Endocrinology Flashcards
(47 cards)
Hypoglycemia
Glucose is the sole energy source for the brain
Symptoms of hypoglycemia depend on the glucose level and the rate of glucose drop
Hypoglycemia can mimic stroke, TIA, epilepsy, MS, psychosis, Stokes-Adams
Counterregulatory hormones (glucagon and epinephrine) cause the release of glycogen from the liver
Sympathomimetic symptoms: sweating, tremor, pallor (vasoconstriction), anxiety, nausea
Sympathomimetic symptoms can be masked by beta blockers
Neuroglycopenia symptoms: dizziness, psychosis, confusion, coma
Differential diagnosis
Insulinoma
Medications / drugs / alcohol
Extrapancreatic neoplasm
Hepatic disease (depletion of glycogen stores)
Deficiency of counterregulatory hormones
Critically ill, stressed infants, hypothermia
Dumping syndrome
Artifactual
Continued glycolysis by WBCs in lab tube
Leukemia, polycythemia
Distinguishing excess endogenous insulin from excess exogenous insulin
Pancreas cleaves proinsulin to insulin plus immunoreactive C-peptide
Excess endogenous insulin has measurable C-peptide (not so with excess exogenous insulin)
Standard treatment options D50 D25 (peds) D10 (neonates) Glucagon 1 mg IM/IV (converts liver glycogen to glucose) D10 drip if recurrent or overdose Hydrocortisone (adrenal insufficiency) Octreotide – inhibits insulin secretion and helps prevent rebound hypoglycemia in the setting of glucose infusion treatment of refractory sulfonylurea-induced hypoglycemia
Oral Agents In DiabTwo classes: hypoglycemics & antihyperglycemics Hypoglycemic agents: Sulfonylurea agents Chlorpropamide, tolbutamide, acetohexamide tolazamide, glipizide, glyburide, glimepiride Stimulate pancreatic insulin secretion Cause profound hypoglycemia in overdose Long duration of action Chlorpropamide also can cause SIADH Repaglinide (Prandin) Can also cause hypoglycemia Antihyperglycemic agents Less likely to cause hypoglycemia in overdose Metformin May cause lactic acidosis (uncommon) Alpha-glucosidase inhibitors Inhibit intestinal hydrolysis of polysacharides Oral sucrose will not be absorbed Thiazolodenediones (Avandia/Actos) Can worsen CHF; Acute MI (Avandia) SGLT2 inhibitors Increases renal secretion of glucose Hypotension (osmotic diuresis)
Always admit if sulfonylurea overdose
Most symptomatic in 4 hours (can be delayed)
Octreotide inhibits insulin secretion
Give thiamine with glucose in hypoglycemic malnourished patients
Glucagon may not be effective in chronic alcoholics, those with liver disease or infants with low, liver glycogen stores
Diabetic Ketoacidosis Pathophysiology
Relative lack of insulin + stressors causes hyperglycemia
Hyperglycemia-induced osmotic diuresis causes polyuria, dehydration, hypovolemia, electrolyte loss (K, Mg, Phos)
Switch over to fat breakdown for energy source causes ketonemia (acidosis)
Metabolic acidosis causes compensatory hyperventilation (Kussmaul respirations)
Precipitants of DKA
The “I’s” have it! Infection (UTI, pneumonia, pancreatitis) Infarction (e.g. AMI) Insulin noncompliance IUP (pregnancy) Ischemia (CVA) Illegal (substance abuse) Iatrogenic (drug interactions) Idiopathic (new onset DM)
Fluids / Bicarbonate in DKA
Initial fluid resuscitation for hypovolemia
Replace electrolytes (phosphate, potassium)
Insulin drip (after checking potassium)
Sodium bicarbonate is rarely indicated
The hazards of bicarbonate use include
Paradoxical CSF acidosis
Decreased oxygen-hemoglobin dissociation (shifts curve to left)
Overload of sodium
Hypokalemia, hypophosphatemia
Cerebral edema in children
Sodium / Phosphate in DKA
Pseudohyponatremia
(*Hyperosmolar as opposed to hypoosmolar state)
Sodium is artifactually 1.6 mEq/L for every 100 mg/dL glucose over 100
Hypophosphatemia is possible:
Respiratory depression, muscle weakness
CHF, decreased mental status
(failure to generate adequate ATP)
Potassium in DKA
Serum K+ level may be elevated, normal or low
Initial hypokalemia indicates massive total body depletion (usual deficit is 3-7 mEq/L)
Replacement recommendations
K < 3.3: Hold insulin, give 40 mEq per hour until ≥ 3.3
K ≥ 3.3 but < 5.0: give 20-30 mEq in each liter IVF to keep K 4-5 mEq/L
K ≥ 5.0: No replacement but check Q2 hr
Serum potassium will decline with insulin and correction of acidosis (drives K+ into cells)
Cardiac arrest in DKA is often 2° to precipitous hypokalemia (insulin therapy, acidosis correction or fluid therapy with increased urinary losses)
Complications of DKA Treatment
Hypoglycemia due to excess insulin Add glucose administration when glucose = 250 mg/dl Hypokalemia is associated with insulin administration, bicarbonate, hydration Bicarbonate therapy causes CSF acidosis Cerebral edema Patients at risk: Young, new onset DM Etiology controversial Avoid bicarbonate in children
Alcoholic Ketoacidosis
Binge drinking with heavy alcohol consumption and decreased food intake for several days (starvation ketosis)
Imbalance of insulin levels and counter- regulatory hormones
Ethanol metabolism inhibits gluconeogenesis
Abdominal pain, nausea, vomiting, dehydration, disorientation
Alcohol levels are usually low or negative and glucose is often mildly elevated with low bicarbonate and high anion gap
Urinary ketones may be weakly positive
Treatment: Glucose + saline (D5NS), thiamine and potassium repletion
The major and earliest ketone produced from fat
breakdown is beta-hydroxybutyrate, but the
lab-measured ketone is acetoacetate.
Therefore, lab tests for
ketones may be falsely negative.
Hyperosmolar Hyperglycemic Non-ketotic State HHNS (1)
Similar to DKA but has important distinctions
No ketoacidosis
Glucose is usually higher, often >1000
Serum osmolality is often greater than 350
Most often occurs with NIDDM
Higher mortality than DKA
DKA has shorter onset
Precipitating factors include Infection, especially pneumonia Myocardial infarction CVA GI bleed Pyelonephritis Pancreatitis Uremia Subdural hematoma Peripheral vascular occlusion
Common comorbid conditions
Renal insufficiency
Vascular disease
Poor access to water
HHNS is often the initial presentation of NIDDM
Common associated medications Diuretics Propranolol Calcium channel blockers Corticosteroids Phenytoin Cimetidine
Hyperosmolar Hyperglycemic Non-ketotic State HHNS
Physical findings Dehydration Altered sensorium Focal neurologic findings (often mistaken for a stroke) Coma is rare
Treatment
Normal saline
Average fluid deficit 8-12 liters
½ of deficit in first 12 hours, rest over next 24 hours
Initial 1-2 liter bolus as clinically indicated
Insulin infusion
Cerebral edema possibly 2° to rapid fluid replacement or the severity of the condition
Thyroid Hormones
TRH from hypothalamus stimulates TSH release from anterior pituitary
TSH stimulates thyroid gland
Thyroid hormones (T3, [20%]T4 [80%]) are synthesized and released
Thyroid hormone production depends on iodine intake. Excess iodine blocks hormone release
T3 is biologically 4x more active than T4
T3 and T4 provide feedback inhibition of TSH release
T3 and T4 act on cells
Increase rate of cell metabolism
Increase rate of protein synthesis
Hyperthyroidism
Causes
Graves’ disease (most common):
An autoimmune disorder (thyroid-stimulating immunoglobulins mimic the action of TSH)
Toxic thyroid adenoma, toxic multi-nodular goiter
Thyroiditis
Pituitary adenoma
Excess iodine in diet
Hyperthyroidism
Signs and symptoms Nervousness, tremor, insomnia Heat intolerance, sweating Weakness, weight loss, hair loss Tachycardia, palpitations Hyperdefecation Irregular menses Goiter / thyroid bruit Exopthalmos (Grave’s only), lid lag (the lids move more slowly than the eyes)
Hyperthyroidism (3) Pre-tibial Myxedema
Rare manifestation of Graves’ disease
Bilateral, elevated, firm dermal nodules and plaques
Skin yellow or waxy
Accumulation of mucopolysaccharides
Hyperthyroidism
Risk factors: female, family history, other autoimmune disease Lab: Increased T3 and T4, decreased TSH Treatment Beta blockers PTU or methimazole Radioactive iodine Surgery
Thyroid Storm
A life-threatening complication of hyperthyroidism. May not be directly related to magnitude of excess thyroid hormone Precipitating events include Withdrawal of antithyroid medications Administration of IV contrast Thyroid hormone overdose Pneumonia CVA Pulmonary embolus Toxemia of pregnancy Diabetes
Thyroid Storm
Thyroid storm is a clinical diagnosis
The hallmark is CNS dysfunction
Other diagnostic criteria include
Temperature > 38˚C
Tachycardia out of proportion to the fever
Exaggerated peripheral manifestations of thyrotoxicosis, including tremor and weakness
No laboratory tests distinguish thyroid storm from simple hyperthyroidism – it is a clinical diagnosis
Thyrotoxicosis / thyroid storm is associated with Elevated free T4 level Decreased TSH level Hyperglycemia Hypercalcemia Elevated LFTs Low cholesterol
Thyroid Storm Treatment
Five step ORDERED approach
- General supportive care: IV fluids, correct electrolyte imbalance, corticosteroids (decrease peripheral conversion of T4 to T3), no ASA (displaces thyroid hormone from thyroglobulin)
- Block peripheral thyroid hormone effects: Propranolol 1 mg to 10 mg titrated to symptoms
- Block thyroid hormone synthesis: PTU (also inhibits peripheral conversion of T4 to T3) or Methimazole
- Block thyroid hormone release: iodine given one hour after PTU
- Identification and treatment of precipitating events
Rare disorder seen in elderly patients
Lethargy, slowed mentation, apathetic facies
Goiter is usually present
Droopy eyelids are common
No exophthalmos, stare or lid lag
Symptoms of apathetic hyperthyroidism may be masked because of underlying organ dysfunction
Resting unexplained tachycardia
Resistant atrial fibrillation and CHF are common
Apathetic Thyrotoxicosis
Hypothyroidism
Causes
Treatment of Graves’ disease
Iodine deficiency in diet
Autoimmune destruction of thyroid gland (e.g. Hashimoto’s)
Lithium therapy for bipolar disorder
Amiodarone
Pituitary and hypothalamic disorders (rare)
Hypothyroidism
Signs and symptoms Weakness, lethargy Cold intolerance Hypothermia Weight gain Constipation Dry, thick skin Generalized nonpitting edema (myxedema) Prolonged, heavy periods
Hypothyroidism
Clinical signs of severe hypothyroidism include
Dermatologic: coarse, waxy skin, loss of lateral third of eyebrows, scant pubic hair, puffy face and extremities (myxedema)
CNS: slowed mentation, altered mental status, psychosis (“myxedema madness”), coma
Cardiac: CHF, bradycardia, hypotension, cardiomegaly, pericardial effusion, low voltage
Hypothyroidism
Lab Low T4, elevated TSH (unless problem with hypothalamus or pituitary) Elevated lipids Hyponatremia (dilutional) Anemia Myxedema coma Hypoxemia Hypothermia
Myxedema Coma
The end of the spectrum of hypothyroidism
Life-threatening, rare, elderly females, winter
Precipitating factors include
Stressors: MI, infections, trauma, cold exposure
Drugs are metabolized slower and therefore have increased effects (narcotics, tranquilizers, beta blockers, amiodarone)
Non-compliance with thyroid replacement
Myxedema Coma
Signs
Hypothermia
Altered mental status
“Hung up” reflexes (prolonged relaxation phase of DTRs)
Non-pitting periorbital edema (puffy eyelids)
Generalized non-pitting edema
Myxedema Coma
Treatment
Supportive care: Rewarming, fluid support, search for underlying cause
Specific treatment
IV thyroid hormone (T4, T3 or both)
Avoid excessive IV T3 (increased mortality)
Corticosteroids (because of possible
unrecognized adrenal or pituitary insufficiency)
b
Adrenal Gland
Clinical manifestations primarily due to
Cortisol (affects metabolism of most tissues, glucose regulation, increases blood glucose)
Aldosterone (renal Na+ reabsorption & K+ excretion)
b
Adrenal Insufficiency (1) Primary Adrenal Failure
Idiopathic (autoimmune):
Addison’s Disease
Infiltrative, infectious
Sarcoid, amyloid
TB, fungal, septicemia
Hemorrhage, infarction
Neoplastic
Drugs (etomidate)
Bilateral adrenal failure is associated with meningococcemia (Waterhouse-Friderichsen)
Presents with abdominal pain, vomiting, fever, hypotension
Diagnosis by serum cortisol level or corticotropin stimulation test
Hyperpigmentation is seen in
Addison’s disease
Adrenal Insufficiency
Secondary adrenal failure
Due to hypopituitarism
Tertiary adrenal failure
Usually iatrogenic from prolonged steroid use (most common cause overall)
Causes adrenal atrophy
Usually due to oral steroids (rarely inhaled or topical)
Laboratory abnormalities include
Hyponatremia (most common abnormality) +/- hyperkalemia, eosinophilia (all most common in chronic insufficiency), hypoglycemia
Acute presentation
Refractory hypotension
Non-specific symptoms: Fever/N/V/weakness/AMS
Consider in malignancy
Adrenal Crisis (Insufficiency)
Treatment Fluids – NS or D5NS Glucocorticoids – hydrocortisone 100 mg or dexamethasone 4 mg IV Pressors Mortality from adrenal crisis due to Shock Dysrhythmias (hyperkalemia) Underlying disease
Diabetes Insipidus
Symptoms similar to DM – excess urination and increased thirst and fluid intake
Lack of ADH activity
Central: Failure to secrete ADH (head trauma, neoplasm, pituitary surgery)
Nephrogenic: Kidney not responding to ADH (lithium toxicity, hypokalemia, hypercalcemia, nephrotoxic drugs)
Presents with polydipsia, polyuria
Lab: Dilute urine in the face of concentrated serum (hypernatremic and hyperosmolar)
Central DI will concentrate urine with ADH; nephrogenic DI will not respond
Treatment
Central = Desmopressin (synthetic vasopressin = DDAVP)
Nephrogenic = Hydrochlorothiazide
Hyperadrenalism (Cushing’s Syndrome)
Excess cortisol Prolonged steroid use (most common) Adrenal neoplasm, pituitary microadenoma ACTH-secreting carcinoma (small cell, pancreatic, bronchial carcinoid)
Signs and Symptoms
Truncal obesity, hypertension, hirsutism, edema, glucosuria, Na+
Moon facies, buffalo hump, purple striae
Treatment: Stop steroids, treat cause
Pheochromocytoma
Rare cause of treatable hypertension
Often diagnosed at autopsy
Can be malignant
Tumor of adrenal medulla cells (secretes norepinephrine)
Diagnosis: catecholamines and metabolites (VMA) in 24 hour urine
5 Ps (paroxysmal spells) in a 20-45 y/o patient
Pressure (sudden increased hypertension)
Pain (headache, chest pain, abdominal pain)
Perspiration
Palpitations
Pallor
Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Normally, ADH is secreted in states of dehydration
ADH increases renal H20 reabsorption
ADH is inhibited in over-hydration (dilutes urine)
SIADH: Inappropriate ADH secretion (inhibits urine production resulting in fluid retention and dilutional hyponatremia)
Inappropriately concentrated urine in the setting of low serum osmolality (low sodium) and normovolemia = SIADH
Causes include CNS (tumor, infection, CVA, injury), Lung (infection including TB, fungal), Drugs (chlorpropamide, vasopressin, diuretics, vincristine, thioridazine, cyclophosphamide)
Carcinoid Syndrome
Carcinoid tumor: GI tumors in small intestine, appendix, stomach, colon (can be in lung too)
Common with liver metastases
Tumor secretes serotonin, prostaglandins and other bioactive substances
Attacks of skin flushing, watery stools, hypotension, vasodilation, edema, ascites and bronchoconstriction
Attacks can last from minutes to days
Treat with somatostatin analogs (octreotide)
Usually due to too much water relative to sodium
Symptoms depend on level and rate of drop
Early: Nausea, headache
Late: Lethargy, seizures
Symptoms often start around 120 mEq/L
Hyponatremia
Hyperglycemia
Free water osmotically drawn out of cells and into serum, leading to lower serum Na+ (Remember Na+ drops 1.6 mEq/L for every 100 mg/dL increase in glucose over 100)
Hyperlipidemia, hyperproteinemia
Displaces sodium from the lab specimen
Pseudohyponatremia
Hyponatremia Treatment
Depends upon etiology, chronicity and severity
Hyponatremia that develops slowly should be corrected slowly
Hypovolemic hyponatremia
Replace fluid deficits with NS
100-150 mL/hr
Euvolemic hyponatremia
Correct underlying cause
Water restriction (+/- furosemide if Na+ < 120)
Hypervolemic hyponatremia
Goal is to increase Na+ and H2O loss
Salt and water restriction
Diuretics to increase Na+ loss
Caveat: May worsen hyponatremia because water leaves in excess of Na+
Faster correction: IV NS & loop diuretics (furosemide)
Hyponatremia Treatment
Life-threatening symptoms Severe hyponatremia (Na+ < 120 PLUS CNS abnormalities) Goal is to raise level to >120 mEq/L Rise in Na+ should be no greater than 0.5-1.0 mEq/L per hour (1-2 mEq/L per hour if seizures) Hypertonic saline (3%) 25-100 mL/hr Furosemide (Lasix) 20-40 mg IV Too-rapid correction CHF Central pontine myelinolysis (CPM)
Results from too rapid correction of hyponatremia
Occurs 24-48 hours after rapid correction
Symptoms include confusion progressing to cranial nerve deficits to quadriparesis to locked-in syndrome; dysphagia, dysarthria, paresis
Concomitant use of furosemide (Lasix) has been shown to decrease incidence of CPM
Central Pontine Myelinolysis
