when oxytocin
tractility of the uterus, uterine rupture, and cervical and per- is given to induce labor and delivery.
ineal lacerations.
k. With octreotide, observe for arrhythmias, bradycardia, These are more common effects, especially in those receiving
diarrhea, headache, hyperglycemia, injection site pain, and octreotide for acromegaly.
symptoms of gallstones.
4. Observe for drug interactions
a. Drugs that increase effects of vasopressin:
General anesthetics, chlorpropamide (Diabinese) Potentiate vasopressin
b. Drug that decreases effects of vasopressin:
Lithium Inhibits the renal tubular reabsorption of water normally stimu-
lated by vasopressin
c. Drugs that increase effects of oxytocin:
(1) Estrogens With adequate estrogen levels, oxytocin increases uterine con-
tractility. When estrogen levels are low, the effect of oxytocin is
reduced.
(2) Vasoconstrictors or vasopressors (eg, ephedrine, epi- Severe, persistent hypertension with rupture of cerebral blood ves-
nephrine, norepinephrine) sels may occur because of additive vasoconstrictor effects. This is
a potentially lethal interaction and should be avoided.