Patho Wk 7: Endocrine

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ENDOCRINE PATHOPHYSIOLOGY PART 2

ENDOCRINE DISORDERS:

Primary Disorder = Defect within the gland

o Ex: Primary hypothyroidism

Secondary Disorder = Over/under stimulation

o Ex: Pituitary Secondary hyperaldosteronism or hypothyroidism

Hypersecretion = Hormone excess

ETIOLOGY:
o Over-stimulation
o Secreting tumors
o Ectopic hormone production
o Exogenous hormones (corticosteroids)
o Antibodies
o Gland destruction

TREATMENT:
o Surgery
o Chemical ablation
o Stop hormone replacement
Hyposecretion = Too little hormone

ETIOLOGY:
o Under-stimulation
o Autoimmunity
o Non-secreting tumor
o Ischemia
o Infarction
o Surgical removal (tx for hyperthyroid remove thyroid leads to hypothyroidism)
o Receptor defects

TREATMENT:
o Hormone replacement therapy
SIADH = Syndrome of Inappropriate ADH secretion

Hypersecretion of ADH causing excessive reabsorption of water by the kidney

CAUSES:
o Tumors
o Head trauma
o IV fluids
o PNA, Infxns, drugs

SIGNS/SYMPTOMS:
o Hyponatremia
o Hemodilution
o CNS changes (r/t how low Na+ level is)

TREATMENT = RAISE NA+ LEVEL

o Water restriction
o Administer sodium (hypertonic saline, 3%)
o Furosemide to block circulatory overload (pee out water)
o Chronic SIADH Give drugs to block the renal response to ADH

demeclocycline hydrochloride (tertracycline abx)

lithium
o Surgical removal of ADH-secreting tumors

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DIABETES INSIPIDUS

Hyposecretion of ADH or insensitivity to ADH

o Central (neurogenic) deficiency of ADH from posterior pituitary
o Nephrogenic renal insensitivity to ADH

Distal and collecting ducts of the nephrons fail to reabsorb water

o Psychogenic drinking too much water

CAUSES:
o Central brain injury, stroke, *pituitary tumors, infection
o Nephrogenic renal disease, medications (lithium, methicillin)
o Psychogenic polydipsia

SIGNS/SYMPTOMS:
o Hypernatremia
o Polyuria
o Dehydration
o Thirst
o Findings indicative of cause

TREATMENT:
o IM or intranasal administration of ADH
o Oral hypoglycemic agents (increase the response of the renal tubule to ADH)
o Thiazide diuretics (induce a state of salt depletion)

GROWTH HORMONE
1) GIGANTISM (Child) / ACROMEGALY (Adult) Hypersecretion of growth hormone

CAUSE:
o *Benign pituitary tumor

2)

SIGNS/SYMPTOMS: (pic)
o Increased ring, hat, shoe, and glove size
o Impotence in men
o Amenorrhea in women
o Deepening of the voice
o Thick, fleshy face
o Enlarged lips, nose, and ears
o Proganthism
o Enlarged internal organs
o Osteoporosis and arthritis develop

TREATMENT = SURGERY
o Transphenoidal hypophysectomy (remove pituitary)

Sequelae:

Transient devel of diabetes insipidus

Lifelong hormone replacement

o Radiation possibly considered
o Medications that block effects of growth hormone

DWARFISM Hyposecretion of growth hormone

CAUSE:
o Pituitary not producing adequate amounts

SIGNS/SYMPTOMS:
o Small stature

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Patho Wk 7: Endocrine

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Slow growth rate

Late onset or absence of puberty
Normal intelligence!

TREATMENT:
o Daily growth hormone injections, but not very successful
CUSHINGS SYNDROME Manifestation of hypercortisolism (PICS)

CAUSE:
o Hypersecretion of ACTH excess cortisol
o Adrenal tumors
o Exogenous Chronic steroid use

SIGNS/SYMPTOMS:
o Hyperglycemia
o Hypernatremia
o Hypokalemia
o Thin skin (striae)/truncal obesity
o *Moon face/buffalo hump
o *Elevated am cortisol

TREATMENT:
o DEC or d/c steroids
o Surgery if endogenous, ectopic
o Manage electrolyte imbalance

ADDISONS DISEASE Insufficient production of adrenocortical hormones

CAUSE:
o Autoimmune
o Cancer
o Pituitary failure

SIGNS/SYMPTOMS:
o Hypoglycemia
o Hyponatremia
o Hyperkalemia
o *Low am plasma cortisol
o Skin Hyperpigmentation (PIC)
TREATMENT:
o Endocrine referral
o Glucocorticoid and mineralocorticoid replacement (life-long!)

Hydrocortisone

Florinef
May progress to ADDISONIAN CRISIS
o Usually related to infection
o Metabolic acidosis
o Hemodynamic instability
o Death
o Want to avoid stress!

Must be treated with stress-dose hydrocortisone to prevent shock rxn

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Patho Wk 7: Endocrine

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HYPERALDOSTERONISM Excessive secretion of aldosterone (in renin-angiotensin-aldo loop)

- Primary disorder = Conns Disease

- Secondary disorder

CAUSE:
o Adrenocortical neoplasm
o Sustained renin release (secondary)

SIGNS/SYMPTOMS:
o HTN difficult to control!
o Hypokalemia

Muscle weakness, weakness, paralysis, cardiac dysrhythmia

o Hypernatremia

TREATMENT:
o ACE inhibitor and/or surgery to remove gland
PHEOCHROMOCYTOMA Catecholamine-secreting tumor of the adrenal medulla resulting in excess catechols (epi/norpei)

SIGNS/SYMPTOMS:
o *Hypertension (labile)
o Tachycardia
o Palpitations, diaphoresis, and flushing
o N&V, blurred vision, and headaches
o Hyperventilation
o Hyperglycemia
o Appear nervous

TREATMENT:
o Surgery main tx
o Regitine
HYPOTHYROIDISM Absent or d level of circulating thyroid hormone

Cretinism (child)

Myxedema (adult)

CAUSES:
o Congenital
o Insufficient iodine in the diet
o Surgery: Partial or complete thyroidectomy
o Irradiation
o Amiodarone (Cardiac)

SIGNS/SYMPTOMS EVERYTHING SLOWS DOWN!

o No energy!
o d basal metabolic rate weight gain, fatigue
o Cold intolerance
o Edema/puffiness
o Mental retardation (child)
o Dry skin
o Myxedema coma profound hypothyroid state

LOC/confusion progressing to coma if not reversed

LABS: Elevated TSH, low-normal T4, low T3

TREATMENT:
o Thyroid hormone life-long!

HYPERTHYROIDISM : GRAVES DZ Excess production of thyroid hormone

CAUSES:
o More common in women (8:1)

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Familial
May be autoimmune (antibodies to thyroid hormone)
Amiodarone can cause both hypo or hyper r/t mechanism

SIGNS/SYMPTOMS EVERYTHING SPEEDS UP!

o Goiter (PIC)
o d basal metabolic rate weight loss
o d heart rate (atrial fibrillation!)
o d blood pressure
o d GI motility
o Heat intolerance
o Nervousness
o *Exophthalmos (late finding) non-reversible!
LABS: Low TSH, elevated T3 and T4
TREATMENT:
o Endocrine consult
o Symptom relief beta blocker (Propanolo/Inderal)
o *Surgery or Radioactive iodine Destroys goiter

HYPERTHYROIDISM: THYROTOXICOSIS Excess production (LOTS) of thyroid hormone

Inadequate control of hyperthyroidism (worst presentation)

Deadly hyper-metabolic state

CAUSE:
o Systemic infections
o Uncontrolled diabetes
o Stress: Trauma
o Myocardial infarction
o Thyroid ablation
o Thyroid medication overdose

PATHOPHYSIOLOGY:
o d basal metabolic activity (BMR)
o Stimulates beta adrenergic receptors
o d neural excitability (seizures)
o d heat production
o d cellular O2 consumption (inc metabolic demand)
o d energy production
o O2 demand exceeds O2 supply
o Tachycardia
o *Critically high fever
o Appetite s
o Carbohydrates, fats, and proteins, are mobilized to attempt to meet metabolic demands

PATHOPHYSIOLOGY: cont
o Nitrogen and uric acid excretion increases
o Metabolic acidosis
o Intestinal peristalsis increases
o Dehydration
o Malnutrition
o Tachy-arrhythmias, CHF, and pulmonary edema

THYROTOXICOSIS Goals of treatment = must turn off the mechanism! DEC production/release of thyroid hormone

Reduce production of thyroid hormone

o propylthiouracil (PTU)
o methimazole (Tapezole)

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Reduce the release of thyroid hormone

o Iodine drugs (Sodium iodide, SSKI)
o Dexamethasone (Decadron)
Reduce conversion of T4 to T3
o Use acetaminophen instead of aspirin
Suppress adrenergic and catecholamine receptors (treating the symptoms)
o Propranolol (Inderal)
Control pyrexia
o Cooling blanket
o Acetaminophen
o Dantrolene last measure
Increase O2 supply (demand exceeding supply)
o 100% oxygen
Treat dehydration
o Give large volumes of IVF with glucose
Control metabolic acidosis
o 100% O2
o NaHCO3
Treat congestive heart failure
o Digitalis (Digoxin) myocardial contractility
o Diuretics fluid removal

HYPERparaTHYROIDISM

Primary hyperparathyroidism
o Excess secretion of PTH from one or more parathyroid glands (4 glands total)
o 85% caused by parathyroid adenomas

Secondary hyperparathyroidism r/t other diseases

o Increase in PTH secondary to a chronic disease

Renal failure

Dietary deficiency of vitamin D, calcium

CLINICAL SIGNS: (urine)

o Hypercalciuria
o Alkaline urine
o Hyperphosphaturia Predisposes to the formation of calcium stones
HYPOparaTHYROIDISM

Usually caused by parathyroid damage in thyroid surgery

Abnormally low PTH levels

o d serum calcium level
o d serum phosphate level

CLINICAL SIGNS:
o Hypocalcemia

Lowering of the threshold for nerve and muscle excitation

Muscle spasms; hyperreflexia; tonic-clonic convulsions; laryngeal spasms; death from asphyxiation
o Phosphate retention
ENDOCRINE PATHOPHYSIOLOGY PART 3
DIABETES MELLITUS

Chronic disorder of metabolism characterized by a lack of insulin

o Relative lack or Absolute lack (Type I)
o Characterized by hyperglycemia
o Approximately 14 million people affected

CLASSIFICATIONS:

Patho Wk 7: Endocrine

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Type 1 (absolute)
Type 2
Secondary or other
Gestational

PREDISPOSING FACTORS:
o Genetics
o Diet high in saturated fats
o Obesity
o Pregnancy
o Autoimmunity
o Lack of insulin receptors on cells

INSULIN hormone secreted from islet of langerhan cells of pancreas

o Promotes glucose transport into cells
o s glucose utilization
o s glycogenesis & glycolysis
o s blood glucose
o Promotes fatty acid transport into cells
o Promotes lipogenesis (s fat storage)
o s fat mobilization

HYPOGLYCEMIA Serum glucose < 70 mg/dl

MANIFESTATIONS:
o Hunger, Weakness, Tremor
o Diaphoresis, Cold, Clammy
o Low plasma blood sugar
HYPERGLYCEMIA Serum glucose >105 (fasting) or >140 (postprandial)

Non-diabetic!

MANIFESTATIONS:
o Polydipsia
o Polyphagia
o Polyuria
o Dehydration
o Blurred vision
o Elevated plasma blood glucose
TYPE 1 DM absolute deficiency of insulin

CHARACTERISTICS:
o Onset in childhood and adolescence
o Catabolic state (breaking down)
o First development of ketosis (ketones present in urine)
o Autoimmune destruction of beta cells absolute deficiency of insulin!

Thought to be r/t genetic/environmental interaxn

o Requires life-long insulin therapy
o Presence of human leukocyte antigens

HLA-DR3 or HLA-DR4

PATHOPHYSIOLOGY:
o NO insulin production
o Beta cells non-functional

*LAB DIAGNOSIS: (Type 1 or Type 2!)

o Fasting glucose: >/= 126 on 2 separate occasions
o Random glucose: >/= 200 with polyuria, polydipsia, and weight loss
o Glucose tolerance test: Oral glucose ingested, test at intervals. If glucose >/= 200 at 2-hr interval
o HgbA1c: Normal 5.5 7%

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NOT used for diagnosis in Type 1

TREATMENT:
o Insulin Injections!!
o Endocrine consult
o Diabetes Educator referral

SOMOGYI EFFECT = Nocturnal hypoglycemia causing surge of counter-regulatory/compensatory hormone

o d am blood sugar but d 3am blood sugar (hypoglycemic)

Cortisol is released in response to the hypoglycemia, causing high am blood sugar

o TREAT: by lowering or deleting HS (bedtime) insulin dose

DAWN PHENOMENON = Decreased sensitivity to insulin at night

o d am blood sugar and d 3am blood sugar
o TREAT: by adding or increasing HS insulin dose

TREATMENT OF DM INSULIN!

Must be given parenterally

Used for both Type 1 (always) and Type 2

EXAMPLES:
o Regular insulin (short-acting)
o NPH insulin
o Intermediate acting insulin
o Long acting sustained release
o Mixed NPH/Regular
o Insulin pumps (infuses regular insulin)

DIABETIC KETOACIDOSIS (DKA) Acute complication of DM

Intracellular dehydration secondary to elevated blood glucose

SIGNS/SYMPTOMS:
o Hyperglycemia
o Polyuria/Polydipsia
o *Ketonuria/Ketonemia
o *Metabolic acidosis
o *HyperK+
o *Fruity breath
o Kussmauls respirations
o Changed LOC
o Orthostatic hypotension and tachycardia
o Elevated BUN/Cr

TREATMENT:
o Isotonic IVF (NS): 1 liter in 1 hour, then 500cc/hr

Change to NS or D5NS depending on glucose level

o Insulin/Glucose Stabilizer Protocols
o Bicarbonate gtt for severe acidosis
o May require intubation monitor WOB and oxygenation
o Do NOT treat initial hyperK+ will correct when you tx the glucose level and DKA (follow K levels)

TYPE 2 DM insulin resistance

Most common type of diabetes

Onset usually after the age of 40 (but getting much younger!)

Patho Wk 7: Endocrine

CHARACTERISTICS:
o Resistance to insulin action
o Defective glucose-mediated insulin secretion

May or may not require insulin therapy (b/c dont have absolute insulin deficiency)
o Absence of ketones
o Associated with Metabolic Syndrome

TREATMENT control blood sugar

o Oral Hypoglycemic Drugs

Stimulate beta cells to secrete insulin in pancreas

May increase cellular receptors for insulin

o Examples

Glyburide
Glucatrol

Tolinase
Diabenese

Diabeta
Glucophage

Januvia

METABOLIC SYNDROME type 2 DM precursor; however, it is NOT actually diabetes

CHARACTERISTICS:
O Central Obesity
o Insulin Resistance
o HTN
o d lipids
o d aldosterone
o d facial hair growth
o d skin pigmentation
o **d risk for CVD

TREATMENTS:
o Weight loss
o Blood sugar control
o Lipid management
o BP control
o Aldactone (K-sparing diuretic)
HYPEROSMOLAR HYPERGLYCEMIC NONKETOSIS (HHNK) Complication of DM

More common in Type II DM

High mortality

CHARACTERISTICS:
o *Extremely high glucose levels (>600mg/dl)
o Hyperosmolarity
o Osmotic diuresis (d/t hyperglycemia)
o Dehydration
o *Absence of ketones!! [differentiates btwn DKA (+ketones) and HHNK]

PRECIPITATING FACTORS:
o Stress
o Extensive burns
o Infection
o Myocardial infarction
o TPN or enteral feedings
o Glucocorticoids
o Thiazide diuretics

MANIFESTATIONS:
o *No metabolic acidosis, no ketones
o Polyuria
o Weakness

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Patho Wk 7: Endocrine

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Obtundation
Dehydration
Serum osmolality >310 mOsm/kg
Elevated hematocrit (hyperosmolar state)
*HypoK+
Hypophosphatemia

TREATMENT Rehydrate!
o Normal saline for the first hour
o 1/2 normal saline
o D5W when the blood glucose between 250 to 300 mg/dl
o Regular insulin
o Treat the underlying cause

LONG-TERM COMPLICATIONS OF DIABETES TYPE 1 AND 2

Retinopathy (leading cause of blindness = diabetes)

Nephropathy (leading cause of ESRD = diabetes, 2nd leading cause = HTN)

Neuropathy, PVD, Arterial insufficiency (leading cause of non-traumatic amputations = diabetes)

o Cant feel their extremities, nerve damage, dec blood flow

Gastropathy N/V

Myocardial infarction

CVA/stroke

d susceptibility to infection

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