Hungry bone syndrome following parathyroidectomy 2011. 7. 6 Seo Mi Seon

Introduction Hypocalcemia common problem after parathyroidectomy or thyroidectomy cause functional or relative hypoparathyroidism → ↓bone reabsorption & intestinal calcium absorption ↑increased calcium excretion (not ESRD) acute calcitonin release from the thyroid gland generally transient degree of bone disease : mild normal parathyroid tissue recovers function quickly (usually within one week)

hungry bone syndrome postop. hypocalcemia → severe, prolonged (normal or ↑ PTH) m/c preop. bone disease (d/t 1’ or 2’ PTH ↑↑ (osteitis fibrosa) → bone resorption ↑) calcimimmetics similar syndrome reduce PTH secretion by modulating the calcium-sensing receptor in the parathyroid glands thyroidectomy (hyperthyroidism) preop. bone disease (d/t excess thyroid hormone → high bone turnover) estrogen Tx. meta. prostate ca.

PATHOGENESIS Hyperparathyroidism, high turnover state : PTH → ↑ bone formation(osteoblast) & ↑ resorption(osteoclast) → net efflux of ca from bone PTH sudden withdrawal → imbalance : bone formation ↔ bone resorption →↑ bone uptake of calcium, phosphate, magnesium abrupt decrease in PTH release : upsets the equilibrium calcium efflux from bone ↔ influx into the skeleton (bone remodeling)

metastatic prostate cancer treated with estrogen similar mechanisms osteoblastic metastases : calcium sink & bone resorption ↑ → maintain serum ca. ** Estrogen → ↓bone resorption → bone ca uptake↑

Hypocalcemia after parathyroidectomy 25 pt. 1’ hyperparathyroidism, parathyroidectomy, hungry bone syndrome most : first 24 hours after surgery Am J Med 1988; 84:654.

INCIDENCE 198 pt. (1’ hyperparathyroidism, parathyroidectomy) HBS : Ca < 8.5 mg/dl, P < 3.0 mg/dl (POD #3) → 13% Am J Med 1988; 84:654. 148 pt. (ESRD, dialysis, 2‘ hyperparathyroidism, parathyroidectomy) → 20% Kidney Int Suppl 2003; :S97.

Risk factors 1’ hyperparathyroidism resected adenoma volume Preop. BUN Preop. ALP older age not ca. & PTH ESRD, 2’ hyperparathyroidism : unclear postop. Ca ↓ preop. bone bx. specimen : bone disease severity Am J Med 1988; 84:654.

CLINICAL FEATURES largely due to hypocalcemia hypophosphatemia, hypomagnesemia, hyperkalemia Hypocalcemia nadir : 2-4 days postop. tetany, seizures major bone fractures over heart failure in latent myocardial dysfunction : cardiomegaly & pulmonary congestion resolved (← ca normalization) duration : variable (∼ 3M)

2. Hypophosphatemia  bone resorption↓ , bone formation ↑ 1’ rather than 2’ : 2’ → initially high level P → still normal range

Effects of parathyroidectomy in end-stage renal disease Arch Intern Med 1969;124:431. 11 uremic pt. (severe 2’ hyperparathyroidism, subtotal parathyroidectomy) Changes in total plasma calcium and phosphate

3. Hypomagnesemia 4. Hyperkalemia more prevalent in 1’ recognition and treatment : important : PTH secretion ↓ & PTH resistance → refractory hypocalcemia 4. Hyperkalemia 80% of dialysis pt. pathophysiology : unknown

TREATMENT Hypocalcemia ** careful monitoring : serum ca. : 2-4 times/day (first few days → greatest risk) oral calcium * 2 – 4g (50-100 mmol) elemental ca. /day (as soon as the patient is able to swallow) * serum phosphorus : normal or low → ca. : between meals (intestinal absorption ↑ & phosphate binding↓)

2) IV calcium Ix. 1-2g calcium gluconate (elemental ca. 90-180mg) + serum ca. : rapid & progressive reduction or symptoms (frank tetany, latent tetany (Chvostek's or Trousseau's sign)) plasma ca. < 7.5 mg/dL (1.9 mmol/L) 1-2g calcium gluconate (elemental ca. 90-180mg) + 5% dextrose 50mL (10-20min) : should not given more rapidly (risk of serious cardiac dysfunction (systolic arrest)) → raise ca. for only 2 or 3 hours → slow infusion of ca.

3) Infusion of calcium infusion solutions 10% calcium gluconate (90mg elemental ca./10mL) : preferred (less likely to cause tissue necrosis) 10% calcium chloride (270mg elemental ca./10mL) 1mg/mL of elemental calcium gluconate : 10% calcium gluconate 100mL + 5% dextrose 1000 mL (90mg elemental ca./10mL → total 900mg elemental ca.) → initial infusion rate 50mL/h (50mg/h) → dose can be adjusted (ca. : lower end of the normal range) ** 0.5 – 1.5mg/kg/hr elemental ca.

(form insoluble calcium salts) the calcium should be diluted in dextrose and water or saline (concentrated calcium solutions are irritating to veins) IV solution should not contain bicarbonate or phosphate (form insoluble calcium salts) → another intravenous line (in another limb) should be used

4) Vitamin D maintenance dialysis pt. (often vit.D deficient) placebo-controlled trial postop. oral calcitriol in doses up to 4 mcg/day → ameliorated the postop. decline in the serum calcium Nephron 1987; 46:18. oral & IV calcitriol relative efficacy : no studies common practice : calcitriol IV at increased doses

5) Dialysis another method of correcting the hypocalcemia Hemodialysis : high calcium bath (3.5meq/L, 1.75 mmol/L) IV calcium during dialysis PD (CAPD) : 1-3 ampules of calcium gluconate → each bag of PD

2. Hypomagnesemia and hypophosphatemia ** significant hypomagnesemia & hypophosphatemia can occur in 1’ hyperparathyroidism   1) Hypomagnesemia → PTH secretion↓ & PTH resistance → refractory hypocalcemia ** raising the serum magnesium → correction of the hypocalcemia

2) Hypophosphatemia administration of phosphate → generally avoided (phosphate can combine with calcium → reduce the plasma calcium) exception : severe hypophosphatemia (plasma phosphate < 1 mg.dL (0.32mmol/L) ** uncommon in CRF pt. (serum phosphate values are elevated → fall toward normal range after surgery)

3. Hyperkalemia serum potassium should be closely followed in ESRD dialysis on the first or second postop. day (preferably with a no-heparin protocol)

PREVENTION Vitamin D (calcitriol) HD pt. (vitamin D deficiency) preop. calcitriol Regimen : IV calcitriol 2mcg at the end of each HD Tx. begin 3-4 days prior to surgery continued postop. ↓bone remodeling & ↑ absorption of oral calcium → minimize the need for IV calcium postop. oral calcium 2-3g/d (2days prior surgery), even hypercalcemic Am J Kidney Dis 1997; 29:759.

Bisphosphonates few case reports and several retrospective studies : preoperative administration of bisphosphonates bisphosphonates were used to treat hypercalcemia in severe 1’ and 2’ hyperparathyroidism prior to parathyroidectomy Nephron 1996; 74:729. Nephrology (Carlton) 2007; 12:386.

bisphosphonates can reduce serum calcium → these paradoxical observations require confirmation with a controlled randomized study