Endocrine Physiologyand

Disorders

Endocrine Physiologyand

Disorders

Endocrine Systems

Intercellular communication network

Hormones travel from cell to cell through the bloodstream

Regulates complex phenomenon: Stress Response Growth and Development Fluid and Electrolyte Balance Reproduction

Solubility of Hormones Determines Mechanism of Action

Lipid soluble hormones steroid thyroid

Water soluble hormones proteins and peptides catecholamines

anterior posterior

liverGH

ACTHadrenalcortex

TSH

thyroidPRL FSH, LH

ADH

Oxytocin

kidney

breastuterus

Feedback Regulation

Feedback Regulation

anterior posterior

GH

ACTH

TSH

PRL FSH, LH

ADH

Oxytocin

somatomedin

cortisol

T3, T4

osmolality

Negative Feedback

Feedback signals decrease secretion by down regulation of receptor number decreased sensitivity of receptors

– eg. thyroid hormone down regulates TRH receptors on thyrotroph cells in the pituitary

Primary vs Secondary Disorders

Primary Disorders are due to dysfunction of the target gland.

Secondary Disorders are due to dysfunction of the pituitary gland.

Primary and secondary can be differentiated by looking at feedback loops.

Endocrine Disorders

Hyperfunction

Etiology autoimmune

stimulation secreting tumors idiopathic

Treatment surgical removal blocking drugs irradiation

Hypofunction

Etiology autoimmune inhibition nonsecreting tumors surgical removal ischemia, infarct receptor defects

Treatment hormone therapy

Causes of endocrine disorders

Acromegaly

GH secreting pituitary adenoma headache, visual disturbances hyperglycemia “diabetogenic” increased lean body mass

– bone and soft tissue

Treatment hypophysectomy irradiation

Thyroid Hormone Synthesis

thyroglobulin

T3 T4

YTSH

T3, T4 secretionThyroid Hormonesynthesis is doneby the enzyme:Thyroid Peroxidase

Iodine

Triiodothyronine and Thyroxine

About 90% is T4

Most abundant

About 10% is T3

Most biologically active

Actions of Thyroid Hormones

T3

T4 T3

T3 combines with a nuclearreceptor--------> affects DNA: increased oxygen use increased BMR increased heat production increased cardiac output increased ventilation gluconeogenesis enhanced SNS actions

plasmamembrane

rT3

Hyperthyroidism

History

weight loss

increased appetite

nervousness

heat intolerance

palpitations

increase bowel motility

Physical

warm, moist skin

thin, fine hair

increased BP, HR

hyperreflexia

fine tremor

eyelid, retraction, lag

enlarged thyroid

Etiology of Hyperthyroidism

Primary

Graves Disease

Thyroid tumor

Thyroiditis

Secondary

Pituitary adenoma

Exogenous thyroid

Pathophysiology of Graves Dx

Etiology: Autoimmune High association with HLA D3 and B8 Women affected 8 to 1

Pathogenesis: IgG autoantibodies bind to and stimulate TSH receptors on thyroid. Thyroid hyperplasia and hypersecretion result

Exophthalmos due to IgG

Treatment

RAIU ablation

Symptom control with beta blockers

PTU and thyroxine to inhibit synthesis thyroxine may reduce relapse which often

occurs with PTU alone

Surgery

Thyroiditis

Initially: Increased thyroid hormone release leads to hyperthyroidism, but RAIU is low and synthesis is low

Next: Hormone depletion leads to a period of hypothyroidism

Finally: Most will recover and become euthyroid in 2-6 months

RX: -blockers, NSAID, ASA, steroids

Hypothyroidism

History

weight gain

fatigue

amenorrhea

cold intolerance

constipation

Physical

dry, dull skin

coarse hair

hoarse voice

low HR, BP

decreased DTR

periorbital edema

Hypothyroidism

Primary

Hashimoto thyroiditis

Iatrogenic (surgery, RAIU ablation)

Iodine deficiency

Secondary

Pituitary failure

Laboratory Evaluation

T3, T4 may initially be normal or low

TSH is a better indicator of hypothyroid Primary hypothyroid: high TSH Secondary hypothyroid: low TSH

Replacement of thyroid hormone

Synthetic T4 (Synthroid) average dose is 110 - 120 mcg/day

Monitor TSH level

Overtreatment can lead to osteoporosis in postmenopausal women: If TSH too low, reduce replacement dose.

Adrenocortical Hormones

Sugar: glucocorticoids (cortisol)

Salt: mineralocorticoids (aldosterone)

Sex: androgens, estrogens

Regulation of Cortisol Secretion

7-13 Pulses per day of CRH fromhypothalamus

Sleep-wake patternlight-dark cycle

Stresspaininfectioncortisol level

ACTH secretion

Cortisol peak at 2:00-4:00 amCortisol nadir at 10 pm -midnight

Actions of Cortisol

Metabolism: gluconeogenesis, insulin antagonist, increased appetite, mobilization of fat stores

Muscle: increased contractility, breakdown of protein to form glucose

Bone and Connective: decreased bone and collagen formation

Vascular: enhances effect of catecholamines, reduces vascular permeability, mineralocorticoid effects

Immune: inhibits the immune system in a number of ways

CNS: alters auditory, olfactory and taste acuity, mood, sleep

Adrenocortical Hypersecretion

History

weight gain

fatigue

menstrual irregularity

weakness

easy bruising

Physical

central obesity

muscle wasting

striae

hyperglycemia

hypertension

hirsutism

Etiology

Cushing Disease

Pituitary adenoma

Cushing Syndrome

Adrenal adenoma

Adrenal carcinoma

Ectopic ACTH (cancer)

Exogenous steroids

Laboratory Evaluation

24-hr urinary free cortisol (increased)

Dexamethasone suppression test: If suppression of cortisol, then secondary

Plasma ACTH (low in primary, high in secondary)

CRH stimulation test (increases cortisol in secondary, no effect in primary)

Treatment of Cushing Syndrome

If on exogenous steroids, try to wean

If tumor, surgery or irradiation

If inoperable, drugs to inhibit synthesis e.g. Mitotane, and inhibitors of enzymes in

the cortisol pathway

Adrenocortical Insufficiency

History

may be asymptomatic

weakness

weight loss

Physical

hyperpigmentation

tachycardia

hypotension

hypoglycemia

hyperkalemia

ACUTE: N&V, headache, bleeding

Etiology

Primary

autoimmune

adrenalectomy

infarction

congenital aplasia

congenital enzyme deficiency (Adrenogenital syndrome)

Secondary

pituitary failure

steroid withdrawal

Laboratory Evaluation

Plasma cortisol level (low)

ACTH level (high in primary, low in secondary)

ACTH stimulation test (no response in primary)

Serum potassium (high if associated deficiency of aldosterone)

Serum glucose (low)

Replacement Therapy

ACUTE

Hydrocortisone 100mg now, then continuous infusion for 24 hr.

Fluid replacement

Convert to oral meds if stable

CHRONIC

Prednisone, cortisone and hydrocortisone are used

Twice daily dosing, 2/3 in am, 1/3 in pm

Regulation of Insulin Secretion

glucagon

somatostatin insulin

GLUCOSEGlut-2

Increased secretionof Insulin

Decreasesblood glucose

Liver

Releasesglucoseandketones Endocrine Pancreas

Action on Cell Effect on Blood

glucose uptake blood glucose

glycogen formation

gluconeogenesis

protein synthesis blood amino acids

fat deposition blood FFA

lipolysis blood ketones

K+ uptake blood K+

Major Actions of Insulin

Figure: 41-4Metabolism in type 1 diabetes

What hormones affect blood glucose level?

Hormones that increase glucose: growth hormone catecholamines glucagon thyroid glucocorticoids

Hormones that decrease glucose: insulin

Somogyi Phenomenon

Hypoglycemia Release of:growth hormonecatecholaminesglucagoncortisol

Insulinadministration Hyperglycemia

Diabetes MellitusDiabetes Mellitus

Insulin Dependent (Type 1)

Non Insulin Dependent (Type 2)

Insulin Dependent (Type 1)

Non Insulin Dependent (Type 2)

Onset any age adults

Weight underweight obese

Immune-mediated YES NO

Ketoacidosis YES NO

Insulin secretion NO YES

Beta cell function NO YES

HLA-linkage YES NO

Type 1

Compare Type 1 and Type 2

Type 2

Diagnostic Criteria

Nonpregnant Adults: random glucose > 200 mg% plus symptoms OR: fasting glucose > 126 mg%, twice OR: fasting glucose < 126 mg%, but OGTT

is > 200 mg% at 2 hours

Impaired Glucose Tolerance: fasting glucose < 126 mg%, 2 hr OGTT is

between 126-200, 0-2 hr is > 200 mg%

Pathogenesis of Diabetes

Impaired Transport of Glucoseinto Cells

HYPERGLYCEMIA CELL ENERGY

breakdown offat and protein

ketogenesis

blood osmolality

cells shrink glycosuria

dehydration

thirst HR warm,dryFruity Kussmaul Comabreath resp

Compare DKA with HHNS

DKA

ketoacidosis

mod elevated glucose

HHNS

no ketoacidosis

high glucose >800

severe dehydration

coma

Goals of Treatment

Normalize Blood Glucose <180 mg% postprandial, <130 mg% fasting

– Self monitor blood glucose routinely

– Normal blood glucose: 70-115 mg%

– Minimize hypoglycemic events Keep HbA1c < 7.0% (3.9-6.9%)

– Reflects glucose level over past 2-3 months

– HbA1c increases 1% for each increase of 30mg% in blood glucose

Goals of Treatment

Avoid Long-term Vascular and Neurological Complications Glycosylated proteins, enzymes contribute to

atherosclerotic processes:

– retinopathy, nephropathy, MI, CVA, peripheral vascular disease

Neurons don’t require insulin, are exposed to high intracellular glucose:

– peripheral neuropathy, autonomic neuropathy

Treatment of Diabetes

Diet: low in simple sugars, fat. Adequate protein and complex

carbohydrates weight loss for obese Type 2

Exercise consistent, regular timing

Drug therapy Insulin for both Type 1 and Type 2 oral agents for Type 2 only ACE Inhibitors

Oral Agents for Diabetes

Sulfonylureas (hypoglycemics, increase secretion of insulin from pancreas) First generation: Tolinase, Diabinese Second generation: Diabeta, Glucotrol

Biguanides (decrease tissue resistance, do not cause hypoglycemia) metformin (Glucophage)

Teaching, Teaching, Teaching

Blood glucose monitoring

Urine ketone monitoring

Drug onset, peak

Short and long term complications to monitor

When to call the provider, enter the hospital

Diet and Exercise plan

HIGHBlood Sugar

HIGHBlood Sugar

LOW Blood Sugar

LOW Blood Sugar

Increased thirst and urination

ketones in urine

aching, weak

heavy breathing

nausea,vomiting

fatigue

Increased thirst and urination

ketones in urine

aching, weak

heavy breathing

nausea,vomiting

fatigue

cold sweats

headache

trembling

pounding heart

sleepiness

personality change

hunger

cold sweats

headache

trembling

pounding heart

sleepiness

personality change

hunger

KNOW THE DIFFERENCE

The End…