The Endocrine System

• Consists of glands and other structures that produce hormones which are released into the circulatory system

The Endocrine System

• Consists of glands and other structures that produce hormones which are released into the circulatory system

• Regulation is established through hormones affecting target tissue

Regulation

• Homeostatsis is achieved through feedback mechanisms

• Negative feedback – negates change to bring levels back to normal

Pituitary Gland

• Regulates other endocrine glands as well as other body activities

Different hormones, different signals

Anteriorpituitary

Thyroidgland

TSHThyroidhormones

Negative feedback -

+

Hypo-thalamus

Waterabsorption

ADHosmolality

Negative feedback -

+

Pancreas

Liver, fat& muscle

InsulinGlucose

Negative feedback -

+

Para-thyroids

Bone, GIT& Kidney

PTHcalcium

Negative feedback -

+

Growth Hormone

• Non-endocrine related disorders can also cause growth delay:– Intrauterine growth retardation, chromosomal

defects, abnormal growth of cartilage or bone, poor nutrition, variety of systemic diseases

Growth Hormone

• Deficiency of endogenous growth hormone causes growth retardation

• Growth delay may be caused by– Family growth patterns, genetic disorders,

malnutrition, systemic or chronic illness, psychosocial stress, or a combination of these

– Endocrine deficiency, or problems with thyroxine, cortisol, insulin, or GH

Growth Hormone

• Release of GH is stimulated by the release of GHRF secreted by the hypothalamus

• GH is inhibited by – Glucocorticoids

– Obesity

– Depression

– Progesterone

– Hypokalemia

– Altered thyroid function

Synthetic Human Growth Hormones

• somatrem (Protropin)

• somatropin (Humatrope)

Drug List

Growth Hormone

• The younger the patient at time of treatment the greater the height that may be achieved

• Little response is seen after age 15-16 in boys and 14-15 in girls

Thyroid Gland

• Produces hormones (T3 and T4) that stimulate metabolic activity of body tissues

• Hypothalamus and pituitary glands work together to release TSH

• TSH stimulates T3 and T4 release

Thyroid Hormone Feedback Loop

• Thyroid hormones build up in the blood

• Signals are sent to the hypothalamic-pituitary axis that adequate levels have been met

• TSH levels decrease

Feedback

Anteriorpituitary

Thyroidgland

TSHThyroid

hormones

Negative feedback -

+

Hypothyroidism

• Production of thyroid hormones is below normal

• Cretinism occurs in children at birth due to inadequate maternal iodine intake– Can cause mental retardation, thick tongue,

lethargy, lack of response, short stature – can be corrected if treated

Primary and secondary disorders

PrimaryThyroiddisease

SecondaryThyroiddisease

Hypothyroidism Symptoms

• Apathy• Constipation• Decreased heart rate• Depression• Dry skin, nails, and

scalp• Easy fatiguing• Enlarged thyroid

• Lowered voice pitch• Myxedema• Puffy face• Reduced mental acuity• Swelling of eyelids• Tongue enlarged and

thickened• Weight gain

Causes of Hypothyroidism

• Autoimmune destruction of the gland

• Radioactive iodine therapy

• Surgical removal of the gland

Treatment for Hypothyroidism

• Thyroid replacement therapy– Should not be used to treat obesity

Agents for Hypothyroidism

• levothyroxine, T4 (Levothroid, Levoxyl, Synthroid)

• liothyronine, T3 (Cytomel)

• liotrix (Thyrolar)

• thyroid (Armour Thyroid)

Drug List

levothyroxine, T4 (Levothroid, Levoxyl, Synthroid)

• Used for chronic therapy

• Can be cardiotoxic

• Alters protein binding of other drugs

• Should not switch brands once stabilized

levothyroxine Dispensing Issues

• Can be cardiotoxic; report any of the following:– Chest pain, increased pulse, palpitations, heat

intolerance, excessive sweating

Warning!

levothyroxine Dispensing Issues

• Look-alike and Sound-alike Drugs:– levothyroxine (thyroid replacement)– levofloxacin (antibiotic)

Warning!

Hyperthyroidism

• Excessive thyroid hormone

• Most common cause is Grave’s disease

• Other causes:– Excessive exogenous iodine– Thyroid nodules– Tumor in the pituitary causing overproduction

of TSH

Symptoms of Hypterthyroidism

• Decreased menses• Diarrhea• Exophthalmos• Flushing of the skin• Heat intolerance• Nervousness• Perspiration• Tachycardia• Weight loss

Agents for Hyperthyroidism

• methimazole (Tapazole)

• propylthiouracil, PTU

• radioactive iodine, 131I

Drug List

Discussion

What are the treatment options for hyperthyroidism?

Discussion

What are the treatment options for hyperthyroidism?

Answer: in children: surgery and hormone replacement; adults: surgery or medications

Diabetes/Hypoglycemic Agents

• In the islets of Langerhans, in the pancreas, there are two primary specialized cells

• Alpha Cells

• Beta Cells

Hypoglycemic Agents

• In the islets of Langerhans, in the pancreas, there are two primary specialized cells

• Alpha Cells– Produce glucagon and raise blood glucose levels

• Beta Cells

Hypoglycemic Agents

• In the islets of Langerhans, in the pancreas, there are two primary specialized cells

• Alpha Cells– Produce glucagon and raise blood glucose levels

• Beta Cells– Produce insulin and lower blood glucose levels

Insulin

• Helps cells burn glucose for energy

• Works with receptors for glucose uptake

• Enhances transport and incorporation of amino acids into protein

• Increases ion transport into tissues

• Inhibits fat breakdown

Diabetes

• Caused by inadequate secretion or utilization of insulin

• Leads to excessive blood glucose levels

• Normal: 100 mg/dL

Type I Diabetes

• Occurs most commonly in children and young adults

• Average age of diagnosis is 11 or 12• Patients are insulin dependent and have no

ability to produce insulin on their own• May be due to an autoimmune response• Type I accounts for 5-10% of diabetic

population

Type II Diabetes

• Affect 80-90% of diabetics

• Most patients are over 40 and more women than men are affected

• Could be caused by insulin deficiency or insulin receptor resistance

• Many of these patients are overweight and can treat their diabetes with weight loss

Gestational Diabetes

• Occurs during pregnancy

• Increases risk of fetal morbidity and death

• Onset is during the 2nd and 3rd trimesters

• Can be treated with diet, exercise, and insulin

• 30-40% of women with gestational diabetes will develop type II in 5-10 years

Secondary Diabetes

• Caused by medications– Oral contraceptives– Beta blockers– Diuretics– Calcium channel blockers– Glucocorticoids– phenytoin

• May return to normal when drug is stopped

Symptoms of Diabetes

• Frequent infections• Glycosuria• Hunger• Increased urination and nocturia• Numbness and tingling• Slow wound healing• Thirst• Visual changes• Vomiting• Weight loss, easy fatigability, irritability, ketoacidosis

Complications of Diabetes

• Retinopathy leading to blindness

• Neuropathy

• Vascular problems can lead to inadequate healing which could lead to amputation

• Dermatologic involvement

• Nephropathy is the primary cause of end-stage renal disease

Lack of Insulin Activity

• Diabetics cannot use glucose therefore their bodies metabolize fat

• Gluconeogenesis is the formation of glucose from protein and fatty acids

• Fatty acid is oxidized into ketones

Ketones

• Strong acids

• Cause the body pH to drop

• Excreted in the urine or eliminated through respiration

• Causes a fruity acetone smell on the breath that can be mistaken for alcohol

Treating Diabetes

• Treatment consists of diet, exercise, and medications

• Blood glucose monitoring must be done regularly throughout the day

• Type II diabetics may be able to control the disease through diet and exercise alone

Treatment for Type II

1. Lifestyle changes

2. Oral monotherapy

3. Combination oral therapy

4. Oral drug plus insulin

5. Insulin only

General Treatment Guidelines

• Attention to diet• Blood pressure control• Compliance with

medications• Control of

hyperlipidemia• Daily foot inspections• Increased physical

activity

• Recognizing hypoglycemia

• Blood glucose testing• Monitoring in the Dr’s

office• Patient education• Prompt treatment of

infections• Setting goals

Drug for Lower Extremity Diabetic Ulcers

• becaplermin gel (Regranex)

Drug List

Insulin

• Administered subcutaneously due to degradation in the GI tract

• Different types of insulin have different onset of action times and duration of action times

Insulin Duration of Action

Type Duration of Action

Humalog, Novolog

1 hr (works in 15 mins and gone in about an hour)

Regular 5-6 hours (onset – 30 mins)

NPH 10-16 hours

Lente 12-18 hours

Lantus 24 hours

mixed Quick onset, longer duration

Insulin Dispensing Issues

• It is very easy to grab the wrong insulin in the refrigerator

• Always double-check yourself

• They look exactly alike

Warning!

Insulin administration sites should be rotated

Hypoglycemia

• Blood glucose levels of <70 mg/dL

• Can be caused by – Skipping meals– Too much exercise– Poor medication regimen– Certain drugs

Signs & Symptoms of Hypoglycemia

• Confusion• Double vision• Headache• Hunger• Numbness and

tingling in mouth and lips

• Nervousness• Palpitations• Sweating• Thirst• Visual disturbances• Weakness

Human Insulins

• NPH isophane insulin (Humulin N)

• insulin aspart (NovoLog)

• insulin glargine (Lantus)

• insulin lispro (Humalog)

• regular insulin (Humulin R)

Drug List

insulin lispro (Humalog)

• Rapid-onset insulin

• Can be injected immediately before or after meals

• May be used with a pump

insulin aspart (NovoLog)

• Rapid-acting insulin analog

• Each dose should be administered before meals

• May be used with a pump

insulin glargine (Lantus)

• Synthetic long-acting insulin

• Absorbed slowly and works over a 24-hour time period

• Works similarly to physiologic insulin release

Human InsulinsMixtures

• insulin aspart w/ protamine-insulin aspart (NovoLog Mix 70/30)

• insulin lispro w/ protamine-insulin lispro (Humalog Mix 75/25)

• insulin with zinc (lente) (Humulin L)• NPH-regular insulin (Humulin 70/30)

Drug List

Oral Hypoglycemic Agents First- Generation

Sulfonylureas

• chlorpropamide (Diabinese)

• tolbutamide

Drug List

Oral Hypoglycemic AgentsSecond-Generation

Sulfonylureas

• glimepiride (Amaryl)

• glipizide (Glucotrol, Glucotrol XL)

• glyburide (DiaBeta, Glynase, Micronase)

Drug List

glipizide (Glucotrol, Glucotrol XL)

• Taken with breakfast

• Promotes insulin release from beta cells

• Increases insulin sensitivity

glipizide Dispensing Issues

• Look-Alike and Sound-Alike Drugs– Glucotrol – Glucotrol XL

Warning!

glipizide Dispensing Issues

• Look-Alike and Sound-Alike Drugs– glipizide (Glucotrol, Glucotrol XL)– glyburide (DiaBeta, Glynase, Micronase)

Warning!

Oral Hypoglycemic Agents

Enzyme inhibitors:

• acarbose (Precose)

• miglitol (Glyset)

Biguanide:

• metformin (Glucophage, Riomet)

Drug List

metformin (Glucophage, Riomet)

• Decreases intestinal absorption of glucose and improves insulin sensitivity

• Has an effect on serum lipid levels

• Best candidates are overweight diabetics with high lipid profile

Oral Hypoglycemic Agents Glitazones/Thiazolidinediones

• pioglitazone (Actos)

• rosiglitazone (Avandia)

Drug List

pioglitazone (Actos)

• Depends on the presence of insulin

• Liver enzymes should be carefully monitored

• May be taken without regard to food

rosiglitazone (Avandia)

• Increases insulin sensitivity in muscle and adipose tissue

• Can be taken without regard to food

Oral Hypoglycemic Agents

Meglitinides

• nateglinide (Starlix)

• repaglinide (Prandin)

Drug List

Oral Hypoglycemic Agents Combinations

• glipizide-metformin (Metaglip)

• glyburide-metformin (Glucovance)

• rosiglitazone-metformin (Avandamet)

Drug List

Discussion

What does a diabetic have to be concerned with in relation to diet?

Discussion

What does a diabetic have to be concerned with in relation to diet?

Answer: Eating at the same time everyday; to limit sugar intake by reading package labels