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Endocrine Physiology
and
Disorders
Endocrine Systems
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Intercellular communication network
Hormones travel from cell to cell through the bloodstream
Regulates complex phenomenon:
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Stress Response
Growth and Development
Fluid and Electrolyte Balance
Reproduction
Solubility of Hormones Determines Mechanism of Action
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Lipid soluble hormones
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steroid
thyroid
Water soluble hormones
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proteins and peptides
catecholamines
Feedback Regulation
Negative Feedback
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Feedback signals decrease secretion by
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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
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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
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Hyperfunction
Etiology
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Treatment
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surgical removal
blocking drugs
irradiation
Hypofunction
Etiology
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autoimmune stimulation
secreting tumors
idiopathic
autoimmune inhibition
nonsecreting tumors
surgical removal
ischemia, infarct
receptor defects
Treatment
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hormone therapy
Acromegaly
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GH secreting pituitary adenoma
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headache, visual disturbances
hyperglycemia “diabetogenic”
increased lean body mass
– bone and soft tissue
Treatment
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hypophysectomy
irradiation
Thyroid Hormone Synthesis
Triiodothyronine and Thyroxine
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About 90% is T4
Most abundant
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About 10% is T3
Most biologically active
Actions of Thyroid Hormones
Hyperthyroidism
History
 weight loss
 increased appetite
 nervousness
 heat intolerance
 palpitations
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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
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Etiology: Autoimmune
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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
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RAIU ablation
Symptom control with beta blockers
PTU and thyroxine to inhibit synthesis
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thyroxine may reduce relapse which often occurs with PTU alone
Surgery
Thyroiditis
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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
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Hypothyroidism
Primary
 Hashimoto thyroiditis
 Iatrogenic (surgery, RAIU ablation)
 Iodine deficiency
Secondary
 Pituitary failure
Laboratory Evaluation
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T3, T4 may initially be normal or low
TSH is a better indicator of hypothyroid
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Primary hypothyroid: high TSH
Secondary hypothyroid: low TSH
Replacement of thyroid hormone
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Synthetic T4 (Synthroid)
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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
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Sugar: glucocorticoids (cortisol)
Salt: mineralocorticoids (aldosterone)
Sex: androgens, estrogens
Regulation of Cortisol Secretion
Actions of Cortisol
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Metabolism: gluconeogenesis, insulin antagonist, increased appetite, mobilization of
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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
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24-hr urinary free cortisol (increased)
Dexamethasone suppression test:
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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
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If on exogenous steroids, try to wean
If tumor, surgery or irradiation
If inoperable, drugs to inhibit synthesis
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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
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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
Major Actions of Insulin
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+
Figure: 41-4
Metabolism in type 1 diabetes
What hormones affect blood glucose level?
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Hormones that increase glucose:
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growth hormone
catecholamines
glucagon
thyroid
glucocorticoids
Somogyi Phenomenon
Diabetes Mellitus
Insulin Dependent (Type 1)
Non Insulin Dependent (Type 2)
Compare Type 1 and Type 2
Onset any age
adults
Weight
underweight
Immune-mediated YES
Ketoacidosis
YES
Insulin secretion
NO
Beta cell function NO
HLA-linkage YES NO
obese
NO
NO
YES
YES
Diagnostic Criteria
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Nonpregnant Adults:
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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:
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fasting glucose < 126 mg%, 2 hr OGTT is between 126-200, 0-2 hr is > 200
mg%
Pathogenesis of Diabetes
Compare DKA with HHNS
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DKA
ketoacidosis
mod elevated glucose
HHNS
no ketoacidosis
high glucose >800
severe dehydration
coma
Goals of Treatment
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Normalize Blood Glucose
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<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
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Avoid Long-term Vascular and Neurological Complications
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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
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Diet:
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low in simple sugars, fat. Adequate protein and complex carbohydrates
weight loss for obese Type 2
Exercise
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consistent, regular timing
Drug therapy
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Insulin for both Type 1 and Type 2
oral agents for Type 2 only
ACE Inhibitors
Oral Agents for Diabetes
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Sulfonylureas (hypoglycemics, increase secretion of insulin from
pancreas)
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First generation: Tolinase, Diabinese
Second generation: Diabeta, Glucotrol
Biguanides (decrease tissue resistance, do not cause hypoglycemia)
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metformin (Glucophage)
Teaching, Teaching, Teaching
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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
KNOW THE DIFFERENCE