Various Endocrine Glands of the Body

Types of Hormones

• Proteins, peptides and amino acid derivatives– Proteins are large molecules made of many

amino acids– Peptides are smaller molecules typically made

of a few amino acids– Amino acid derivatives are molecules derived

from a single amino acid

Lipid Hormones

• Steroid hormones– Derived from cholesterol– All similar in structure, but small differences

confer different effects– Similarities responsible for some cross

reactivity

• Eicosanoids– Derived from arachadonic acid (fat)

The hypothalamus

• Integrates information and many functions of the nervous system

• The hypothalamus controls the function of the pituitary gland in two ways

• It can secrete releasing hormones that act on the pituitary to stimulate secretion of stimulating hormones

• It can also stimulate the release of hormones from the posterior pituitary via nervous input

The Pituitary

• Divided into two halves

• The anterior portion is comprised of epithelial cells that act primarily as a glandular structure

• The posterior portion has extensive innervation and responds to nervous sytem input from the hypothalamus

The hypothalamus and the Pituitary

Table. 10.3a

Table. 10.3b

Hormones of the Pituitary• Growth hormone

– Controls growth and glucose metabolism

– Mediated via the somatomedins

• ACTH– Acts on the adrenal gland to stimulate the release of

cortisol

• Gonadotropins– Leutinizing hormone- ovulation, secretion of sex

hormones

– Follicle stimulating hormone – development of follicles and sperm cells

• Prolactin – stimulates breasts to develop milk

• Melanocyte stimulating hormone– Causes synthesis of melanin

Hormones of the Posterior Pituitary

• Antidiuretic hormone (aka vasopressin)– Causes the retention of fluid in the urine– Combats dehydration

• Oxytocin– Causes lactation– Contractions during child birth

The Thyroid Gland

• Secretes two hormones that regulate metabolic rate– Thyroxine (T4) – contains four iodine atoms– Triiodothyronine (T3) – contains three iiodine

atoms – Insufficient iodine impairs T3 and T4 synthesis

The Parathyroid Gland

• Primarily responsible for calcium homeostasis

• Parathyroid hormone– Causes increased production of vitamin D and

increased absorption of calcium in the intestine– Also causes resorption of calcium from the

bones– Increased retention of calcium in the kidneys

Regulation of the Thyroid Gland

Clinical Indication

Thyroid Hormones:

Replacement or supplement in hypothyroidism of any cause• cretinism- mental & physical retardation in• children with chronic untreated hypothyroidism• nontoxic goiter in adults• myxedema in adults

Thyroid HormonesHormones (proteins) secreted from the thyroidgland include:• Triiodothyronine (T3)• Thyroxine (T4)• and Thyrocalcitonin

TSH (Thyroid Stimulating Hormone)• Is secreted from the anterior pituitary gland in

response to changes in the blood levels of T3 and T4

• Triggers T3, T4 secretion from the thyroid gland

T3, T4- concerned with muscle and nerve tissue growth

• stimulates protein synthesis• increases the intestinal absorption of glucose• increases glycogen synthesis• mobilizes fatty acids• decreases serum cholesterol• increases BMR (basal metabolic rate)

Thyroid Hormones

Adverse Effects Related to Overdosing

Symptoms are dose and time dependent and characteristic of hyperthyroidism and increase in sympathetic tone:

• Mental confusion to psychotic behavior• Increased blood pressure• Increased heart rate • Diarrhea• Weight loss• Sweating• Menstrual irregularities• Tremors• Headache• Nervousness • Anginal episodes

Cautions and Contraindications

Thyroid hormone therapy

• is contraindicated in patients with myocardial infarction

• is not recommended for weight reduction in the management of obesity

• should be used with caution in patients – With cardiovascular disease, diabetes, adrenal

insufficiency– Who are elderly

Antithyroid Drugs

Clinical Indication

Treatment of hypersecretory conditions of

the thyroid in order to:

inactivate overactive tissue

inhibit production of T3 and T4

Effects of Hypersecretion or Hyperthyroidism

May be caused by tumors on the thyroid (thyrotoxic

crisis), pituitary, or hypothalamus

or

Autoimmune disease (Grave’s Disease) – LATS (long-acting thyroid stimulating protein) not the

same as TSH but same responses occur

Symptoms are dose and time dependent and

characteristic of hyperthyroidism especially increased

sympathetic autonomic tone

Antithyroid DrugsMechanism of action

Accumulate within the thyroid and destroy overactive tissue or inhibit the incorporation

of iodine for production of T3 and T4

• Radioactive Iodide (immediate onset)• Methimazone (requires time to see effect)• Propylthiouracil (requires time to see effect)

Antithyroid Drugs Special Considerations & Contraindications• Cross the placenta and affect fetal thyroid

development• Abrupt discontinuation of iodide may cause thyroid

storm• Iodide should be discontinued if fever, rash, soreness

in gums & teeth occur• Iodide-containing drugs are contraindicated in patients

with pulmonary edema• Radioactive iodide is present in the saliva and urine 24

hours after dosing

Calcium Homeostasis Parathyroid Hormones

Calcium ions

• Essential for neuromuscular and endocrine

function

• Serum levels strictly regulated by two polypeptide hormones– calcitonin (thyroid) – parathormone (parathyroid)

Calcium HomeostasisParathormone

Stimulated when serum calcium levels are low Stimulates bone resorption to mobilize calciumIncreases intestinal and renal reabsorption of calcium

Calcitonin Stimulated when serum calcium levels are highInhibits bone resorption

No effect on the intestine or kidneyAntagonizes parathormone

Calcium Disorders & Treatment• Hypocalcemia

Parathyroid damage during surgery

Treatment: calcium salts and vitamin D

• Hypercalcemia

Neoplasms, multiple myeloma, renal dysfunction

Treatment: diuretics to increase the renal clearance of calciumcalcitonin and bisphosphonates

Degenerative Bone Disease & Treatment

• OsteoporosisDecreased bone massDecreased mineral depositionIncreased bone resorptionTreatment: Bisphosphonates, estrogen

• Paget’s DiseaseHyperactive bone metabolismFragile bone and microfracturesTreatment: Calcitonin, bisphosphonates

Bisphosphonates

• Alendronate

• Etidronate

• Pamidronate

Poorly absorbed, not metabolized, excreted

in urine

The Adrenal Glands

• Adrenal medulla responsible for the hormonal fight or flight response

• Adrenal medulla releases epinephrine (adrenaline) and small amounts of norepinephrine

Fight or Flight Hormones

• Increases breakdown of glycogen to glucose in the liver

• Increase heart rate– Increases cardiac output to the tissues

• Increases blood pressure

• Increases metabolic rate in skeletal muscle, cardiac muscle and nervous tissue

The Adrenal Cortex

• Produces gluccocorticoids – Cortisol

• Regulates blood glucose levels

• Causes amino acids to be converted to glucose in the liver

• Cortisol secreted in times of stress to maintain glucose and energy levels

Clinical Indication

GlucocorticoidsReplacement therapy in adrenal insufficiency (Addison’s Disease)

Interrupt moderate to severe pain associated with conditions of inflammation

MineralocorticoidsReplacement therapy in adrenalectomy or adrenal tumors

Glucocorticoids• Adrenal cortex secretes glucocorticoids• Typically referred to as steroids• Regulate the metabolism of carbohydrates and

proteins• Demand for cortisol rises during stress and

tissue repair (e.g. wound healing)• Produce and conserve glucose• Promote protein catabolism and gluconeogenesis• Some mineralocorticoid activity i.e., sodium

retention

Corticosteroids Source of steroids-natural & synthetic

cortisone, hydrocortisone, prednisone, methylprenisolone, triamcinolone, betamethasone, dexamethasone

Vary in duration of action and potencyAntiinflammatory action

stabilize cell membranesprevent edema

Systemic use in patients with normal adrenal function arthritis, collagen disease, rheumatic disorders, respiratory disease, spinal cord injury

Topical use for skin irritation, rashes, itching

Corticosteroids Adverse Effects Associated with high doses and chronic use• Exaggeration of steroid symptoms of Cushing’s

diseasemood changesinsomniaweight gain, obesityprotein catabolism, muscle weakness, wastingosteoporosisdecreased wound healingincreased infections

fat deposition, moon facies

• Steroid addiction personality changes- “steroid psychosis”

psychological dependency (falacy)

Steroid Contraindications

• Patients with systemic fungal infections

• Local viral herpes infections

• Topical application to the eyes or orbital area

• Live virus vaccinations

The Pancreas

• The pancreas produces insulin and glucagon– The primary blood glucose regulatory

hormones

• Insulin produced in the beta cells of the islets of Langerhans

• Glucagon produced in the alpha cells

Insulin

• The primary glucoregulatory hormone

• Elevated in response to increased blood glucose or amino acids

• Inhibited when blood glucose is low

• Diabetes results from perturbed insulin metabolism

Diabetes

• Type 1- insulin dependent diabetes– The individual does not produce insulin

• Type II- non-insulin dependent diabetes mellitus (adult onset)– The individual does not respond appropriately

to insulin

Clinical Indication

Maintain circulating glucose levels sufficient to promote intracellular glucose transport and provide a source of energy for cells

Pancreatic Endocrine Function

The pancreas secrets two polypeptidehormones that regulate carbohydratemetabolism and blood glucose levels• Insulin

Promotes glucose movement into cells and carbohydrate storage

• GlucagonIncreases glucose in the blood by stimulatingglycogen breakdown

Insulin & Glucagon SecretionInsulin is secreted by beta cells in response to elevated glucose levels

• Mobilizes glucose into skeletal, heart, fat cells

• Promotes storage of fat and protein

Glucagon is secreted by alpha cells in response to low glucose levels

• Stimulates glyocogenolysis (breakdown)

• Mobilizes glucose into the circulation

• Defect in beta cell function

• Deficiency in insulin production and secretion

• Type I DM is insulin dependent (juvenile diabetes)genetic predisposition

• Type II DM relative insulin deficiency

(maturity-onset) aging, improper diet, obesity

Diabetes Mellitus (DM)

Diabetes Mellitus Symptoms • Persistently high blood glucose levels• Spill over into high urine glucose (glycosuria)• Volume of water excreted (polyuria)• Dehydration and thirst • Excessive fluid intake (polydipsia)• Excessive food intake (polyphagia)• Fat breakdown produces ketosis• Neuropathy, retinal hemorrhage• Renal dysfunction• Atherosclerosis

Treatment of Diabetes MellitusCorrect the metabolic imbalance with dietadjustment and administration of• Insulins• Oral sulfonylureas

acetohexamide, glipizide, glyburide, tolazamide, tolbutamide

• Glucose absorption inhibitorsacarbose, miglitol

• Antihyperglycemic drugsMetformin, troglitazone

Treatment of Diabetes MellitusInsulin (Type I, II DM)

• Sources: animal or recombinant DNA

• Onset of action varies with each insulin type

• Provides single peak of glucose activity

• Requires multiple daily doses

• Injected 15 to 30 minutes before meals

• Juice or sugar can reverse hypoglycemia

• Salicylates, beta-blockers, MAOI potentiate

insulin-induced hypoglycemia

Treatment of Diabetes MellitusOral sulfonylureas (oral hypoglycemics)• Type II DM only• Enter the beta cells and cause insulin release• Vary in onset and duration of action• Delay in onset related to absorption• Not a substitute for insulin• Prolonged action sustains hypoglycemia• Cause gastrointestinal irritation, nausea, diarrhea,

weakness, fatigue, dizziness,hypersensitivity reactions (rash), elevated serum liver enzymes, leukopenia, thrombocytopenia & anemia

Contraindications & Drug Interactions with Oral Hypoglycemics

Contraindicated in patients:• With a known hypersensitivity• With complications of fever, ketoacidosis or coma• With liver or renal disease, peptic ulcers• Who are pregnant

Drug Interactions occur because of• Protein binding displacement• Liver enzyme inhibition• Inhibition of glucose metabolism

Treatment of Diabetes Mellitus

Glucose Absorption Inhibitors• Do not reduce blood glucose levels• Do not release insulin• Interfere with dietary carbohydrate digestion• Delay a peak in glucose absorption after meals• Are ingested with meals• Do not impair liver enzymes• Cause flatulence, diarrhea, and abdominal pain• Contraindicated in patients with ketoacidosis, impaired

absorption, or hypersensitivity reaction

Treatment of Diabetes MellitusAntihyperglycemic Drugs• Do not reduce blood glucose levels or release insulin

• Keep glucose blood level from rising too fast• Decrease liver glucose production and intestinal glucose

absorption• Promote smoother distribution of glucose to tissues• Causes diarrhea, nausea, vomiting and flatulence• May cause lactic acidosis leading to respiratory and

cardiovascular distress• Contraindicated in patients with metabolic acidosis, renal

disease or abnormal creatinine clearance

The Testes and the Ovaries

• The testes produce testosterone

• The ovaries produce estrogen and progesterone

Clinical Indication

Female hormonesReplacement therapy in hypogonadism and menopause, or fertility enhancement, and adjunctive therapy for cancer

Prevent ovulation or implantation in the uterus

Alleviate menstrual disorders in nonmenopausal women

Female Sex HormonesEstrogens and Progestogens

LH and FSH secreted from the anterior pituitary gland induce conditions for the secretion of estrogen and progesterone

Estrogens secreted from developing cells in the ovaries stimulate• uterine lining and mammary glands• motility within the fallopian tubes• endometrium for implantation of a fertilized egg

Progesterone secreted from the corpus luteum• completes development uterine lining for implantation• stimulates mammary ducts for lactation

Pharmacological ActionsContraceptionEstrogen and progestogen combinations mimic the natural secretory cycle so that• FSH and LH secretions are suppressed• ovulation is blocked • cervical mucus is thickened decreasing the possibility of implantation

Hormone Replacement Therapy (HRT)Estrogens interact with receptors to reduce • hot flashes, sweating, muscle & joint aches that occur during menopause• bone resorption and turnover that decreases bone mineral density in osteoporosis• coronary artery disease by decreasing blood pressure, LDL- lipoproteins and insulin

Estrogen and ProgestogensAdverse Effects

• Nausea• Vomiting• Headache• Dizziness• Irritability• Depression• Fluid retention• Breast tenderness• Weight gain• Thrombophlebitis (pain in legs, groin)• Double-vision

Female Sex HormonesContraindicationsUse in pregnant women or those with a history of

ThrombophlebitisLiver diseaseBreast tumorsEstrogen-dependent cancersUndiagnosed vaginal bleeding

Special considerationsUse in women with a history of

DiabetesHigh blood pressureSeizure disorders

Male Sex Hormones - Androgens

Clinical IndicationIn menReplacement therapy in hypogonadism, delayed puberty, and impotence due to androgen deficiency

In womenAdjunctive therapy for inoperable breast cancer and postpartum breast engorgement

Androgens Pharmacologic Action

Anabolic action - Stimulate protein synthesisClinical benefit- Increase body weight and appetite

Nontherapeutic use- Increase muscle mass and enhance athletic performance

Erythropoiesis-Stimulate production of RBCs Clinical benefit- Reverse refractory anemia

Inhibit tumor growthClinical benefit- reduce pain & swelling in women with fibrocystic breast disease

Adverse Effects

Men may develop Women may develop• Decreased sperm count Hirsutism• Increased breast tissue Menstrual irregularities• Sustained erection Acne• Tumors Deepening voice• Addiction syndrome

Men and women• Jaundice• Nausea• Vomiting• Diarrhea • Retention of sodium and water

Result from chronic high dose use

Androgens Special Considerations and Contraindications

ContraindicationsMen breast or prostate cancerPregnant women- virilization of fetus

Special considerationsBlood glucose levels may fluctuate in diabetic patientsBruising and localized hemorrhages may increase in patients also receiving anticoagulants

ImpotenceInability to achieve or maintain an erection

Causes include• Nerve or spinal cord damage• Diminished blood flow to penis• Medication-induced reduction in nerve excitability

during sexual performance

TreatmentSildenafil (oral phosphodiesterase PDE inhibitor)Inhibits an enzyme (PDE) in muscle metabolismThat increases blood flow and rigidity in the penis

Sildenafil Adverse Effects

• Headache

• Flushing

• Nasal congestion

• Diarrhea

• Rash

• Upset stomach

Sildenafil Contraindications

• Patients taking nitrates may develop live-threatening hypotension and cardiovascular collapse

• Patients predisposed to sustained erection (e.g., sickle cell anemia, leukemia)