PHA 220 Pharmacology Chapter 29 The Endocrine System Made by Darell Connor CPhT.

PHA 220 Pharmacology Chapter 29 The Endocrine System

Made by Darell Connor CPhT

Anatomy and Physiology of the Endocrine System

• Endocrine System:– Internal “communication” system

that consists of:• hypothalamus• pituitary gland• Hormone producing glands

– thymus

– adrenal

– thyroid/parathyroid

– pancrease

– ovaries

– testies

– pineal

– These glands produce hormones to help regulate the body’s growth, metabolism, sexual development, and function


• Endocrine System cont.– Hypothalamus and the

pituitary gland are the major drivers of the endocrine system

• Pituitary Gland Controls:– Thyroid, parathyroid, pancreas,

adrenal glands, and gonads

• Hypothalamus– controls the activity of the

pituitary gland`


• Hormones:– a chemical substance

“messenger” to the cells through the bloodstream

• specific to cells to receive and respond to its message

– Steroids: “-one”• Slow and long acting

– Peptides and amines• proteins• fast acting and short lived• insulin/ADH

– Feedback control• depends on supply and demand


Anatomy and Physiology of the Endocrine System• Hypothalamus

– Functions: • Maintain homeostasis

– BP, Temperature, fluid and electrolyte balance, body weight

» Set points

• Control activity of the Pituitary gland

– Releases hormones called releasing factors

» stimulate the release of hormones that are produced in the anterior lobe called tropic hormones

» Tropic means growth (stimulating) control activities of other endocrine glands


• Hypothalamus cont.– produces oxytocin and Anti-

diuretic hormone (ADH)• stored in the posterior lobe of the

pituitary gland• Posterior lobe (neurohypophysis)

– Negative feedback• the mechanism that controls the

release of tropic hormones from the anterior pituitary gland

• Thyroid Stimulating Hormone– release the hormone thyroxine

– higher than normal thyroxine levels inhibits the release of TSH


• Hypothalamus cont.– Follicle stimulating hormone

(FSH)• released from the anterior pituitary

gland• stimulates the maturation of an

egg in the ovary• once the egg has matured, ovary

releases negative feedback to the hypothalamus

• hypothalamus inhibits the releasing factor stops sending FSH


• Thyroid Releasing Hormone– Stimulates thyroid-stimulating hormone (TSH)

• Corticotropin Releasing Hormone (CRH)– Stimulates adrenocorticotropin hormone (ACTH)

• Growth Hormone Releasing Hormone (GHRH)– Stimulates Growth hormone (GH)

• Somatostatin – Inhibits GH

• Gonadotropin Releasing Hormone (GNRH) – Stimulates both luteinizing hormone (LH) and follicle stimulating

hormone (FSH)

• All hormones stimulate a specific endocrine gland except GH/somatotropin


• Pituitary Gland– The anterior pituitary gland secretes hormones that regulate the

activities of the other endocrine glands


• TSH stimulates the thyroid gland• FSH/LH stimulate the gonads

– Gametogenesis and steroid production

• GH is sent to all body parts for linear growth and intermediate metabolism

• ACTH adrenal glandscause growth for the adrenal cortex and synthesis and secretion of cortisol

• Prolactin mammary glands produce milk during and after pregnancy

•


• Pituitary Gland cont.– Class of Pituitary hormones– Somatomammotrophs

• Somatotrophs: GH or somatotropin

• Mammotrophs: Lactotrops PRL

– Glycoproteins• Thyrotrophs: TSH or thyrotropin• Gonadotrophs: LH and FSH• Cortiotrophs: ACTH or

corticotropin• Pro-opiomelanocortin (POMC):

ACTH and LPH


• Thyroid and Parathyroid– Thyroid

• small gland located in front of the neck

• composed of 2 lobes• directly regulated by the anterior

pituitary gland and indirectly by the hypothalamus

• Contains two types of cells– Follicular cells: secrete

Thyroxine (T4) and triiodothyronine (T3)

– Parafollicular cells: secrete calcitonin


Thyroxine (T4) Triiodothyronine (T3)



• Thyroid and Parathyroid cont.– produces 80% T4 and 20% T3

• T3 is more potent than T4– Thyroid gland requires iodine in order to produce T3 and T4

• Richest source of iodine include: seafood and seaweed; Iodized Salt• Iodine + amino acid tyrosine = T3 and T4

– Released into the bloodstream transported to the whole body control metabolism

– Responsible for the enhancement of growth and development and for NS maturation in children

• Thermogenesis: T4 and T3 produce heat by increasing the body’s oxidative metabolism

– Synthesis of Na+/K+ ATPase• Growth/Development: T4 and T3 are essential for myelinatin and

development of the NS– Deficiency results in mental retardation– Overproduction: Restlessness and hypersensitivity

• Heart: Excess T4 and T3 increase heart stroke volume and HR by increasing the heart’s sensitivity to catecholamines



• Adrenal Glands– located on the upper part of

each kidney• Inner layer: Adrenal medulla

– Secretes EPI (SNS)

• Outer layer: Adrenal cortex

– Secretes 2 classes of corticosteroids (Adrenal Cortex)

• Glucocorticoids• Minteralocorticodes


• Adrenal Glands– Adrenocorticotropin (ACTH)

• Sleep-wake cycle: large amounts of adrenocorticotropin and cortisol are secreted while a person is awake

– Small amounts during sleep

– Cortisol requires body metabolism to meet requirements for wake period

• Stress: when the body is subjected to increased demands of physical or mental exertion

– Stress produces an increase of ACTH stimulates the Adrenal Gland increase secretion of Cortisol (increase the body’s ability to cope with the demands of stress

• Negative Feedback– Releasing factor + ACTH stimulate secretion and return of

Cortisol into the bloodstream



• Adrenal glands cont.– Glucocorticoids

• regulate the metabolis of carbohydrates and proteins, especially during stress

• Increase in stress = increase requirement for Glucose

• Wound healing = increase requirement for Glucose

• Inflammation is the first step in the process of wound healing

– Potent Anti-inflammatory effects

• Treat inflammatory and allergic conditions and have a longer duration of action


• Mineralcorticoids– main function and purpose is to regulate the electrolyte, or salt and fluid,

balance of the body• Maintains pH balance, prevent dehydration, assist in electrical functions and processes

in the body

– Aldosterone:• site of action is in the distal tubules of the nephrons • increases the reabsorption of Na+ ( returns to the blood supply) = exchange of K• H20 is reabsorbed with Na+

– isotonic


• Gonads– Gonadotropin releasing

hormone (GnRH)• released by the hypothalamus

that precipitates the onset of sexual maturity in both males and females

• needed for both sexual maturity and normal reproduction

• Stimulating the release of Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland

• LH and FSH stimulating the production of sex hormones in the gonads

– Development of sex organs and secondary sex characteristics


• Female Sex hormones– Estrogen and Progesterone

• Estrogen: is responsible for the development of secondary sex characteristics

– Inhibition of osteoclasts and bone loss

• Progesterone: prepares the lining of the uterus for the implantation of a fertilized egg

• Oxytocin: secreted by the posterior pituitary gland = stimulates the uterus to start contracting at the beginning of labor

• Prolactin: signals the mammary glands to start producing milk


• Male Sex Hormones– Androgens (masculinizing

hormones)– Testosterone: main male sex

hormone produces in the testes

• development of male sex organs and to maintain secondary sex characteristics

– Progesterone: produced in the adrenal gland and testes

• plays an integral part in maintaining a healthy prostate

HRT: Estrogen and Menopause• Estrogen

– After menopause, estrone is the most active estrogen

• Made in the adrenal glands only

– HRT: Prescribed for symptomatic Tx of Sx of menopause

• hot flashes, vaginal dryness, Osteoporosis, reduction in heart risks, painful uterine bleeding, vaginal or vuvlar atrophy

– Estrogen can reduce LDL and increase HDL

– Estrogen c Progesterone: Heart health and prevent bone fractures

HRT: Estrogen and Menopause• Risks of HRT: Estrogen

– Increase risk of liver disease• Increase the liver’s ability to

manufacture clotting factors• Risk when patients on Coumadin

– Clots: Side effect based on dosing

• Cigarette increases the chance of clots

– Buildup of the uterine lining (Enometrial hyperplasia) and Increase risk of endometrial carcinoma

• Progesterone c Estrogen reduce the chance of cancer

HRT: Estrogen and Menopause• Indications for HRT

Estrogen– Vasomotor symptoms

associated with menopause

– atrophic vaginitis– Kraurosis vulvae– female hypoganadism– hysterectomy– ovarian failure– breast cancer (palliative)– Prostatic carcinoma

• Contraindication– undiagnosed abdnormal

genital bleeding– history of cancer in the

breast– estorgen-dependent

neoplasia– DVT or pulmonary embolism– Arterial thromboembolic

disease– Liver dysfunction/disease– Sensitivity to estrogens– Pregnancy

HRT: Testosterone• HRT: Testosterone

– produces an anabolic effect that promotes the synthesis and retention of proteins, for muscle and bone, in the body

• Increase in Testosterone = easier for the body to build muscle and more muscle to be built; rebuild muscle tissue

– Promote weight gain especially after surgery

– Abuse of testosterone can cause irreversible effects

HRT: Testosterone• Indications for HRT

Testosterone– weight gain for chronic

nutritional deficiencies or wasting syndromes (AIDS/Chemo)

– relief of bone pain with Osteoporosis

– Corticosteroid induced catabolism

– Hereditary angioedema– Hypogonadism– Severe Antimetastic breast

cancer in women– Cryptorchidism

• Angioedema– autosomal-dominant

disorder characterized by recurring episodes of swelling of the face, extremities, genitalia, bowel wall, and Upper respiratory tract

• Deficiency/nonfunctional C1 esterase inhibitor

Side Effects of Anabolic Steroids

• Side effects– Increase in testosterone

and anabolic steroids = pituitary gland to stop producing gonadotropin

• Gonadotropin is necessary for spermatogenesis

– Domino effect• causing testicular atrophy,

decreased size and function of the testicles and testes, lowered sperm count, reversible sterility, Priapism, prostate enlargement, and frequent or continuing erections

• Possible permanent imbalance in hormone

Glandular Disease States• Cancer

– Breast, uterus, and prostate gland are dependent on the presence of sex hormones

– Use of sex hormones to antagonize or inhibit tumor growth

• Palliative only

• Breast Cancer– Estrogen feeds the cancer

cells• More Estrogen exogenously

causes more breast cancer, or enhances the growth of cancer that is already present

• Antiestrogenic Therapy will lower the amount of endogenous estrogen

Glandular Disease States• Breast Cancer cont.

– Androgens (progesterone) exert a protective influence, treat breast cancer in males

• Tamoxifen (anti-estrogen)– blocks Estrogen thus

slowing the growth and reproduction of breast cancer cells that depend on Estrogen

• Megestrol– Blocks the effect of androgen

on breast cancer cells

Glandular Disease States• Cancer cont.

– Polycystic Ovary Syndrome

• involves enlarged ovaries containing many fluid-filled sacs

• Females exhibit high levels of male hormones

• Testosterone exacerbate the problem

– Increase estrogen

Glandular Disease States• Prostate Cancer

– Small amounts of estrogen help reduce the amouont of bone loss caused by a common prostate cancer treatment

– Increase Levels of Estrogen, body doesn’t make as much testosterone so the cancer cannot feed on it.

• Estrogen actually block prostate cancer growth but only to a point

Endocrine System Disorders• Pituitary Gigantism

– results from excessive secretion of GH in childhood, and is usually caused by a nonmalignant tumor of the pituitary gland

• affects all areas

– Tx. surgical removal or radiation therapy of the pituitary gland

• Smoatostatin analogs = reduce secretion of GH

– Octerotide

– Lanreotide

• Dopamine Agonists – Bromocriptine

Endocrine System Disorders• Pituitary Dwarfism

– results from the lack of GH

– most cases, the child’s growth in height and weight are normal from 6-12 months of age

– Requires large amounts of exogenous GH

– Hypoglycemia may be present since GH is not present to counter insulin

– Patients may have an exaggerate “puppet/baby-doll “ face, proportionally short

– Caused by genetic mutations at the moment of conception

– TX Somatrem, Protropin, and Humatrope

Endocrine System Disorders• Acromegaly

– results from an excessive secretion of GH during the adult years

– Characterized by enlarged bones of the cheek, hands, fee, and jaws

• Predominant forehead and large nose

– Arms, legs, and hands are disproportionate to the body

– atrophy of muscles– curvature of the spine– Patients suffer from joint pain,

cardiovascular disease, HTN, insulin resistance, visual impairment

Diabetes• Diabetes

– 6.6% of the United States has diabetes and 1/3 are unaware of their serious medical conditions

– Diabetes Mellitus: is a disease in which the body does not produce or properly use insulin

• Insulin: hormone that is needed to convert sugar, starches, and other foods into to energy needed for daily life

• Cause is unknown– Genetics

– Environmental Factors

Diabetes cont.• Categories of Diabetes

– Type 1: results from the body’s inability/failure to produce insulin– Type 2: results from Insulin resistance: the body fails to properly

use the insulin it produces)– Gestational: affects about 4 % of pregnant women in the US– Pre-Diabetes: a condition in which a person’s glucose is higher

than normal but not high enough to be classified as Type 2

Diabetes cont.• Diabetes Sx:

– Polyuria– Polydipsia (excessive thirst)– Polyphagia (excessive

hunger)– Unusual weight loss– Increase Fatigue– Irritability– Blurry vision

• Type 2 Diabetes– prevention through diet and

exercise– High Risk: HTN,

hyperlipidemia, Cardiovascular diseases,Rx/Dx

Diabetes and Insulin• Insulin

– Categories of Insulin• Rapid acting insulin• short acting insulin• intermediate acting insulins• long acting insulin• ultra long acting insulin• insulin mixtures

– Delivery Systems• injection• Pens• Jet Injectors• External/internal insulin pump• transdermal insulin• Oral spray insulin (ineffective)• Inhaled Insulin(ineffective)

Diabetes and Insulin cont.

Diabetes and Insulin cont…• Diabetes Insipidus

– is a condition that results from a decrease in or hyposecretion of ADH

– Similar Sx as DM• Polyuria• Polydipsia• Pholyphagia

– Lack of ADH is caused by the kidneys that not concentrate urine well

• More Diluted urine = increase urination= increase fluid intake

– Causes of DI• hypothalamus does not make

enough ADH• Kidneys do not respond to ADH• Genetics and Rx induced

Diabetes and Insulin cont…• Tx for Diabetes Insipidus

– DDAVP Nasal Spray• stands for Deamino-Delta-D-

Arginine Vasopressin

• acts like ADH

Cushing’s Syndrome• Cushing’s Syndrome:

– Also known as hypercortisolism or hyperadrenocortism

– When the body is exposed to high levels of the hormone Cortisol for long periods of time

• Cortisol: maintains BP and cardiovascular function, reduce the body’s inflammatory response, balancing the effects of insulin in breaking down sugars for energy, regulating metabolism of proteins, carbohydrates, and fats ; and response to stress

Cushing’s Syndrome• Cushing’s Syndrome

– May occur during long-term or high stress situations,

– long term therapy with glucocorticoid hormones

– overproduction of natural cortisol

– affects 10-15 people out of 1 million each year

– Risk: depression, alcoholism, malnutrition, and panic disorders

– Sx: • upper body obesity• increased fat around neck• thinning arms and legs

Cushing’s Syndrome cont.• Sx of Cushing’s Syndrome

cont.– Irritability – anxiety– depression– Women

• excess hair growth on face and body

• irregular menstrual cycles• absence of menstrual cycles

– Men• decreased fertility• diminishing or absent libido

Cushing’s Syndrome cont.• Tx for Cushing’s

Syndrome– depends on the cause– Surgery to use synthetic

cortisol to maintain and balance the amount needed in the body

– Cortisol inhibitors• Miotane• Aminoglutethimide• metyrapone• trilostane• ketoconazole

Addison’s Disease• Hypocortisolism/chronic

adrenal insufficiency– the adrenal glands do not

produce enough of the hormone cortisol and in some causes, it underproduces aldosterone

– Characterized by:• weight loss• muscle weakness• fatigue• Low BP• darkening of the skin

Addison’s Disease cont• Addison’s Disease

– Causes• cortisol deficiency are due to a

lack of ACTH from gradual destruction of the adrenal cortex by the body’s immune system

• classified as an autoimmune disease

• long term use of glucocorticoids such as Prednisone

• tumor

– Exogenous cortisol sends negative feedback to the hypothalamus and to stop making releasing factor CRH

• no releasing factor = no ACTH

Addison’s Disease cont.• Sx of Addison’s Disease

– darkening of the skin (hyperpigmentation)

– penetrating pain in lower back, abdomen, legs

– Sever N/V/D– Dehydration– Low BP– Loss of conciousness

• Tx of Addison’s Disease– synthetic cortisol replacement

by hydrocortisone or fludrocortisone

Cretinism• Cogenital hypothyroidism

– caused by the lack of thyroid hormone secretion

– lack of iodine in the diet of pregnant mothers

– Result: mental retardation and dwarfism

– coarse dry skin– slightly swollen tongue

• Tx– Synthetic thyroid hormone

Grave’s Disease• Thyroid eye

disease/thyroid orbitopathy– characterized by proptosis

(protruding eye) and swollen and congested eye muscles

– autoimmune disease in which the immune cells attach moth the eye muscles and the thyroid = dysfunction in both

– Tx• depends on signs and symptoms• Lubricating eye drops• corticosteroids for inflammation

and optic nerve compression• Radiation therapy

PHA 220 Pharmacology Chapter 29 The Endocrine System Made by Darell Connor CPhT.

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