Endocrine Pathophysiology




Endocrine system

Endocrine system is composed of glands, which secrete chemicals called hormones.
The hormones affect multiple target tissues and organs in the body.
Hormones regulate growth, fluid and electrolytes, energy, sexual maturation, reproduction and stress response.

Disorders are caused by insufficient hormones (Hypofunction), most common
Or excessive hormones (Hyperfunction)
Endocrine system... seesaw which can go up and down creating a problem with homeostasis.

Primary (the affected gland doesn’t work),
Secondary (the pituitary inadequately stimulates the target gland)
Tertiary (the hypothalamus is the cause of the problem).

The endocrine system is closely linked to the central nervous system (CNS).

Glands in endocrine system:
Hypothalmus
Adrenal
Pituitary
Pineal
Pancreatic islets
Parathyroid
Thyroid
Thymus
Ovaries and testes.

Most have clear roles except the pineal and the thymus gland.

Curiously, the pineal gland is about the size of a raisin and usually calcified by age 12. It is thought that it may have some something to do with melatonin production while the thymus is generally thought to be part of the immune system.

*The production and secretion of hormones is controlled by a negative feedback system.*

Intro to the Endocrine System: Basic overview of hormones and the endocrine system


Endocrine disorders

Type 1 Diabetes

Incidence/etiology -
Idiopathic or autoimmune destruction of pancreatic beta cells
Genetic predisposition and environmental factors may contribute
More prevalent in caucasians

Pathophysiology
Autoimmune destruction results in inadequate insulin secretion
10-20% of normal produces symptoms
Insulin is not able to help transport glucose across the cell membrane = hyperglycemia
Low insulin = hepatic glucose increase, hyperlipidemia, ketones
Growth hormone, cortisone, glucagon increase, which promote insulin resistance
Glycogenesis - glycogen from non-carbohydrate sources
Proteolysis - protein breakdown
Lipolysis - fat breakdown
Remember insulin is the KEY needed to enter the cells, no keys, no entry into the house of the cell!!!!

Blood glucose levels > 150-180mg/dl filtered out of blood and into urine
Insulin deficit
Decreased transportation and usage of glucose
Hyperglycemia
Glucosuria - Excess glucose spills in urine
Polyuria - glucose in urine creates a shift with additional water excreted, Na+, K+
Fluid loss through urine, high glucose levels draws fluid from cells
Polydipsia - Fluid loss, dehydration, creates thirst
Polyphagia – Lack of nutrients entering the cells stimulates appetite
Catabolism of fats and proteins > ketones due to lack of glucose in cells
Ketones are acid bodies buffered by bicarbonate, as bicarb is depleted metabolic acidosis increases
Kussmaul breathing slow deep breathing with acetone breath odor

Clinical Manifestations Type 1:
Polyuria
Polyphagia
Polydipsia
Weight loss
Dehydration
Occasionally, abdominal pain, vomiting
Irritability/fatigue
Diabetic ketoacidosis (DKA)

Diagnosis:
Presentation characteristics
3 P's and glucose >200 mg/dl
Or in diabetic ketoacidosis (DKA)
Oral glucose tolerance test (OGTT)
Fasting serum glucose
Fasting plasma glucose preferred
*A1c not recommended for diagnosis/for compliance 7% soon 6%

Type 2 Diabetes
Prevalent among children now
Contributing factors food consumption patterns
Lack of exercise
Obesity
Higher in AA, Hispanic, Asian or American Indian descent
90% have acanthosis skin condition with hyperpigmented patches in creases

Pathophysiology Type 2 diabetes
Social, environmental, behavioral contributors
Initially insulin resistance then beta cell failure

Clinical Manifestations:
Body mass index over 95%
Fatigue
Frequent infections

Diagnosis for type 2 = Fasting glucose >126 or random glucose >200 mg/dl

Treatment:
Education and prevention

Glucose Insulin and Diabetes: The basics of Type I and Type II diabetes


Parathyroid and calcium
Hypoparathyroidism:
Rare
May result from congenital disorders (DiGeorge Syndrome), surgical removal of parathyroids, destruction of parathyroid from Wilson's disease, hemachromatosis or medications.

Signs and Symptoms:
Life threatening hypocalcemia (tetany and convulsions)
Hyperirritability, muscle rigidity, seizures, vomiting, abdominal distention, apnea episodes, intermittent cyanosis
Muscle pain, cramps
Positive Chvostek sign (spasm of facial muscles after tapping facial nerve)
Positive Trousseau's sign

Hypocalcemia - Positive Chvostek and Trousseau's signs

Hyperparathyroidism:
Rare
Result of adenoma
Secondary to kidney disease (unable to reabsorb calcium)

Signs and symptoms:
Bone pain
Kidney stones
Pathologic bone fractures
Hypercalcemia - muscle weakness, peptic ulcer disease, fatigue, volume displacement, mental disturbance
Diagnosed by elevated serum calcium and elevated parathyroid hormone (PTH)

Pituitary hormones
Disorders of the pituitary:
The pituitary is often called the ‘master’ gland.
It has an anterior and posterior lobe.

The anterior pituitary produces growth hormone (GH), luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), and prolactin hormone (PL).

Disorders of the anterior pituitary:
Growth hormone deficiencies
Gigantism – excess growth hormone before puberty
Acromegaly – excess growth hormone in adult, usually by adenoma
Enlarged hands and feet
Protruding mandible or jaw
Results in glucose metabolism, eventual diabetes
Hypertension and cardiovascular disease




The posterior pituitary produces oxytocin and stores arginine vasopressin or antidiuretic hormone (ADH), which is produced in the hypothalamus. The anterior lobe of the pituitary regulates growth, sexual development/reproduction and metabolic activity.

žDisorders are related to a deficiency or excess of vasopressin or antidiuretic hormone (ADH)




























Diabetes insipidus:
A deficiency of antidiuretic hormone (ADH)
Mnemonic - I want a sip of water!

žDisorder of water regulation
žADH is suppose to concentrate the urine by stimulating reabsorption of water in the renal collecting tubules…anti (no) diuretic (urine)
ž*When this does not happen there are large amounts of diluted urine
žOften seen with head trauma, cranial surgery or surgery in the pituitary region, infection, or genetics
žMay be transient or permanent

Manifestations:
ž
Polyuria, polydipsia, enuresis
žCan have output from a few to 18 liters of urine a day, that's nine 2 liter coke bottles a day!

Treatment:
žReplacement therapy for ADH

Syndrome of Inappropriate Antidiuretic Hormone (SIADH):

While Diabetes Insipidus involves too little antidiuretic hormone (ADH), SIADH results from too much ADH.
This can be caused by infections, tumors, trauma, pulmonary disorders or chemotherapy
Mnemonic - See I Am Drowning Here ...too much water!


Excessive ADH leads to too much water retention; this leads to water intoxication
Water intoxication = hyponatremia, edema, elevated blood pressure, distended jugular veins, lung crackles,
weight gain, fluid and electrolyte imbalance, decreased urine output

Treatment includes:
Fluid management
Medications
Treatment of the causative factors

Thyroid
Goiter: enlargement of the thyroid gland due to hyper or hypo
Can interfere with esophagus, swallowing and compress trachea

Thyroid hormones
Congenital hypothyroidism (CH)
Low concentrations of circulating thyroid hormones T3, T4
Early detection prevents cretinism
TSH surges in first 24-48 hours so best to test after.
Newborn screening tests


Clinical Manifestations, mild hypothyroidism:
Pallor
Hypothermia, cold intolerance
Hypotonia, hypoactivity
Delayed mental responsiveness
Cool, dry, scaly skin
Low T3, T4
Low metabolic rate, weight gain
Bradycardia

Acquired Hypothyroidism:
Myxedema
Primary, secondary or tertiary
Primary caused by autoimmune chronic lymphocytic thyroiditis (Hashimoto's thyroiditis)
Secondary and tertiary are related to pituitary or hypothalmic dysfunction

Pathophysiology:
Antibodies are developed against thyroid gland, it becomes inflamed and destroyed
T4 levels decrease and TSH increases
Hashimoto’s thyroiditis – autoimmune disorder

Myxedema
Non-pitting edema, facial puffiness
Thick tongue
Myxedema coma – hypotension, hypoglycemia, hypothermia, loss of consciousness

Treatment:
Thyroid replacement - L-thyroxine (synthroid)
Goal to keep T4 in upper half and TSH in normal range
Lifelong replacement necessary
Diagnosis:
TSH, T4, free T4, Confirmation of thyroiditis with serum thyroid antibodies

Treatment:
Replacing thyroid hormone with L-thyroxine doasge based on weight
*Must be careful may experience side effects of hyperthyroidism if restoration too rapid*
Symptoms of hyperthyroidism > agressive behavior, increased intracranial pressure
So small dose and titrate up to euthyroid

Hyperthyroidism:
Graves disease
^ T3, ^ T4
Autoimmune factor
Women >30
Hypermetabolism
Toxic goiter
Exophthalmos protruding, staring eyes

Thyroid storm
Hyperthermia
Tachycardia
Heart failure
Delirium

Pathophysiology:
Antibodies formed against antigens in the thyroid gland, orbital tissue and dermis
Antibodies mimic action of TSH causing gland to inappropriately produce thyroid hormone
Goiter present

Diagnosis:
Serum thyroid tests
TSH suppressed
T3, T4 elevated

Treatment:
Difficult, chronic
Anti-thyroid medication - propylthiouracil (PTU), methimazole (MTZ, Tapazole), blocks synthesis of T3, T4
11-22% have side effects must be discontinued (rash, leukopenia, arthalgia, hair loss, lupus-like symptoms, hepatitis)

Beta-adrenergic blockers propranolol (Inderal) relieve tachycardia, restlessness, tremors

Radioactive iodine therapy (RAI) for over 15 years, tissue destruction in 6-18 weeks, hypothyroidism may occur

Thyroidectomy - noncompliant caregiver or failed other options
Spontaneous remission may occur 25%

Adrenal glands

Cushing Disease (Adenocortical Hyperfunction)
Cushing's Disease is adding a cushion of glucocorticords, cushions are fluffy and provide excess weight
Excess glucocorticoids (especially cortisol) in the bloodstream
Caused by a malignant carcinoma or hyperplasia of the adrenal glands or a benign tumor
Mnemonic trick - Cushings = Cushion, excess weight

Clinical Manifestations/Symptoms include:
Reduced linear growth
Mental or behavioral problems
Cushingoid appearance - moon face, fat pads on the shoulders and back
(most of the time the appearance is due to consumption of steroids for other reasons)
Muscle, capillary weakness, fatigue due to catabolism of protein
Demineralization of bones, osteoporosis due to decreased absorption of calcium
Excessive weight gain due to increased appetite
Increased blood pressure and blood volume due to salt retention


*If the adrenal glands are removed, hydrocortisone (Solu-Cortef, Cortisone acetate) is administered. Administration pattern best mimics the body to administer early in the morning. If the pt. is vomiting and cannot take the medication orally give injection or could lead to severe illness or Cardiovascular collapse.


Addison's Disease (Adrenal Insufficiency)
Remember 'Add'ison's Disease is really a subtraction problem! Minus adequate gluco and mineralocorticords!
Deficiency of glucocorticoids, mineralocorticords (aldosterone) and adrenal androgens
This affects the bodies ability to handle stress
Caused by autoimmune reponse , metabolic disease, infection or malignancy
Develops slowly
Early signs - weakness, fatigue, emotional lability, anorexia, salt craving, poor weight gain
Hyperpigmentation
Abdominal pain, nausea, vomiting, diarrhea, hypoglycemia
After a stressful event adrenal crisis may occur

Diagnostic tests:
Cortisol and urinary 17-hydroxycorticoid measured in am
ATCH stimulation test

Treatment and Nursing Management:
Replacement of hormones
Parental education
Management of an adrenal crisis

























































References:

Gould, B. E., & Dyer, R. M. (2011). Pathophysiology for the health professions (4 ed.). St. Louis, Missouri: Saunders Elsevier.


Story, L. (2012). Pathophysiology: A practical approach. Sudbury, MA: Jones & Bartlett Learning .

Videos:

Endocrine system
http://youtu.be/-S_vQZDH9hY

Acromegaly
http://www.youtube.com/watch?v=AX48MPIDyYw&feature=share&list=PLyrvqEUNOP3kLe6fEOJwg3FVu5vPRPDze

ADH
http://youtu.be/8dQdfbE8k