endocrine physiology and disorders
DESCRIPTION
Endocrine Physiology and 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. - PowerPoint PPT PresentationTRANSCRIPT
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Endocrine Physiologyand
Disorders
Endocrine Physiologyand
Disorders
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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
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Solubility of Hormones Determines Mechanism of Action
Lipid soluble hormones steroid thyroid
Water soluble hormones proteins and peptides catecholamines
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anterior posterior
liverGH
ACTHadrenalcortex
TSH
thyroidPRL FSH, LH
ADH
Oxytocin
kidney
breastuterus
Feedback Regulation
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Feedback Regulation
anterior posterior
GH
ACTH
TSH
PRL FSH, LH
ADH
Oxytocin
somatomedin
cortisol
T3, T4
osmolality
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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
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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.
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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
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Causes of endocrine disorders
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Acromegaly
GH secreting pituitary adenoma headache, visual disturbances hyperglycemia “diabetogenic” increased lean body mass
– bone and soft tissue
Treatment hypophysectomy irradiation
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Thyroid Hormone Synthesis
thyroglobulin
T3 T4
YTSH
T3, T4 secretionThyroid Hormonesynthesis is doneby the enzyme:Thyroid Peroxidase
Iodine
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Triiodothyronine and Thyroxine
About 90% is T4
Most abundant
About 10% is T3
Most biologically active
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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
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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
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Etiology of Hyperthyroidism
Primary
Graves Disease
Thyroid tumor
Thyroiditis
Secondary
Pituitary adenoma
Exogenous thyroid
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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
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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
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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
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Hypothyroidism
History
weight gain
fatigue
amenorrhea
cold intolerance
constipation
Physical
dry, dull skin
coarse hair
hoarse voice
low HR, BP
decreased DTR
periorbital edema
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Hypothyroidism
Primary
Hashimoto thyroiditis
Iatrogenic (surgery, RAIU ablation)
Iodine deficiency
Secondary
Pituitary failure
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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
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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.
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Adrenocortical Hormones
Sugar: glucocorticoids (cortisol)
Salt: mineralocorticoids (aldosterone)
Sex: androgens, estrogens
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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
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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
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Adrenocortical Hypersecretion
History
weight gain
fatigue
menstrual irregularity
weakness
easy bruising
Physical
central obesity
muscle wasting
striae
hyperglycemia
hypertension
hirsutism
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Etiology
Cushing Disease
Pituitary adenoma
Cushing Syndrome
Adrenal adenoma
Adrenal carcinoma
Ectopic ACTH (cancer)
Exogenous steroids
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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)
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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
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Adrenocortical Insufficiency
History
may be asymptomatic
weakness
weight loss
Physical
hyperpigmentation
tachycardia
hypotension
hypoglycemia
hyperkalemia
ACUTE: N&V, headache, bleeding
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Etiology
Primary
autoimmune
adrenalectomy
infarction
congenital aplasia
congenital enzyme deficiency (Adrenogenital syndrome)
Secondary
pituitary failure
steroid withdrawal
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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)
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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
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Regulation of Insulin Secretion
glucagon
somatostatin insulin
GLUCOSEGlut-2
Increased secretionof Insulin
Decreasesblood glucose
Liver
Releasesglucoseandketones Endocrine Pancreas
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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
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Figure: 41-4Metabolism in type 1 diabetes
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What hormones affect blood glucose level?
Hormones that increase glucose: growth hormone catecholamines glucagon thyroid glucocorticoids
Hormones that decrease glucose: insulin
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Somogyi Phenomenon
Hypoglycemia Release of:growth hormonecatecholaminesglucagoncortisol
Insulinadministration Hyperglycemia
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Diabetes MellitusDiabetes Mellitus
Insulin Dependent (Type 1)
Non Insulin Dependent (Type 2)
Insulin Dependent (Type 1)
Non Insulin Dependent (Type 2)
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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
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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%
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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
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Compare DKA with HHNS
DKA
ketoacidosis
mod elevated glucose
HHNS
no ketoacidosis
high glucose >800
severe dehydration
coma
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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
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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
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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
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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)
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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
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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
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The End…