Internal Medicine Flashcards
How to differentiate between primary hyperparathyroidism and familial hyperparathyroid syndromes?
Urinary calcium excretion (24-hour urinary calcium or calcium-to-creatinine ratio) should be measured to differentiate between familial hypocalciuric hypercalcemia
In your approach to the etiology of hypercalcemia what should you measure first?
PTH for PTH mediated hypercalcemia:
o Elevated - Primary hyperparathyroidism - Excess PTH from autonomous benign adenomas
o Mid- upper normal - Primary hyperparathyroidism likely or familial hyperparathyroid syndromes.
o Low-normal low (non-PTH mediated hypercalcemia)
What do tumors make that are not measured by PTH assays?
PTH-RP
____ have 1-alpha hydroxylase and convert 25 (OH)-vit. D3 to 1,25 (OH)2 D3 to increase calcium absorption in gut.
Granulomas (sarcoidosis, TB)
In patients with elevated 1,25-dihydroxyvitamin D3, what should be ordered?
Chest radiograph
The presence of low serum levels of PTH, PTHrp, and low or normal vitamin D metabolites suggests some other source for the hypercalcemia, name them.
- Immobilization – disturbance of resorption/formation balance
- Recovery phase of acute renal failure - Acute release of Ca++ from soft tissue deposits
- Thiazide diuretics
Labs for hypercalcemia?
Ionized calcium, calcium, phosphorus, chloride, and PTH levels + PTH-RP, lytes (r/o renal disease), 24hr urine calcium (r/o FHH), vitamin D (r/o vitamin D deficiency), albumin (r.o albumin deficiency)
How do you calculate a corrected calcium?
Get a corrected calcium – calcium is 40% protein bound. A simple formula to correct the serum calcium for albumin is: add 0.2 mmol/L to serum Ca++ for every 10 grams of albumin below 37 g/L
Imaging for hypercalcemia?
Imaging: neck/thyroid U/S, sestamibi scan (99mTc scan), CT scan
Treatment in acute hypercalcemia?
- Increase Urinary Ca2+ Excretion: FLUID, FLUID, FLUID! Isotonic saline (4-5 L) over 24 h ± loop diuretic (e.g. furosemide but only if hypervolemic (urine output >200mL/h). Calcitonin
- Decrease GI Ca2+ Absorption - Corticosteroids are potent inhibitors of 1a-hydroxylase
- Diminish Bone Resorption - bisphosphonates
Treatment of last resort for acute hypercalcemia and when is it indicated?
Indication: severe malignancy-associated hypercalcemia and renal insufficiency or heart failure
Treatment in chronic hypercalcemia?
Oral bisphosphonates protect bone from progressive calcium loss but do not decrease serum calcium levels.
What is primary hyperparathyroidism?
Primary Hyperparathyroidism: Elevated PTH level or serum calcium OR high normal PTH level in the setting of elevated serum calcium
Etiology of primary hyperparathyroidism?
Etiology: 80-90% have parathyroid adenoma, 10-20% have parathyroid hyperplasia, less than 1% have carcinoma
Initial medical treatment of hypercalcemia (1° HPTH)
Medical—IV NS fluids, furosemide & parathyroidectomy. In acute settings: bisphosphonates and prednisone
Treatment of parathyroid hyperplasia?
Neck exploration removing all parathyroid glands and leaving at least 30 mg of parathyroid tissue placed in the forearm muscles (nondominant arm, of course!)
Treatment of parathyroid adenoma?
Surgically remove adenoma (send for frozen section) and biopsy all abnormally enlarged parathyroid glands (some experts biopsy all glands)
What is secondary hyperparathyroidism?
Increased overall PTH production from calcium wasting caused by renal failure or decreased GI calcium absorption, rickets or osteomalacia; calcium levels are usually low
Etiology of secondary hyperparathyroidism?
Etiology: severe renal disease or low vitamin D levels
Why does renal disease cause hypercalcemia?
The failing kidneys are unable to reabsorb calcium (↓ CA) and unable to excrete phosphorous, which accumulates (↑ PHOS). Renal failure also leads to decreased conversion of 25-vitamin D to 1,25- vitamin D (decreased production of 1 alpha hydroxylase), which further decreases calcium absorption in the gastrointestinal tract.
Management of secondary hyperparathyroidism?
Management: Correct calcium and phosphate. If not on dialysis – vitamin D supplementation. If on dialysis then calcimimetrics or phosphate binders – subtotal parathyroidectomy if doesn’t respond to medical therapy
What is tertiary hyperparathyroidism?
Autonomous PTH production not responsive to the normal negative feedback due to elevated Ca2+ levels
Etiology of tertiary hyperparathyroidism?
Etiology: long term secondary hyperparathyroidism or renal transplant
Management of tertiary hyperparathyroidism?
Management: parathyroidectomy
Risk factors of hyperparathyroidism
Risk Factors: prior cancer, radiation exposure, renal disease, vitamin D deficiency, medications (calcium, lithium, thiazides), FHx, MEN-I and MEN-IIa
MEN1
Hyperparathyroidism, pituitary adenoma, pancreas neuroendocrine tumors
MEN2A
Medullary thyroid cancer, hyperparathyroidism, pheochromocytoma
Indications for parathyroidectomy
Symptomatic primary hyperparathyroidism due to effects of PTH on bone or kidneys, asymptomatic primary hyperparathyroidism with specific lab criteria
Lab Criteria: elevated Ca2+, marked hypercalciuria, Cr clearance <30% normal, bone density reduction with T score <2.5, <50 years old
Contraindications for parathyroidectomy
Familial hypocalciuric hyperkalemia
Complications of parathyroidectomy?
Recurrent/superior laryngeal nerve injury (hoarseness), post-operative hypocalcaemia (perioral numbness or numbness in fingers or toes, Chvostek sign), infection, bleeding
What is hungry bone syndrome?
Hungry bone syndrome is the constellation of hypocalcemia, hypophosphatemia, and hypomagnesemia after successful parathyroidectomy due to the sudden withdrawal of excess PTH
Definition of hypocalcemia?
Definition: total corrected serum Ca2+ <2.2 mmol/L
Symptoms and signs for hypocalcemia?
- Hypocalcemia is frequently asymptomatic.
- Paresthesias: perioral, hands, and feet
- Hyperreflexia
- ECG changes
- Tetany
- Laryngospasm (with stridor)
- Chvostek’s sign
- Trousseau’s sign
Tetany is a hallmark of hypocalcemia
- Sensory symptoms consisting of paresthesias of the lips, tongue, fingers, and feet
- Carpopedal spasm, which may be prolonged and painful
- Generalized muscle aching
- Spasm of facial musculature
What is Chvostek’s sign?
Chvostek’s sign is a twitching of the facial muscles
What is Trousseau’s sign?
Trousseau’s sign is carpal muscle spasm caused by obstruction to blood flow to the arm by a blood pressure cuff (kept at above systolic pressure for at least two minutes).
Initial investigations of hypocalcemia?
Initial investigations: PTH, PO43-, Mg2+, Urine Ca2+, creatinine
4 main categories of causes of hypocalcemia?
- Loss of calcium from the circulation
- Decreased vitamin D production or action
- Decreased parathyroid hormone production or action
- Low magnesium
Ddx for loss of calcium from the circulation
- Hyperphosphatemia (e.g., renal insufficiency)
- Pancreatitis
- Radiocontrast agents (EDTA)
- Osteoblastic metastases
- Rhabdomyolysis
Ddx for decreased vitamin D production or action
- Kidney injury
- Rickets
- Malabsorption
- Neonatal
- Alterations in vitamin D metabolism as occur with certain drugs (eg, phenytoin, phenobarbital, rifampin)
- Lack of sunlight
How does pancreatitis cause hypocalcemia?
When lipolytic products released from the inflamed pancreas chelate calcium
What is rickets?
Mutation in the gene encoding the 1-alpha-hydroxylase enzyme - needed to convert inactive vitamin D to the active form calcitriol
Hypoparathyroidism is characterized by ____ and _____
Hypoparathyroidism is characterized by hypocalcemia and hyperphosphatemia
What else should you treat concurrently with hypocalcemia?
Treat concurrent hypomagnesemia
Treatment of mild and symptomatic hypocalcemia? (ionized Ca2+ >0.8 mmol/L)?
- Calcium supplementation - 1500-2000 mg of elemental calcium/d
- Calcitriol 0.25 μg/d (especially in renal failure or hypoparathyroidism)
Treatment of acute or symptomatic hypocalcemia (ionized Ca2+ <0.7 mmol/L)?
IV calcium gluconate 1-2g over 10-20 min followed by slow infusion for tetany
If PTH recovery not expected in hypocalcemia, what is the treatment?
Requires long-term therapy with calcitriol and calcium •
Should you treat asymptomatic hypocalcemia?
No
Definition of fever?
Oral temperature >38.3°C
Definition of fever of unknown origin?
>38.3°C for > 3 wks duration
Fever in children under 2 must be a ____ temperature for accuracy
Rectal
Fever DDx
- Infectious causes
- Upper and lower respiratory tract infections
- Gastrointestinal infections
- Urinary tract infections
- Meningitis
- Endocarditis
- Skin infections
- Bacteremia - Malignant: leukemia, lymphoma, myelodysplastic syndromes, metastatic cancer
- Autoimmune and inflammatory disorders
- Vasculitis, RA
- IBD, sarcoidosis
- Endocrine (thyroid disease) - Post-surgical
- Allergic reaction, EtOH withdrawal, transfusion reaction
- Drug induced: overdose or side effect
- Environmental: heat stroke
Hyperthermia DDx
- Drugs (e.g.atropine)
- Blood transfusion reaction
- Infection/sepsis
- Medical disorder (e.g.thyrotoxicosis)
- Malignant hyperthermia
Fever occurs when the body’s _____ (located in the hypothalamus) resets at a higher temperature, primarily in response to an infection. Elevated body temperature that is not caused by a resetting of the temperature set point is called _____.
Thermostat
Hyperthermia
The cause of an acute (ie, duration ≤ 4 days) fever in adults is highly likely to be ____. When patients present with fever due to a noninfectious cause, the fever is almost always _____.
Infectious
Chronic or recurrent
Investigations for fever?
- CBC and differential, blood culture, urine culture, urinalysis, pregnancy test
- Venous gas (acidosis for sepsis)
- Stool O&P, C.dif, Gramstain, culture, monospot
- CRP
- PT/PTT
- LFT, TSH
- Electrolytes with blood urea nitrogen (BUN) and creatinine
- CXR, Mantoux skin test, sputum culture
- Lumbar puncture
A low WBC count may be just as worrisome as a high one; the WBC count may not be elevated in ______ in the presence of a serious infection. Overwhelming infection can cause bone marrow suppression and a reduced WBC, which may be manifest before the presence of hemodynamic compromise. Many indolent infections may not be associated with elevations in the WBC count.
Alcoholic patients, the older adult patients, HIV-infected patients, and other immunocompromised patients
Management of fever?
- ABCDEs and GCS, IV fluids, O2
- Broad spectrum IV abx if sepsis is suspected
- If temperature is ≥ 41° C, other cooling measures (sponge bath)
- Treat underlying disease
- Drugs:
- Acetaminophen 650 to 1000 mg orally every 6 hours
- Ibuprofen 400 to 600 mg orally every 6 hours
Definition of malignant hyperthermia?
Hypermetabolic disorder of skeletal muscle
Pathophysiology of malignant hyperthermia?
Due to an uncontrolled increase in intracellular Ca2+ (because of an anomaly of the ryanodine receptor which regulates Ca2+ channel in the sarcoplasmic reticulum of skeletal muscle)
Anesthetic drugs triggering malignant hyperthermia include:
- All inhalational agents except nitrous oxide
- Depolarizing muscle relaxants: SCh
Clinical features of malignant hyperthermia?
- Onset: immediate or hours after contact with trigger agent
- increased oxygen consumption
- increased ETCO2 on capnograph
- tachycardia/dysrhythmia
- tachypnea/cyanosis
- diaphoresis
- hypertension
- increased temperature (late sign) - Muscular symptoms
- trismus (masseter spasm) common but not specific for MH (occurs in 1% of children given SCh with halothane anesthesia)
- tender, swollen muscles due to rhabdomyolysis
- trunk or total body rigidity
Clinical features of malignant hyperthermia?
- Non-specific malaise, headache, fatigue
- Body temp <40.5oC (usually normal) No coma or seizures
- Dehydration (HR, orthostatic hypotension)
Treatment of malignant hyperthermia?
- Rest in a cool environment
- IV NS if orthostatic hypotension; otherwise replace losses slowly PO
What is “water depletion” in heat exhaustion?
Heat exhaustion occurs if lost fluid not adequately replaced
What is “salt depletion” in heat exhaustion?
Heat exhaustion occurs when losses replaced with hypotonic fluid
Heatstroke is differentiated from heat exhaustion by presence of the following?
- CNS dysfunction
- Temperature > 40C
Clinical features of classical heat stroke?
- Occurs in setting of high ambient temperatures (e.g. heat wave, poor ventilation)
- Often patients are older, poor, and sedentary or immobile
- Dry, hot skin
- Temp usually >40.5oC
- Altered mental status, seizures, delirium, or coma
- May have elevated AST, ALT
Clinical features of exertional heat stroke?
- Occurs with high endogenous heat production (e.g. exercise) that overwhelms homeostatic mechanisms
- Patients often younger, more active Skin often diaphoretic
- Other features as for classical heat stroke, but may also have DIC, acute renal failure, rhabdomyolysis, marked lactic acidosis
Treatment of heat stroke?
- Cool body temperature with water mist (e.g. spray bottle) and standing fans
- Ice water immersion also effective; monitor body temperature closely to avoid hypothermic overshoot
- Secure airway because of seizure and aspiration risk
- Give fluid resuscitation if still hypotensive after above therapy
- Avoid β-agonists (e.g. epinephrine), peripheral vasoconstriction, and antipyretics (e.g. ASA)
