HYPOCALCEMIA: Correct for Sodium for Albumin à 2/2 (see reference) à if in doubt check ionized calcium à iPTH, Magnesium, Vitamin D (25-OH), check 1,25-OH Vitamin D only if suspecting vitamin D deficiency or CKD à Rx:a. If symptomatic, and severe: IV SLOW infusion of Calcium Gluconate (0.5-1.5 mg elemental calcium/kg/h); switch to oral once symptoms have resolved b. If asymptomatic, and mild: Oral is okay (see reference) Reference: 1. Differential Diagnosis of Hypocalcemia (MKSAP Endo Table 30)2. Treatment with Oral Hypoglycemia (MKSAP Endo Table 31) HYPERCALCEMIA: rule out factitious hypercalcemia (check iCa++ under anaerobic conditions, and in ice) - Once True Hypercalcemia confirmed - check iPTH and iCa++ simultaneously - check PO43- and Vitamin D - DDx. 2/2 (MKSAP Table) based on if PTH is high or low - Asymptomatic or Symptomatic due to prolonged or severe disease (Nephrolithiasis, CKD, fragility fractures, bony pain)
- Treatment:
- Short-term interventions based on mild, moderate or severe hypercalcemia: IV Fluid, Furosemide, IV Bisphosphonate, SC Calcitonin, Denosumab (off-lable in CKD patients), Glucocorticoids (if increased intestinal calcium absorption)
- Longterm treatment based on cause
- Pathophysiological Classification of Hypercalcemia
- Humoral Process
- PTH - via Bone and via Vitamin D via Gut
- TSH
- PTHrp
- VItaminD
- Source of Hypercalcemia
- GI (Vitamin D, Milk Alkali, Hyperpara via Vitamin D)
- Kidney
- Bone (Malignancy, Immobilization, Vitamin D, TSH)
- Hormonal Axis
- Calcium - PTH - 2 end-organ
- Bone : Multiple actions in bone
- Direct actions: Increase bone remodeling by increasing number of osteoclasts (do not have PTH receptors) and osteoblasts (have bone receptors) ( this action occurs within hrs)
- Continuous exposure: Bone resorption
- Intermittent exposure (few hrs a day): Net effect is bone formation
- Indirect actions: PTH mediated action on osteoclast is indirect via cytokines released from osteoblasts
- 3 effect in Kidney
- Ca reabsorption: Distal tubule,
- PO43- excretion: Proximal tubule,
- Increase 1,25 Vitamin D)
- 25, OH Vitamin D - Increase PTH, and Low PO43- will increase 1, 25 OH - 3 target organ
- Gut (Increase PO43- and Ca2+)
- Bone (Resorption at high level, deposition at normal level)
- Effect on Kidney is questionable
 - Understanding The Mechanism:
- Calcitonin: (Harrisons 91 e)
- hypocalcemic activity of calcitonin: is accounted for primarily by inhibition of osteoclast-mediated bone resorption and secondarily by stimulation of renal calcium clearance. These effects are mediated by receptors on osteoclasts and renal tubular cells.
- Additional effects are through receptors present in the brain, the gastrointestinal tract, and the immune system
- Osteoblast and Osteoclast maturation pathways
- Vitamin A mediated Hypercalcemia:
- ATRA inhibits cell growth by down regulation of IL-6 R. Subsequent increase in IL 6 activates osteoclasts. See Harrison's for how osteoclasts are activated.
- Multiple Myeloma , other malignancy and Hypercalcemia: IL-1 or TNF mediated osteoclast activation
- Rhabdomyolysis and Acute Renal Failure: Due to mobilization of Ca++ present in the muscles; Increased PO43- leads to increased PTH - leads to increased Ca2+; Unexplained mechanism leads to increased Vit D which in turn leads to increased Ca absorption.
- Li : Increased in the set point at which Ca++ suppresses PTH, which leads to increased PTH release and increase in Calcium level
- PTH mediated Hypercalcemia: Will have low Phosphorous, and high Cl, with ratio > 33.
Reference: Etiology of Hypercalcemia (MKSAP Nephro Table 27)Clinical manifestations of hypercalcemia UpToDateDiagnostic approach to hypercalcemia UpToDate
Hypercalcemia:Case 4-2011 (4 yr old Child)
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