Diagnosis

Hypocalcemia

Etiology

Causes of hypocalcemia [d8c][f14][pnq]

1. Hypoparathyroidism: PTH Deficiency 

   • Primary hypoparathyroidism

   • Iatrogenic: Post-radiation or post-parathyroidectomy

   • Magnesium depletion/excess

   • Autoimmune: Isolated or Autoimmune polyendocrine syndrome type 1

   • Neonatal: Maternal hyperparathyroidism or maternal FHH

   • Genetic: DiGeorge Syndrome, HDR syndrome, HRD syndrome, Mitochondrial gene defects

   • Infiltrative/Destructive Diseases: Metastatic carcinoma, Wilson's disease, Hemochromatosis, sarcoidosis, amyloidosis, thalassemia (iron overload due to transfusion)

2. High PTH Levels:

   • Vitamin D deficiency:

     • Nutritional deficiency

     • Lack of sunlight exposure

     • Malabsorption /gastric bypass surgery

     • Liver disease/cirrhosis

     • Chronic kidney disease

     • Inherited Disorders of Vitamin D production: rickets

   • PTH resistance (pseudohypoparathyroidism)

   • Renal failure (phosphate retention --> hypocalcemia)

3. Hyperphosphatemia (enemas, oral supplements, tumor lysis, crush injury, rhabdomyolysis) can lower calcium

4. Hypomagnesemia (in turn causes hypocalcemia)

5. Hypoalbuminemia (cirrhosis, nephrosis, malnutrition, burns, chronic illness, sepsis)

6. Acidosis/alkalosis

7. Drugs: Bisphosphonate, denosumab, Foscarnet

8. Blood transfusion

9. Acute pancreatitis

10. Necrotizing fasciitis

11. Sepsis/critical illness/trauma

12. Massive blood transfusion

13. Fistula

14. Post-thyroidectomy

Pathophysiology [pnq]

1. Calsium:

   • ~45% is bound to plasma proteins, primarily albumin

   • ~15% is bound to small anions such as phosphate and citrate

   • ~40% is in the free or ionized state

2. Corrected calcium in mmol/L:

   • 0.8 (Normal Albumin - Observed Albumin) + Observed Calcium

   • Measured calcium + ([40 - albumin (g/L)] × 0.02)

3. Hormonal regulators: Negative feedback loop

   • PTH increases calcium levels by increasing osteoclastic activity

   • Calcitonin lowers calsium levels by inhibition of osteoclasts

   • Calcium and activated vitamin D decrease PTH secretion

   • Elevated phosphorus levels increase PTH secretion

4. Calcium is vital for many body functions:

   • Cell function, nerve transmission, bone structure, intracellular signaling, and blood coagulation

Complications [pnq]

• Seizure

• Arrhythmia

Epidemiology

Prevalence per 100.000 [ok4][e4r][4nn][fco][bts]

Approach

• Blood test: calcium, phosphate, magnesium, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels

• Blood gas

• ECG

• EEG

• Echocardiography

Treatment

Treatment of hypocalcemia depends on severity and chronicity: [f14][pnq]

1. Acute symptomatic hypocalcemia --> Urgent treatment:

   • Calcium gluconate 2 g infusion: equivalent to 180 mg calcium diluted in 50 mL of 5% dextrose is infused over 10 minutes

   • Rapid administration could result in arrhythmias so intravenous administration should be carefully monitored

2. Correction of hypomagnesemia must occur to overcome PTH resistance before serum calcium will return to normal

3. Chronic asymptomatic hypocalcemia --> Oral therapy:

   • Calcium carbonate 1-3 grams

   • Calcitriol (the active metabolite of vitamin D)

   • Thiazide diuretics can increase renal calcium reabsorption in patients with hypoparathyroidism

   • Recombinant human parathyroid hormone if chronic hypoparathyroidism

4. Disease-specific treatment:

   • Postsurgical hypoparathyroidism

   • Hypomagnesemia

   • Vitamin D deficiency

   • CKD

Differential diagnoses

Acute pancreatitis, Albuminuria, Clostridium tetani, Heart failure, Hemochromatosis, Hyperkalemia, Hyperparathyroidism, Hyperphosphatemia, Hyperventilation, Hypocalcemia, Hypocapnia, Hypokalemia, Hypomagnesemia, Hypoparathyroidism, Meningitis, Metabolic alkalosis, Milk-alkali syndrome, Neuroleptic malignant syndrome, Parkinson's disease, Renal failure, Sepsis, Stiff man syndrome, Wilson's disease