3- Endocrine Phys & Pathology

The endocrine system consists of

cells, tissues, and organs that secrete hormones

-Glands

-Discrete clusters of cells

-Individual cells

Hormones are

Chemicals produced by the body that have a specific regulatory effect on a target cell or organ

Endocrine glands characteristics

• Absence of ducts: Hormones released into the bloodstream

• Abundant blood supply

• Mostly consist of parenchymal cells: Minimal connective tissue

Endocrine chemical signaling

hormone is carried a long distance

via blood

Paracrine chemical signaling

Autocrine chemical signaling

Hormones are released in response to

an alteration in the cellular environment

- To maintain a regulated level of certain substances or

hormones secreted from other glands

Negative feedback of hormone

hormone inhibits further secretion of itself

• Glucose —> insulin and glucagon

• TSH —> T3 and T4

Positive feedback of hormone

effects of the hormone results in further hormone secretion

• Prolactin —> breast milk production

Feed forward control

anticipatory mechanism

• Glucagon-like peptide-1 (GLP-1) secreted from the

enteroendocrine cells in the small intestine to signal release of insulin before the digested glucose is absorbed in the blood

Describe up-regulation vs down regulation

-Up-regulation: increase in the number of receptors with

increase in hormone concentration

-Down-regulation: decrease in the number of receptors with

increase in hormone concentration

Hormone effect is both direct and indirect, describe both

-Direct effects: bind to intracellular hormone receptors and

modulate gene transcription

-Indirect effects: bind to cell surface receptors and stimulate signaling pathways

Which of the following types of regulation is an

anticipatory mechanism?

A. Positive feedback

B. Negative feedback

C. Feedforward

D. Feedbackward

C. Feedforward

2-5 pdf of required reading for pituitary function

Pituitary gland and hypothalamus are tightly related. T/F?

True

Thyroid-stimulating hormone

Dopamine inhibits the release of

Prolactin

Growth hormone stimulate the release of

Growth hormone

Somatostatin inhibits the release of

growth hormone

Vasopressin releases antidiuretic hormone

Thyroid affects metabolic rate and os needed for normal growth and development

**** review 13 mins in video for hormone and releases

Exocrine glands release

secretory products into the ducts for delivery to body surfaces

Pancreas has both endocrine and exocrine functions :

• Endocrine - releases hormones )insulin &

glucagon to regulate blood sugar)

• Exocrine - produce digestive enzymes to

breakdown fat, proteins, and carbohydrates

Slides 22 and 23

The _____ gland controls the _____ gland which forms a bridge between the nervous system and the endocrine system.

A. pituitary, hypothalamus

B. hypothalamus, pituitary

C. thalamus, pituitary

D. pituitary, thalamus

B. hypothalamus, pituitary

Clinical endocrine pathology includes

• Excess hormone

• Deficiency of hormone

• Visual impairment

Endocrine disorder classification: primary disorder

excess or deficiency of secretion by the target gland (Addison disease)

Endocrine disorder classification: secondary disorder

excess or deficiency of secretion by the pituitary gland (Cushing disease)

Endocrine disorder classification: tertiary disorder

excess or deficiency of secretion by the hypothalamus (hypothalamic trauma)

hyperptiuitarism

Overproduction of pituitary gland hormones, usually from

anterior pituitary gland

hyperpituitarism is most commonly caused by pituitary adenomas:

• Occur during 4th to 6th decade of life

• Usually benign

• Most common cause of hyperpituitarism

• Hormone production

Prolactinoma

-Occurs earlier in females (20-40 years old) compared to

males

• Females: galactorrhea, infertility, amenorrhea

• Males: decreased libido and impotence

GH-secreting adenomas

-Children will have gigantism if the adenoma occurs before

the closure of the epiphyseal plates

-Adults will have acromegaly if the adenoma occurs AFTER to closure if the epiphyseal plates

Gigantism

a condition produced by hypersecretion of growth hormone during the early years of life

Acromegaly

enlargement of the extremities characterized by growth in skin, soft tissue, thyroid gland, heart, liver, & bones (face hands, feet)

• Classic feature is acral enlargement - widening of the hands and feet, and coarsening of facial features

Acromegaly is caused by

Persistent elevated GH levels simulates insulin-like growth factor-1 (IGF-1) causing abnormal glucose tolerance & diabetes mellitus

Acromegaly s/s

May have muscle weakness, hypertension, arthritis,

osteoporosis, and congestive heart failure (CHF)

• Common orthopedic condition: carpal tunnel disease, low back pain, thoracic back pain

ACTH-secreting adenoma

-Stimulates the adrenal glands to produce too

much cortisol

Individuals with increased cortisol are more likely to develop

Cushing Disease

• Swollen puffy face, easy bruising, hyperglycemia,

hypertension, weight gain, excessive fat deposits in

face, and back of neck

Null cell adenoma

–No specific pituitary cell differentiation

–May be larger which causes mass effect (disturb other organs)

–Patient may demonstrate:

• Headache, visual abnormalities, and hypopituitarism

• May also have compression of CN III, IV, & VI resulting

in abnormal eye movements

hyperpituitarism treatment

-Surgery

-Drug therapy

-Chemotherapy

-Radiation

Hypopituitarism

•Decreased or absent hormonal secretion by the anterior

pituitary gland

•More than 75% of the gland must be affected to produce clinical symptoms

Causes of hypoituitarisim

– Tumors: Null cell pituitary adenoma as it grows and destroys tissue

– Removal of the pituitary gland

– Ischemic injury (ex. Obstetrical hemorrhage causes hypotension – decreased blood flow to anterior pituitary gland –pituitary necrosis)

– Reversible disorders: starvation, anorexia nervosa, severe anemia, GI tract disorders

Clinical presentation of hypopituitarism

1) GH deficiency

•Children: Short stature, delayed growth, delayed puberty

•Adults: Abdominal obesity, reduced strength and exercise

capacity

2) Adrenocortical insufficiency (ACTH deficiency)

•Hypoglycemia

•Anorexia

•Nausea

•Abdominal pain

•Orthostatic hypotension

3) Neurologic signs from tumors

•Headache

•Bilateral temporal hemianopia

•Loss of visual acuity

•Blindness

Hypopituitarism treatment

-Removal of tumor if possible

-Hormone replacement therapy

Posterior disorder: Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Increased retention of water by increased ADH leads to

hyponatremia

SIADH s/s

• Headache

• Anorexia

• Vomiting

• Confusion

• Stupor

• Coma and seizures

• Delirium and dementia

- Monitor for sudden weight gain/fluid retention

Posterior disorder: Diabetes insipidus

Hypofunction of the posterior pituitary gland resulting in

decreased levels of ADH

- decreased reabsorption of water by the kidneys

In a pt with diabetes insipidus, watch of side effects from ADH administration

• Increase BP

• Diarrhea

• Angina or MI

• Water intoxication

Thyrotixicosis

due to excessive secretion of thyroid hormone

• Increased metabolism throughout the body

What is the most common cause of hyperthyroidism?

Graves diseases

Graves' disease

-Increases T4 production

-Affects women more than men, (20-40 yrs)

-Goiter

Hyperthyroidism s/s

–Heat intolerance, sweating, and warm, flushed skin

–Weight loss associated with increased appetite

–Palpitations, tachycardia, tremor, anxiety, hyperactivity (Tachycardia, tremor, and sweating are due to increased sensitivity to catecholamines)

–Diarrhea

–Fine hair

–Exophthalmos

- Thyroid eye disease (TED) – progressive inflammation and damage to tissues around the eyes

exophthalmos

abnormal protrusion of the eyeball

Hyperthyroidism diagnosis

Clinical history, presentation, and lab tests

Hyperthyroidism intervention

-Antithyroid drugs - usual choice during pregnancy and if

under 12 years old

-Radioactive iodine for those 18 or older

-Surgery for very large glands

-Monitoring vital signs, consider heat intolerance and avoid

hot aquatic or pool PT setting

-Exercise intolerance and reduced exercise capacity

-May need hormone replacement if the thyroid is ablated

Thyroid storm is due to

inadequately treated hyperthyroidism

- potentially fatal

Tyrone storm s/s

-High fever

-Severe tachycardia

-Delirium

-Dehydration

-Extreme irritability or agitation

- STRESS!!

What are stressor for thyroid storm?

surgery, infection, toxemia of pregnancy, labor

and delivery, diabetic ketoacidosis. MI, PE, medication overdose

Hypothyroidism

• Deficiency of thyroid hormone

• Generalized slowed body metabolism

• Most common thyroid disease in the US

Hypothyroidism types

-Type 1/Primary hypothyroidism: hormone deficient

-Type 2/Secondary hypothyroidism: hormone resistant

Hypothyroidism is mostly caused by

autoimmune thyroiditis (Hashimoto's disease) or thyroid ablation (surgery, radiation, antithyroid

drugs)

Hypothyroidism diagnosis

Clinical history and lab tests

•Lab test for TSH, T3, T4

Hypothyroidism s/s

•Weight gain

•Cold intolerance and cool skin

•Thinning hair and loss of lateral portion of eyebrows

•Elevated diastolic blood pressure

•Bradycardia

•Congestive heart failure

•Carpal tunnel syndrome

•Apathy

•Facial edema

•Depression

•Menorrhagia

•Constipation

Hypothyroidism intervention

•Correct hormone deficiency & reverse symptoms

•Prevent further cardiac and arterial damage

•Consider neuromuscular symptoms, proximal muscle

weakness/pain, chronic fatigue

•Long term treatment with high doses of levothyroxine can

lead to bone fractures

*what are significant differences between hyper vs hypothyroidism

Hyper: exophthalmos (bug eyes), enlarged thyroid, tachycardia (heart failure), diarrhea, sweaty, hyper reflexes, weight loss

Hypo: puffy face, bradycardia (heart failure), constipation, cold intolerance, muscle weakness, edema in extremities, weight gain

Which of the following is a sign of

hyperthyroidism?

A. Weight loss

B. Constipation

C. Heat intolerance

D. Hair loss

A and C

Thyroid carcinoma

- most common endocrine cancer

- from past history of radiation to head or neck

- women > men

- painless nodule

- pts report problems with voice, swallowing, breathing

- treatable with surgery

- PT: stretching to prevent loss of motion to head, neck, and jaw especially neck dissection for Mets

hyperparathyroidism

-Overactivity of one or more of the parathyroid glands

-Affects more women that men over 60 years old

(postmenopausal)

-Can be primary, secondary, or tertiary

primary hypeparathyroidism

disruption of normal regulatory mechanism between

serum calcium levels and PTH secretion

Secondary hyperparathyroidism

glands are hypoplastic from malfunction of another

organ system such as renal failure

Tertiary hyperparathyroisim

mostly in patients receiving dialysis who have

longstanding hyperparathyroidism

Hyperparathyroidism disrupts:

calcium, phosphate, and bone metabolism

•Increased blood calcium causes bone damage, kidney damage, myalgias, and arthralgias

•Skeletal, articular and neuromuscular manifestations (Chronic low back pain, fracture, muscle weakness and atrophy, arthritis)

Hypoparathyroidism

-Hyposecretion, hypofunction, or insufficient secretion of

PTH

-Results in hypocalcemia, high serum phosphates, and

neuro and neuromuscular irritability (muscle tetany)

-May be idiopathic in origin or can occur with

thyroidectomy or other neck surgery

-May be autoimmune

-Can be life threatening

-Diagnosis: based on clinical presentation and labs - increased neuromuscular irritability (tingling)

Hypoparathyroidism treatment

•Oral Ca+

•IV calcium for severe cases

•Surgery is not recommended

Addison disease cause

- Primary adrenal insufficiency (idiopathic) or autoimmune

- Secondary adrenal insufficiency: Can be caused by long term use of corticosteriods and

infection

Addison disease s/s

-Hypoglycemia

-Hypotension

-Dehydration

-Weak & exhausted

-Loss of Na+ but retention of K+ (arrhythmias)

-Decreased resistance to stress

Addison disease Dx, intervention and prognosis

• Dx: blood and urine hormone analyses

• Intervention - replacement of glucocorticoids and mineral

corticoids

• Prognosis if untreated is fatal

Cushing syndrome causes

- Hyperfunction of the adrenal gland: Pituitary adenomas

- Excessive exogenous corticosteroid administration

Clinical signs of Cushing's syndrome

- Na+ and water retention

- Accumulation of adipose tissue

- Weight gain

- Breakdown of connective tissue (muscle, skin)

- Osteoporosis

- Weakness

- Hyperglycemia

- Hyperpigmentation

- Impairment of immune system

- Mental changes

*Addison vs Cushing disease?

Which of the following diseases disrupts/increases

calcium, phosphate, and bone metabolism?

A. Cushing disease

B. Addison disease

C. Hyperparathyroidism

D. Hypoparathyroidism

Hyperparathyroidism

Diabetes mellitus

Chronic systemic disorder

- Hyperglycemia

- Disruption of metabolism of carbohydrates, fats, and

proteins

What are the 2 types of diabetes mellitus

– Type 1 (also called insulin dependent DM or juvenile onset

DM): deficiency of insulin production and secretion (Autoimmune)

– Type 2 (also called non-insulin dependent DM or adult-

onset DM): cellular resistance to insulin and inadequate

insulin secretion (Being diagnosed in younger people due to obesity)

– Gestational: glucose intolerance during pregnancy

Type 1 diabetes mellitus

-Autoimmune

-Destruction of beta cells in the pancreas with little or no

insulin produced

-Genetic and environmental factors

-Risk factor: Presence of T1D in a first degree relative

-Treatment: insulin, diet, exercise

Type 2 diabetes mellitus

-Cellular insulin resistance

-Initially may have normal insulin production

-Accounts for 90% of all diabetes

Type 2 diabetes mellitus risk factors

•Family history

•Obesity

•> 45 y/o

•Sedentary lifestyle

•Previous gestational diabetes

•Hypertension

•Low HDL levels

•Smoking (cigarettes)

Type 2 diabetes treatments

oral or injectables for BS management, diet, exercise

Gestational diabetes mellitus

-Usually resolves about 6 weeks after the

pregnancy ends

-May be at higher risk of developing Type 2 DM in

the future

-Treatment: insulin, diet, exercise

Fasting blood sugar tests ranges

Diabetes: > 126mg/dL

Normal: <99mg/dL

Diabetes clinical presentation of type 1 and type 2

• Polyuria (excessive urination)-Type 1 and 2

• Polydipsia (excessive thirst)-Type 1 and 2

• Fatigue, weakness, dizziness-Type 1 and 2

• Poor wound healing-Type 1 and 2

• Peripheral neuropathies-Type 1 and 2

Diabetes clinical presentation of type 1 only

• Polyphagia (excessive hunger)-Type 1

• Weight loss-Type 1

• Ketonuria-Type 1

Hypoglycemia s/s

• <70 mg/dl

• Rapid onset

• Nervousness, shakiness

• Perspiration

• Tachycardia

• Weakness

• Headache

• Blurred vision

• Confusion

• Convulsions

• Coma

• Clamminess

Hyperglycemia s/s

•Blood glucose if >240mg/dl

•High level of ketones in the urine

•Lethargic

•Confused

•Frequent urination

•Increased thirst

•Coma

*Hyperglycemia can lead to:

Diabetes ketoacidosis

diabetic ketoacidosis clinical signs

• Thirsty or a very dry mouth

• Frequent urination

• High blood glucose (blood sugar) levels

• High levels of ketones in the urine

• Constantly feeling tired

• Dry or flushed skin

• Nausea, vomiting, or abdominal pain, especially >2hrs

• Difficulty breathing (Kussmaul respirations)

• Fruity odor on breath

• Difficulty paying attention, or confusion

• Glucose> 300mg/dL,

• pH<7.3

• Bicarbonate level <18 mEq/L

What are general complication of diabetes mellitus (DM)?

- diabetic neuropathy

- atherosclerosis

- diabetic retinopathy

- stoke

- autonomic nerves- urinary incontinence and impotence

- peripheral neuropathy

Complication of DM: diabetic nephropathy

• Kidney damage/failure:

– Glomerulosclerosis (scarring of the filtering part of the kidneys)

– Pyelonephritis (kidney infection)

– Papillary necrosis (renal papillae, where urine flows into the ureters, die)

• Hypertension

Complication of DM: cardiovascular system - Atherosclerosis

-Coronary heart disease

-Cerebrovascular diseases

-Aortic aneurysm

-Narrowing and occlusion of lower-extremity arteries can

cause tissue necrosis