PHYSIOLOGY OF THE ENDOCRINE SYSTEM

Participates in the regulation of essentially all body activities

• Metabolism of nutrients and water
• Reproduction
• Growth & Development
• Adapting to changes in internal and external environments in order to maintain homeostasis

Major organs
• Hypothalamus
• Pituitary Gland
• Parathyroid Glands
• Pancreas
• Adrenal Glands
• Ovaries
• Testes

Functioning via Hormones

• Substances synthesized and secreted into body fluids by one group of cells
• Have physiologic effects on other body cells
• Act as chemical messengers to transmit information between body cells and organs

Hormone production by other tissues

• GI mucosa
o Gastrin—enterogastrin—secretin—cholecystokinin
o Important in digestive function
• Kidneys
o Erythropoietin
o Stimulates bone marrow production of RBC
• WBC
o Cytokines
o Messeengers amoung leukocytes in inflammatory & immune processes
• Various Tissues
o Prostaglandins & Leukotrienes
o Variety of physiologic functions
• Neoplasm
o Added source of hormone production normally produced by an organ / gland
o Hormone production in organs not normally involved in such production
 Lung tumors (corticotropin—ACTH; antidiuretic hormone—ADH; Parathyroid
hormone)
 Kidney tumors (parpthyroid hormone)
o General affect = increase in specific hormone production

Endocrine System / Nervous System Interactions

Closely connected, anatomically and physiologically—work in harmony to maintain homeostasis

• Nervous system regulates rapid muscular and sensory activities by secreting substances that act as
neurotransmitters, circulating hormones, and local hormones
• Endocrine system regulates slow metabolic activities by secreting hormones that control cellular
metabolism, transport of substances across cell membranes, and other functions (reproduction, growth &
development, secretion)

1
Main connecting link = Hypothalamus
• Responds to nervous system stimulation by producing hormones
• Secretion of almost all pituitary gland hormones is controlled by the hypothalamus
• Referred to as hypothalamic—pituitary—adrenocortical axis (functions as a negative feedback system)
o Nerve fibers from hypothalamus directly connect to posterior pituitary and induces secretion of
posterior pituitary hormones
o Hypothalamus secretes hormones (releasing and inhibitory factors)—regulate anterior pituitary
hormone secretion—which acts on target tissues—which in turn produce other hormones
(hypothalamic corticotropin releasing hormone stimulates the anterior pituitary to produce
corticotropin which stimulates the adrenal cortex to produce cortisol)

General Characteristics of Hormones

Hormones circulate thru the blood stream and reach all body cells
• Some affect all cells (growth & thyroid hormone)
• Some affect only specific target tissues (corticotropin stimulates only the adrenal cortex)
• Some hormones can affect different tissues (ovarian estrogen acts on—ovarian follicles to promote
maturation—endometrial lining of uterus to stimulate its growth & cyclic changes—breast tissue to
stimulate growth of milk ducts—hypothalamic-pituitary system to regulate its own secretion)
• Several hormones can affect a single tissue or function
• Several hormones are secreted in cyclic patterns (24-hour—ACTH & cortisol; 28 day menstral cycle—
estrogen & progestin)

Hormone Pharmacokinetics
• Protein-derived hormones are synthesized, stored, and released into bloodstream in response to a stimulus
• Most hormones are constantly present in the blood, but plasma concentrations vary according to:
o Body needs
o Rate of synthesis & release
o Rate of metabolism & excretion
• Most hormones circulate in the unbound free active form
• Other hormones are transported by carrier proteins (some drugs compete for protein binding sites;
therefore, more free hormone may be available = hormone effect enhancement
• Hormones are continuously inactivated via several mechanisms to prevent their accumulation and
excessive effects
o Water-soluble, protein derived hormones have a short duration of action and are inactivated by
enzymes mainly in liver & kidneys
o Lipid-soluble steroid & thyroid hormones have a longer duration of action—bound to plasma
proteins—once released they are conjugated in the liver into inactive forms & excreted in bile or
urine
o Some are inactivated by enzymes at receptor sites

Hormone Action at the Cellular Level

• Hormones modify cellular functions by binding with receptors in cell membranes or inside cells
• Major determinants of target cell response to hormone action is the number of receptors and their affinity
for the specific hormone
• The number of target organ receptors respond to availability of specific hormone
o Up-regulation = increase in receptor numbers when hormone levels are low
o Down-regulation = decrease in receptor numbers when hormone levels are high
• After binding—hormone-receptor complex—initiates intracellular biochemical reactions, depending on the
specific hormone and the type of cell

2
Hormonal Disorders
• Malfunction of endocrine organs associated with hyposecretion or hypersecretion of hormones
• Hypofunction
o Congenital defect resulting in absence of an endocrine gland, abnormally developed gland, or
absence of an enzyme required for glandular synthesis of a hormone
o Gland may be damaged or destroyed by impaired blood flow, infection or inflammation,
autoimmune disorders, or neoplasms
o Endocrine gland may atrophy and less capable of hormone production because of aging process,
drug therapy, disease, or for unknown reasons
o Endocrine gland may produce adequate hormones, but hormones may not be able to function
normally due to receptor defects
o Intracellular metabolic processes may not respond appropriately
• Hyperfunction
o Usually characterized by excessive hormone production
 Excessive stimulation and enlargement of endocrine gland
 Hormone-producing tumor of the gland
 Hormone-producing tumor of non-endocrine tissues

General Characteristics of Hormonal Drugs

• Include natural hormones from humans or animal sources and synthetic hormones (have a more potent and
prolonged effect)
• Given for
o Physiologic Effect
 Small doses as a replacement or substitute for amount usually secreted by a gland
(insulin;synthroid)
o Pharmacologic Effect
 Involves relatively large doses for effects greater than physiologic effects (adrenal
corticosteroids for anti-inflammatory effects)
• Powerful drugs that produce widespread therapeutic and adverse effects
• Administration of one hormone may alter effects of another hormone
• Hormonal drugs more often given for disorders resulting from hypofunction rather than hyperfunction of
endocrine hormones

3
 HYPOTHALAMIC & PITUITARY HORMONES

Hypothalamus & Pituitary interact to control most metabolic function and to maintain homeostasis
• Hypothalamus controls secretions of pituitary gland
• Pituitary gland regulates secretions of functions of other body organs and tissues (target tissues)
• Pituitary glands actually 2 glands, each with different structures and functions
o Anterior pituitary
 Different types of cellular types that synthesize and secrete different hormones
o Posterior pituitary
 Extension of hypothalamus and composed mainly of nerve fibers
 Does not produce hormones—stores and releases hormones produced by the
hypothalamus

Hypothalamic Hormones

Corticotropin-releasing Hormone or Factor (CRH or CRF)

• Causes release of Corticotropin in response to stress and threatening stimuli
• Secretion is influenced by several neurotransmitters
• Ability of CRH to stimulate corticotropin secretion is increased by vasopressin and decreased or prevented
by somatostatin and elevated levels of glucocorticoids
• CRH used in diagnosis of Cushing’s Disease (excess cortisol production)

Growth Hormone-releasing Hormone (GHRH)

• Causes release of Growth Hormone in response to low blood levels of the hormone
• GHRH also found in the pancreas
• Secretion of GHRH is influenced by several neurotransmitters
• Stimulatory effect of GHRH on Growth Hormone is blocked by somatostatin
• GHRH used to test pituitary function and to stimulate growth in children with GHRH deficiency

Growth Hormone Release-inhibiting Hormone (Somatostatin)

• Inhibits release of Growth Hormone
• Found in many tissues
• Secretion is stimulated by several neurotransmitters
• Somatostatin also inhibits other functions
o Secretion of corticotropin
o Secretion of thyroid-stimulating hormone
o Secretion of prolactin
o Secretion of pancreatic secretions
o Secretions of GI secretion
o Decreases GI motility, bile flow, and mesenteric blood flow
o Blocks action of GHRH
o Decreases thyrotropin-releasing hormone
• Somatostatin secretion is increased by growth hormone
• Long-acting somatostatin analog (octreotide—Sandostatin—used to treat acromegaly and TSH-secreting
pituitary tumors . New use GI irritation and bleeding

Thyrotropin-releasing Hormone (TRH)

• Causes release of thyroid-stimulating hormone in response to stress
• TRH used in tests of pituitary function and to diagnosis hyperthyroidism

Gonadotropin-releasing Hormone (GnRH)

• Causes release of follicle-stimulating hormone and luteinizing hormone

4
 • Important use in enhancing fertility

Prolactin-releasing Factor
• Stimulates release of prolactin during lactation after childbirth

Prolactin-inhibitory Factor (PIF)

• Inhibits release of prolactin at times other than lactation

Anterior Pituitary Hormones

Corticotropin (ACTH)
• Stimulates adrenal cortex to produce corticosteroids
• Negative feedback mechanism (Plasma levels of cortisol adequate—anterior pituitary does not release
ACTH)

Growth Hormone (Somatotropin)

• Stimulates growth of body tissues—promotes an increase in cell number and size
• Deficiency causes dwarfism in children
• Deficiency in adults causes numerous effects (most lead to alterations in CV health)
• Excessive secretion in preadolescent children leads to gigantism
• Excess in adulthood leads to acromegaly (distorted facial features and increased risk of DM & HTN)

Thyrotropin (TSH)
• Regulates secretion of thyroid hormones
• Negative feedback mechanism (Increased levels of thyroid hormones inhibits secretion of TSH by the
anterior pituitary and of TRH by the hypothalamus

FSH (Follicle-Stimulating Hormone)

• Stimulates functioning of sex glands (male & female)
• Drugs used to stimulate ovarian function in treatment of fertility

LH (interstitial cell-stimulating hormone) (Luteinizing Hormone)

• Stimulates hormone production by male & female gonads

Prolactin
• Secretion causes milk production during lactation

Melanocyte-stimulating Hormone
• Plays a role in skin pigmentation

Posterior Pituitary Hormones

Antidiuretic Hormone (ADH) (Vasopressin)

• Functions to regulate water balance
• ADH secretion—renal tubules more permeable to water—water reabsorption into plasma (water
conservation
o Secreted when body fluids become concentrated and when blood volume is low
• Absence of ADH—little water is reabsorbed (large amounts lost in the urine)
o SIADH—syndrome of inappropriate antidiuretic hormone

Oxytocin
• Functions in childbirth and lactation (initiates contractions of labor; causes milk to move from breast glands
to nipples)

5
INDIVIDUAL HORMONAL AGENTS
• Because hormones are protein, they must be given by injection or nasal inhalation (taken orally—destroyed
by GI proteolytic enzymes)

Hypothalamic Hormones

• Octreotide (Sandostatin)
o Parmacologic actions similar to those of somatostatin
o Indications for Use:
 Acromegaly
 Carcinoid tumors
 Vasoactive intestinal peptide tumors
 Diarrhea
o Adverse Effects:
 Dysrhythmias; Bradycardia; Headache; Hyperglycemia
 Symptoms of Gall Stones

Anterior Pituitary Hormones

• Menotropins (Pergonal)
o Indications for Use:
 Combined with HCG to induce ovulation in treatment of fertility caused by lack of
pituitary gonadotropins
o Adverse Effects:
 Symptoms of ovarian hyperstimulation, such as abdominal discomfort, weight gain,
ascites, pleural effusion, oliguria, & hypotension

• Thyrotropin (Thytropar)
o Used as a diagnostic agent to distinguish between primary hypothroidism (thyroid disorder) and
secondary hypothyroidism (pituitary malfunction)

• Thyrotropin alfa (Thyrogen)

o Synthetic formulation of TSH used to treat thyroid cancer

Posterior Pituitary Hormones

• Desmopressin (DDAVP)
o Indications for Use:
 Neurogenic diabetes insipidus (intranasal administration)
 Hemostasis (parenteral administration) in spontaneous, trauma-induced & perioperative
bleeding
o Adverse Effects:
 Headache; Nasal congestion; Nausea; Increased Bp
 Water retention & Hyponatremia (more serious adverse reaction)

• Vasopressin (Pitressin)
o Indications for Use:
 Diabetes insipidus
 First line agent in ACLS protocols (Pulseless V-tach; V-Fib)
o Adverse Effects:

6
  Water intoxication
 Chest pain; MI; Increased Bp
 Abdominal cramps; Nausea & diarrhea
o Drug-Drug Interactions
 Drugs that increase effects of vasopressin: general anesthetics; chlorpropramide
(Diabinese)
 Drugs that decrease effects of vasopressin: Lithium
• Oxytocin (Pitocin)
o Synthetic drug that exerts the same physiologic effects as the posterior pituitary hormone
o Indications for Use:
 Induce labor; Control postpartum bleeding
o Adverse effects:
 Excessvie stimulation or contractility of uterus; uterine rupture; cervival and perineal
lacerations
o Drug-Drug Interactions:
 Drugs that increase effects of oxytocin: Estrogens; vasoconstrictors or vasopressors

CORTICOSTEROIDS

• Also called glucocorticoids or steroids, and are produced by the adrenal cortex
• Affect almost all body organs—normal secretion important in homeostasis
• Disease results from inadequate or excessive secretion
• Exogenous corticosteroids are used in a number of disorders, but must be closely monitored as they
produce profound therapeutic and adverse effects

Endogenous Corticosteroids

• Adrenal cortex produces approximately 30 steroid hormones divided into:

o Glucocorticoids
o Mineralocorticoids
o Adrenal Sex Hormones
• All are derived from cholesterol and have similar chemical structures—but have different functions

Glucocorticoids
• Important in metabolic, inflammatory, and immune processes
• Include cortisol, corticosterone, and cortisone
• Created cyclically (largest amount in the morning and smallest amounts in the evening)

Mineralocorticoids
• Important in maintaining fluid & electrolyte balance
• Aldosterone is the main mineralocorticoid

Adrenal Sex Hormones

• Have little effects on normal body functioning
• Adrenal cortex secretes male androgens and female estrogens and progesterone
• Adrenal androgens are secreted continuously in both sexes.
o Increase protein synthesis (anabolism)—increases mass and strength of muscle & bone tissue
o Affect development of male secondary sex characteristics
o Increase hair growth and libido in women (excess secretion—hirustism, acne, breast atrophy,
deepening of the voice, & amenorrhea)
• Female sex hormones in excess may produce feminizing effects in men (breast enlargement, decreased hair
growth, voice changes)

7
Secretion of Corticosteroids
• Corticosteroid secretion—controlled by hypothalamus, anterior pituitary, and adrenal cortex
(hypothalamic-pituitary-adrenal (HPA) axis)
• Various stimuli (low plasma levels of corticosteroids, pain, anxiety, trauma, illness, anesthesia) activate the
system.
• Works on negative feedback mechanism, but this mechanism does not work well during stress responses
and negative feedback mechanism is overruled—can lead to body damage and dysfunction

Disorders of the Adrenal Cortex

• Involves increased or decreased production of corticosteroids, especially cortisol and aldosterone

Primary Adrenocortical Insufficiency (Addison’s Disease)

• Associated with destruction of the adrenal cortex by disorders such as tuberculosis, cancer, or hemorrhage
• Atrophy of adrenal gland caused by autoimmune disease, prolonged administration of exogenous
corticosteroids, and surgical excision of adrenal glands
• Inadequate production of cortisol and aldosterone

Secondary Adrenocortical Insufficiency

• Inadequate secretion of corticotropin, and most often caused by administration of corticosteroid drugs
• Mostly a glucocorticoid deficiency—mineralocorticoid secretion not significantly impaired

Congenital Adrenogenital Syndromes and Adrenal Hyperplasia

• Results from deficiencies in one or more enzymes required for cortisol production
• Low levels of cortisol lead to excessive corticotropin secretion—leads to excessive adrenal secretions of
androgens and hyperplasia

Androgen-Producing Tumors
• Usually benign—produce masculinizing effects

Adrenocortical Hyperfunction (Cushing’s Disease)

• Results from excessive corticotropin or a primary adrenal tumor which may be benign or malignant.
• Malignant tumors pften secrete several corticosteroids

Hyperaldosteronism
• Rare disorder caused by an adenoma or hyperplasia of the adrenal cortex cells that produce aldosterone
• Characterized by hypokalemia, hypernatremia, hypertension, thirst, and polyuria

Exogenous Corticosteroids (Glucocorticoid Drugs)

• Mainly given for replacement or therapeutic purposes
• Replacement—small doses to correct a deficiency state and to restore normal functioning
• Therapeutic—large doses to exert pharmacologic effect
• Most desired therapeutic effects are anti-inflammatory, immunosuppressive, antiallergic, and antistress
• Mineralocorticoid and androgenic effects are usually considered adverse reactions
• Additional characteristic of therapeutic corticsteroids
o All available as drug preparations, and many are synthetic so that their development increases
therapeutic effects while decreasing mineralocorticoid activity
o Drugs are palliative—treat symptoms but do not cure underlying disease. However, long term use
may produce serious adverse effects
o Drug effects vary, so a specific effect may be considered therapeutic in one client but an adverse
in another—In addition, some clients respond more favorably or experience adverse reactions
more readily than others taking equivalent doses (primarily due to rate of metabolism which can
vary in individuals)
o Administration of exogenous corticosteroids suppresses the HPA axis—results in atrophy of
adrenal cortex and decreased production of endogenous adrenal corticosteroids
o Hydrocortisone is the exogenous equivalent of endogenous cortisol—prototype drug

8
 o Anti-inflammatory activity of glucocorticoids is approximately equal when drugs are given in
equivalent doses
o Many glucocorticoids are available for use in different clinical problems, and routes of
administration vary

Mechanism of Action
• Drugs are lipid soluble and easily diffuse through cell membranes of target cells
• Effects differ based upon specific cell being targeted
• Multiple mechanisms of action including:
o Inhibiting arachidonic acid metabolism
o Strengthening or stabilizing biologic membranes
o Inhibiting the production of interlukin-1, tumor necrosis factor, and other cytokines
o Impairing phagocytosis
o Inpairing lymphocytes
o Inhibiting tissue repair

Indications for Use

• Used extensively to treat many different disorders in which inflammation may be a factor
o Allergic or hypersensitivity reactions
o Collagen disorders (systemic lupus erythematosus; scleroderma; periarteritis nodosa)
o Dermatologic disorders
o Endocrine disorders (adrenalcortical insufficiency and congenital adrenal hyperplasia)
o Gastrointestinal disorders (ulcerative colitis and regional enteritis—Chron’s disease)
o Hematologic Disorders (idiopathic thrombocytopenia purpura or acquired hemolytic anemia)
o Hepatic disorders (cirrhosis and ascites)
o Neoplastic disease (chronic leukemias; Hodgkin’s disease; other lymphomas; multiple myeloma)
o Neurologic conditions (cerebral edema; brain tumor; myasthenia gravis)
o Ophthalmic disorders (optic neuritis; sympathetic ophthalmia)
o Organ or tissue transplants and grafts
o Renal disorders (nephritic syndrome)
o Respiratory disorders (asthma; COPD; rhinitis)
o Rheumatic disorders (ankylosing spondylitis; acute and chronic bursitis; acute gouty arthritis;
rheumatoid arthritis; osteoarthritis)
o Shock (resulting from adrenocortical insufficiency (addisonian or adrenal crisis); also beneficial in
anaphylactic shock

Contraindications to Use
• Systemic fungal infections
• Those with hypersensitivities to drug formulations
• Use with caution in those:
o At risk for infection
o Clients with infections
o Diabetes mellitus
o Peptic ulcer disease
o Inflammatory bowel disorders
o Hypertension
o Congestive Heart failure
o Renal Insufficiency

EXOGENOUS CORTICOSTEROIDS (GLUCOCORTICOID DRUGS)

• Hydrocortisone (Prototype Drug)

9
 • Belclomethasone (Vanceril)-Iinhalation
• Budesonide (Pulmocort)--Inhalation
• Cortisone (Cortone)
• Dexamethasone (Decadron)
• Fluticasone (Flonase)--Inhalation
• Methylpresnisolone sodium (Solu-Medrol)
• Mometasone (Nasonex)--Inhalation
• Prednisone (Deltasone)
• Prednisolone sodium (Solu-Cortef)

CORTICOSTEROID DRUG SELECTION

• Adrenocortical Insufficiency
o Requires replacement of both glucocorticoids & mineralocorticoids
o Hydrocortisone & cortisone are usual drugs of choice

• Nonendocrine Disorders
o Antipinflammatory, antiallergic, antistres, & immunosuppressive effects
o Treat with drug of primarily glucocorticoid activity
o Prednisone is usual drug of choice

• Respiratory Disorders
o Use inhalation preparations
o Inhalation use replaces, prevents, delays, or decreases use of systemic drugs and thereby decreases
risks of serious adverse effects
o High doses however, may suppress adrenocortical function

• Cerebral Edema
o Associated with brain tumors, craniotomy, or head or spinal cord injury
o Dexamethasone (Decadrone) is usual drug of choice (penetrates blood-brain barrier more readily
& achieves higher concentratins in CSF & tissues); Also has minimal sodium- and water-retaining
properties (actually has a significant diuretic effect)

• Acute, life-Threatening Situations

o Usually IV use
o Hydrocortisone, dexamethasone, & methylprednisolone are used

PREVENTION OF ACUTE ADRENOCORTICAL INSUFFICIENCY

• Since suppression of HPA axis may occur with corticosteroid therapy and may lead to life threatening
inability to increase cortisol secretion when needed to cope with stress—tapering of drug doses is
absolutely necessary

• Strategies to minimize HPA suppression & risks of acute adrenal sufficiency

o Administer a systemic corticosteroid during high-stress situations (severe illness; traums; surgery)
to those who have received pharmacologic doses for 2 weeks within the previous year or who
receive long-term therapy (steroid dependent)
o Give short courses of systemic therapy for acute disorders (asthma attacks), & decrease dose or
stop dose within a few days
o Gradually taper dose of any systemic corticosteroid (higher doses & longer durations of therapy
require slow tapering)
o Use local rather than systemic therapy whenever possible (nasal or topical preparations)
o Use Alternate-day therapy (ADT)—involves titrating daily dose to lowest effective maintenance
level, then giving a double dose every other day

10
 THYROID AND ANTITHYROID DRUGS

• Thyroid Gland produces 3 hormones:

o Thyroxine (T4) T4 & T3 have same physiological effects
o Triiodothyronine (T3) More potent—rapid onset—shorter duration of action than T4
o Calcitonin Functions in calcium metabolism

• Production of T3 & T4 depends on presence of iodine from dietary sources, and from metabolic breakdown
of such iodine by thyroid enzymes into an inactive free iodine molecules.
• Free Iodine then binds with tyrosine to form T3 & T4—then stored in the chemically inactive thryroglobulin
molecule.

• Thyroid-stimulating hormone (thyrotropin or TSH) from the anterior pituitary stimulates the thyroid gland
to secrete the thyroid hormones which are released from the thryroglobulin molecule via enzymatic action
into a free active hormone form.

• After release, most of the thyroid hormones become bound to plasma proteins, and only small amounts
remain free as a biologically active form in the bloodstream.
• Once in cells the active thyroid hormones combine with cellular proteins, which are released slowly over
days to weeks in order for them to exert their target actions.

• Thyroid hormones control the rate of metabolism and therefore influence functioning of every cell in the
body.
• The heart, skeletal muscle, liver, and kidneys are especially responsive to the stimulating effects of thyroid
hormones
• Most physiologic effects include:
o Increased rate of cellular metabolism and oxygen consumption (increase in heat production)
o Increased heart rate, force of contraction, and cardiac output (increased cardiac workload)
o Increased carbohydrate metabolism
o Increased fat metabolism, including increased lipolytic effects of other hormones and metabolism
of cholesterol to bile acids
o Inhibition of pituitary secretion of TSH

Thyroid Disorders
• 3 thyroid disorders
o Goiter
o Hypothyroidism
o Hyperthyroidism

Simple Goiter
• Enlarged thyroid gland resulting from a deficiency of dietary iodine (TSH from anterior pituitary secreted
which causes thyroid gland to enlarge and produce more hormone)

11
• If thyroid gland is able to secrete adequate amounts of thyroid hormone, thyroid function remains normal
(goiter consequences—disfigurement, psychological distress, dyspnea, and dysphagia)
• Treatment involves giving iodine preparations and thyroid hormones to prevent further enlargement and
promote reduction in gland size. Surgical excision may be required.
• Simple goiter is uncommon in the US (iodized salt)
• If thyroid is unable to produce sufficient amounts of hormones—hypothroidism results

Hypothyroidism
• Primary Conditions
o Primary Hypothyroidism
o Secondary Hypothyroidism
o Congenital Hypothyroidism
o Adult Hypothyroidism

• Primary Hypothyroidism
o Disease or destruction of thyroid gland causes inadequate production of thyroid hormones
o Common causes:
 Chronic (Hashimoto’s) thyroiditis
 Autoimmune disorder
 Treatment of hyperthyroidism with antithyroid drugs, radiation therapy, or surgery
 Previous radiation to the thyroid gland area of the neck and treatment with amiodarone,
lithium, or iodine

• Secondary Hypothyroidism
o Caused by decreased TSH from anterior pituitary

• Congenital Hypothyroidism (Cretinism)

o Poorly functioning or no thyroid gland at birth
o May be due to inadequate maternal iodine intake
o Permanent mental retardation may occur

• Adult Hypothyroidism (Myxedema)

o Subclinical or clinical and occurs more often in women
o Subclinical (most common),
 Involves mildly elevated serum TSH and normal serum thyroxine (T4) levels and is
usually asyptomatic
o Clinical hypothyroidism
 Produces variable S&S, depending on circulating amounts of thyroid hormone
 Symptoms are initially mild and vague, then increase in incidence & severity over time as
thyroid gland atropies and functioning glandular tissue is replaced by fibrous connective
tissue
o Myxedema Coma
 Severe, life threatening hypothyroidism characterized by coma, hypothermia,
cardiovascular collapse, hypoventilation, and severe metabolic disorders such as
hyponatremia, hypoglycemia, and lactic acidosis
 Predisposing factors include exposure to cold, infection, trauma, respiratory disease, and
administration of CNS depressant drugs

• Treatment of Hypothroidism
o Replacement of thyroid hormones from exogenous sources
o Synthetic levothyroxine (Synthroid) is the drug of choice

Hyperthyroidism
• Characterized by excessive secretion of thyroid hormone

12
 • May be associated with Graves’s Disease, nodular goiter, thyroiditis, overtreatment with thyroid drugs,
functioning thyroid carcinoma, and pituitary adenoma that secretes excessive TSH
• Usually involves an enlarged thyroid gland that has an increased number of cells and an increased rate of
secretion--Results in a greatly increased rate of body metabolism
• Thyroid Storm (Thyrotoxic Crisis)—rare but severe complication characterized by extreme symptoms of
hyperthyroidism—S%S of severe tachycardia, fever, dehydration, heart failure, and coma

• Treatment of Hyperthyroidism
o Depends upon cause and can involve reduction of thyroid drugs, antithyroid drug therapy,
radioactive iodine, surgery, or a combination of methods

INDIVIDUAL THYROID & ANTITHYROID DRUGS

THYROID DRUGS (DRUGS USED IN HYPOTHYROIDISM)

• Levothyroxine (Synthroid)
o Synthetic preparation of T4
o Drug of choice for long-term treatment of hypothyroidism
o Most (99%) is bound to serum proteins
o Therapy is lifelong
o Do not switch from one brand to another (effects may be different)
o Adverse effects:
• Chest pain; heart palpitations; nervousness; insomnia
o Precautions:
• Stimulates the CNS & the heart—do not use with other drugs which may cause CNS or
cardiac stimulation (OTC cold remedies, etc.)
• Take on an empty stomach
• Do not take synthroid with an antacid, an iron preparation, or sulcrafate (Carafate)—
decreased absorption will occur

ANTITHYROID DRUGS (DRUGS USED IN HYPERTHYROIDISM)

• Prophythiouracil (PTU)
o Prototype antithyroid drug
o Does not interfere with release of thyroid hormones previously produced & stored—therapeutic
effects do not occur for several days to weeks

• Strong iodine solution (Lugol’s solution)

• Saturated solution of potassium iodide (SSKI)
o Both of these solutions can be used in short-term treatment of hyperthyroidism
o Lugol’s solution usually used to treat thyrotoxic crisis and to decrease the size and vascularity of
the thyroid gland before thyroidectomy
o SSKI is more often used as an expectorant but may be given as preparation for thyroidectomy

• Propranolol (Inderal)
o An beta-adrenergic blocking agent—not an antithyroid drug
o Used to control symptoms of hyperthyroidism resulting from sympathetic nervous system
stimulation (Used to treat dysrhythmias; excessive sweating; tremors; & nervousness)

13
 o Remember beta-adrenergic blocking agents can have adverse effects such as: hypotension; heart
failure; bronchoconstriction (contraindicated in those with asthma)

HORMONES THAT REGULATE CALCIUM AND BONE METABOLISM

• Calcium and bone metabolism regulated by 3 hormones

o Parathyroid Hormone (PTH)
o Calcitonin
o Vitamin D

• These hormones act to maintain normal serum levels of calcium

o When serum levels are reduced, hormonal mechanisms act to raise calcium levels
o When serum levels are increased, hormonal mechanisms act to lower calcium levels
• Overall, hormones alter
o Absorption of dietary calcium from GI tract
o Movement of calcium from bone to serum
o Excretion of calcium through the kidneys

• Disorders of calcium and bone metabolism include

o Hypocalcemia
o Hypercalcemia
o Osteoporosis
o Paget’s Disease
o Bone breakdown associated with breast cancer, some lung cancers, and multiple myeloma

• Drugs used to treat these conditions are those which alter serum calcium levels or to strengthen bone

Parathyroid Hormone (PTH)

• Secretion stimulated by low serum calcium and inhibited by normal or high levels (negative feedback
mechanism)
• Phosphate closely related to calcium in body functions—PTH also regulates phosphate metabolism
• In general, when serum calcium levels go up, phosphate levels go down, and visa versa
• Low serum calcium
o PTH raises level by acting on bone, intestines, and kidneys
o Bone breakdown is increased; increased absorption form intestines (PTH activates Vit D which
increases intestinal absorption); increased reabsorption of calcium in renal tubules
o Opposite effects of PTH on phosphate
• High serum calcium
o Decreased PTH secretion—opposite effects of low serum calcium level
• Disorders of parathyroid function

14
 o Hypoparathyroidism (deficient production of PTH)
 Often caused by removal of or damage to parathyroid gland during neck surgery
o Hyperparathyroidism (excessive production of PTH)
 Often caused by a tumor or hyperplasia of a parathyroid gland
 May also result from ectopic secretion of PTH by malignant tumors (carcinomas of lung,
pancreas, kidney, ovary, prostate gland, bladder)

Calcitonin
• Secretion controlled by the concentration of ionized calcium in the blood flowing through the thyroid gland
• When serum level of ionized calcium is increased, secretion of calcitonin is increased
• Calcitonin lowers serum calcium by decreasing movement of calcium from bone to serum and by
increasing urinary excretion of calcium

Vitamin D (Calciferol)
• Fat soluble vitamin that includes ergocalciferol (obtained from foods) and cholecalciferol (formed by
exposure to sunlight)
• Functions as a hormone and plays important role in calcium and bone metabolism
• Main action is to raise serum calcium levels by increasing intestinal absorption of calcium and mobilizing
calcium from bones
• Also promotes bone formation by providing adequate serum concentrations of minerals
• Vit D is not active, and must be converted to an active metabolite in the kidneys—PTH and adequate
hepatic and renal function are required to produce active metabolite
• Vit D deficiency causes inadequate absorption of calcium and phosphorus—low levels—stimulate PTH
secretion
o Children—results in rickets
o Adults—results in osteomalasia (decreased bone density and strength)

Calcium & Phosphorus

• Closely related physiologically
• Found in many of the same foods, and are absorbed together
• Both regulated by PTH and excreted by the kidneys
• Both required in cellular structure and function, and as calcium phosphate in the formation and
maintenance of bones & teeth

Bone Metabolism
• Role of bone in maintaining serum calcium levels takes precedence over its structural function (bone loss,
weakening and destruction will occur in order to maintain adequate serum calcium levels)
• Hormonal deficiencies, some diseases, and some medications (glucocorticoids) can also increase resorption
of calcium from bones—loss of bone mass and osteoporosis

Calcium & Bone Disorders

• Include Hypocalcemia & Hypercalcemia—both can be life threatening
• Drugs used act to raise or lower serum calcium levels in order to maintain homeostasis

DRUGS USED FOR CALCIUM & BONE DISORDERS

• Hypocalcemia & Osteoporosis

• Calcium & Vitamin D supplements & preparations
• Vitamin D agents:
o Calcitrol (Rocaltrol)
o Ergocalciferol (Calciferol)
• Parenteral Calcium agents:--Used for symptomatic hypocalcemia
o Calcium chloride
o Calcium gluconate

15
• Agents used for osteoporosis to inhibit bone breakdown & demineralization include:
o Bisphosphonates
 Aldendronate (Fosomax)—binds to bone—prevents calcium resorption from bone
 Risedronate (Actonel)—binds to bone—prevents calcium resorption from bone
 These drugs are poorly absorbed—must be taken on an empty stomach
o Calcitonin
 Calcitonin-salmon (Calcimar)
 Inhibits bone resorption
 Prevents further bone loss in the presence of adequaqt calcium & Vit D
 Helps to control pain in clients with osteoporosis or metastatic bone disease
o Estrogens & Antiestrogens
 Estrogen Replacement Therapy (ERT) beneficial in preventing postmenopausal
ostroporosis (most beneficial immediately after menopause—period of accelerated
bone loss)
 Antiestrogens
• Act like estrogens in some body tissues & prevent action of estrogen in
other body tissue
• Raloxifene (Evista)
o Approved for postmenopausal osteoporosis
• Tamoxifen (Nolvadex)
o Used to prevent & to treat breast cancer
o Has estrogenic effects & can be used to prevent osteoporosis & CV
disease, but is not approved to do so.

• Agents Used to Treat Hypercalcemia

o Biphosphonates
o Calcitonin
 Also used in Paget’s disease
 Most effective in hypercalcemia caused by hyperparathyroidism, prolonged
immobilization, or certain malignant neoplasms
 In acute hypercalcemia, very effective in lowering calcium levels in about 2 hours
o Corticosteroids
 Used to treat hypercalcemia due to malignancies or Vit D intoxication
 Hydrocortisone or prednisone often used (lowers calcium levels in 5-10 days)
o 0.9% NaCl IV infusion
 Treatment of choice for hypercalcemia
 Na inhibits reabsorption of calcium in renal tubules (increases urinary excretion)
 Several Liters are given daily
 Potassium & magnesium are also loss in the urine (monitor levels & replace as
needed)
o Furesomide (Lasix)
 Loop diuretic that increases calcium excretion in urine by preventing its reabsorption
by renal tubules
 Thiazide (hydrochlorothiazide) diuretics are contraindicated—they increase calcium
reabsorption
o Phosphate salts (Neutra-Phos)
 Inhibit intestinal absorption of calcium & increase deposition of calcium in bone
 Effective to treat hypercalcemia of any cause
 Potential adverse effect—calcification of soft tissues due to deposition of calcium
phosphate—can lead to severe impairment of kidney function
 Should only be given when hypercalcemia is accompanied by hypophosphatemia,
with normal renal function

16
17