Nephrology Grand Rounds 5/13/08

Refractory Hyperparathyroidism Brad Weaver

Causes of refractory HPTH Inadequate therapy Inadequate therapy Persistent hyperphosphatemia Persistent hyperphosphatemia Acquired abnormalities of parathyroid gland Acquired abnormalities of parathyroid gland Polyclonal cell proliferation (diffuse hyperplasia) – summative effect of each cell having a nonsuppressible basal secretion of PTH Polyclonal cell proliferation (diffuse hyperplasia) – summative effect of each cell having a nonsuppressible basal secretion of PTH Monoclonal cell proliferation – can lead to adenomatous cells that do not respond to appropriate feedback Monoclonal cell proliferation – can lead to adenomatous cells that do not respond to appropriate feedback

General indications for parathyroidectomy Symptomatic patients with elevated and nonsuppressible iPTH (usually >800) Symptomatic patients with elevated and nonsuppressible iPTH (usually >800) Hyperparathyroid bone disease – diagnosed by radiographical evidence or bone biopsy Hyperparathyroid bone disease – diagnosed by radiographical evidence or bone biopsy Extensive extraskeletal calcifications or calciphylaxis Extensive extraskeletal calcifications or calciphylaxis Refractory pruritis Refractory pruritis Unexplained myopathy Unexplained myopathy Severe hypercalcemia (mainly seen in primary HPTH) Severe hypercalcemia (mainly seen in primary HPTH)

Effects of parathyroidectomy

Effects cont. Parathyroidectomy may have beneficial effects on humoral immunity Parathyroidectomy may have beneficial effects on humoral immunity Prospective study 1999: 34 dialysis patients received parathyroidectomy for 2°HPTH. Prospective study 1999: 34 dialysis patients received parathyroidectomy for 2°HPTH. At 12 months there were significant increases in serum levels of IgG, IgM, IgA, C3, C4, and CH50 At 12 months there were significant increases in serum levels of IgG, IgM, IgA, C3, C4, and CH50 Nutrional status also improved as measured by significant increases in albumin and hematocrit Nutrional status also improved as measured by significant increases in albumin and hematocrit Am J Surg 1999 Oct;178(4):332-6.

VA Study 2004 – U. of Washington Observational matched cohort study of 4558 dialysis patients undergoing parathyroidectomy vs matched controls Observational matched cohort study of 4558 dialysis patients undergoing parathyroidectomy vs matched controls Higher 30 day mortality in parathyroidectomy group 3.1% vs. 1.2% in controls Higher 30 day mortality in parathyroidectomy group 3.1% vs. 1.2% in controls Long term survival better in parathyroidectomy group – 53 vs. 47 months Long term survival better in parathyroidectomy group – 53 vs. 47 months Survival curves crossed at 587 days s/p surgery Survival curves crossed at 587 days s/p surgery Kidney Int 2004 Nov;66(5):2010-6

Parathyroidectomy and transplant What to do with a patient with refractory hyperparathyroidism on transplant list? What to do with a patient with refractory hyperparathyroidism on transplant list? Most cases (approximately 96%) of HPT resolve after transplant Most cases (approximately 96%) of HPT resolve after transplant HPT that does not resolve may cause increased risk to the renal graft and may cause hypertension HPT that does not resolve may cause increased risk to the renal graft and may cause hypertension However, parathyroidectomy in transplant patients carries a small risk of sudden deterioration of renal graft function However, parathyroidectomy in transplant patients carries a small risk of sudden deterioration of renal graft function

Surgical considerations In primary HPTH, nuclear medicine scans (technetium-99m-sestamibi or I-123 SPECT) are used to detect location of glands prior to surgery In primary HPTH, nuclear medicine scans (technetium-99m-sestamibi or I-123 SPECT) are used to detect location of glands prior to surgery Unknown if useful in 2°HPT due to renal failure Unknown if useful in 2°HPT due to renal failure Total parathyroidectomy with autotransplantation is the most common technique Total parathyroidectomy with autotransplantation is the most common technique Reoperation rates for persistent HPT are 6-14% Reoperation rates for persistent HPT are 6-14%

Hungry bone syndrome Severe hypocalcemia following parathyroidectomy in spite of normal or elevated PTH levels Severe hypocalcemia following parathyroidectomy in spite of normal or elevated PTH levels Sudden decrease in PTH disrupts bone equilibrium of resorption vs. formation Sudden decrease in PTH disrupts bone equilibrium of resorption vs. formation Most common in patients with severe preexisting bone disease Most common in patients with severe preexisting bone disease Occurred in 20% of 148 dialysis patients undergoing parathyroidectomy in one series Occurred in 20% of 148 dialysis patients undergoing parathyroidectomy in one series Kidney Int Suppl 2003 Jun;(85):S97-100

Hungry bone syndrome cont. Hypocalcemia Hypocalcemia Nadirs 2-4 days post op Nadirs 2-4 days post op If tetany and seizures occur, they can increase fracture risk If tetany and seizures occur, they can increase fracture risk Sudden heart failure has been attributed to hypocalcemia Sudden heart failure has been attributed to hypocalcemia Hypophosphatemia and hypomagnesemia Hypophosphatemia and hypomagnesemia Mainly seen in primary HPTH Mainly seen in primary HPTH Hyperkalemia Hyperkalemia Occurs in 80% of dialysis patients post-op Occurs in 80% of dialysis patients post-op

Treatment Oral calcium – 2 to 4 g per day Oral calcium – 2 to 4 g per day IV calcium for symptomatic hypocalcemia or Ca < 7.5 – 1 amp of calcium gluconate instilled over 10 to 20 minutes followed by maintenance drip IV calcium for symptomatic hypocalcemia or Ca < 7.5 – 1 amp of calcium gluconate instilled over 10 to 20 minutes followed by maintenance drip Vitamin D supplementation – calcitriol Vitamin D supplementation – calcitriol Hemodialysis – use high calcium bath (3.5 mEq/L Ca) Hemodialysis – use high calcium bath (3.5 mEq/L Ca) Peritoneal dialysis – add 1 to 3 amps of calcium gluconate to each bag of dialysate Peritoneal dialysis – add 1 to 3 amps of calcium gluconate to each bag of dialysate