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
Solubility of Hormones Determines Mechanism of Action
•	Lipid soluble hormones
•	steroid
•	thyroid
•	Water soluble hormones
•	proteins and peptides
•	catecholamines
 Feedback Regulation

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

Acromegaly
•	GH secreting pituitary adenoma
•	headache, visual disturbances
•	hyperglycemia “diabetogenic”
•	increased lean body mass
–	bone and soft tissue
•	Treatment
•	hypophysectomy
•	irradiation
Thyroid Hormone Synthesis
Triiodothyronine and Thyroxine
•	About 90% is T4
	Most abundant

•	About 10% is T3
	Most biologically active
Actions of Thyroid Hormones
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:  b-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
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
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?
•	Hormones that increase glucose:
•	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	obese
Immune-mediated	YES	NO
Ketoacidosis 	YES 	NO
Insulin secretion 	NO 	YES
Beta cell function 	NO 	YES
HLA-linkage 	YES 	NO
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
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
KNOW THE DIFFERENCE