Hypo/Hypercalcemia

• Role of calcium

  • neuromuscular signaling

  • cardiac contractility

  • hormone secretion

• Extracellular calcium concentrations are maintained by

  • parathyroid hormone

  • Vitamin D metabolite

  • 1,25- dihydroxyvitamin

HYPERCALCEMIA

• Hypercalcemia - causes can be understood and classified based on derangements in the normal feedback mechanisms that regulate serum calcium

• Clinical Manifestation of Hypercalcemia

  • decrease renal concentrating ability (polyuria and polydipsia)

  • long-standing hyperparathyroidism (bone pain or pathologic fracture)

  • ECG changes (bradycardia, AV block, short QT interval)

• Excessive PTH production causes

  • Primary hyperparathyroidism (adenoma, hyperplasia, rarely carcinoma)

  • Tertiary hyperparathyroidism (long-term stimulation of PTH secretion in renal insufficiency)

  • Ectopic PTH secretion

  • FFH (familial hypocalceuuric hypercalemia)

  • Alterations in CaSR function (lithium therapy)

• Mild hypercalcemia - serum calcium level of 11-11.5 and is usually asymptomatic

• Clinical manifestation of Mild hypercalcemia

  • in mild cases (vague neuropsychiatric symptoms, trouble concentrating, personality changes, depression)

  • other presenting symptoms (peptic ulcer disease or nephrolithiasis, fracture risk)

• Severe hypercalcemia - serum calcium level of >12 to 13

• Clinical symptoms of severe hypercalcemia

  • when develops acutely ( lethargy, stupor, coma, gastrointestinal symptoms)

• Chronic hypercalcemia - most commonly caused by primary hyperthyroidism

• First step in diagnostic evaluation of hyper/hypocalcemia

  • to ensure that the alteration in serum calcium level is not due to abnormal albumin concentration

• Evaluation of PTH level - second most important laboratory test in diagnostic evaluation of hypercalcemia

• Initial therapy of significant hypercalcemia

  • volume expansion (4-6 L of IV for 24hrs)

  • loop diuretics (use to enhance sodium and calcium excretion)

  • salmon calcitonin (drug that inhibit calcium resorption)

  • biphosphonates and denosumab (potent inhibitor of bone resorption)

  • zoledronic acid and pamidronate (used for hypercalcemia of malignancy in adult)

  • gallium nitrate (alternative for biphosphonate and denosumab but has potential nephrotoxicity)

  • dialysis ( for rare cases)

  • glucocorticoids (for patient with 1,25 D-mediated hypercalcemia)

HYPOCALCEMIA

• Most common etiologies of hypocalcemia - impaired PTH production and impaired Vitamin D production

• Hypoparathyroidism - cardinal feature of autoimmune endocrinopathies and associated with sarcoidosis

• Impaired PTH production - due to magnesium deficiency or activating mutations in CaSR or in G proteins that mediate CaSR signaling

• Vitamin D deficiency - due to impaired 1,25 D production or vitamin D resistance

• Hypocalcemia may also occur in - severe tissue injury such as burns, rhabdomyolysis, tumor lysis or pancreatitis

• Clinical manifestation of moderate to severe hypocalcemia

  • paresthesias (usually of fingers, toes, circumoral regions, increase neuromuscular irritability)

  • chvostek’s sign ( twitching of the circumoral muscles in response to gentle tapping of the facial nerve just anterior to the ear)

  • trousseau’s sign (carpal spasm induced by inflation of blood pressure cuff to 20 mmHg)

• Clinical manifestation of severe hypocalcemia

  • seizures

  • carpopedal spasm

  • bronchospasm

  • laryngospasm

  • prolongation of QT interval

• Diagnostic approach in evaluation of hypercalcemia

  • measuring calcium levels

  • albumin, phosphorus and magnesium levels

• Determining of PTH level - central for evaluation of hypocalcemia

• Management in acute, symptomatic hypocalcemia

  • calcium gluconate

  • magnesium supplementation ( accompanied with hypomagnesemia)

• Management in chronic hypocalcemia due to hypoparathyroidism

  • calcium supplements

  • vitamin d2/d3 or calcitriol

• Treatment of refractory hypoparathyroidism

  • PTH (1-84) (Natpara)

• Management in Vitamin D deficiency

  • vitamin D supplementation

• Treatment goal of hypocalcemia

  • to bring serum calcium into low normal range

  • to avoid hypercalciuria which may lead to nephrolithiasis

• Global consideration

  • Primary hyperparathyroidism - often present with severe form of skeletal complications (osteitis fibrosa cystica)

  • Vitamin D deficiency - common in countries despite extensive sunlight (india) due to avoidance of sun exposure and poor dietary vit. d intake