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Nephrology Grand Rounds. 5/13/08. Refractory Hyperparathyroidism. Brad Weaver. Causes of refractory HPTH. Inadequate therapy Persistent hyperphosphatemia Acquired abnormalities of parathyroid gland
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Nephrology Grand Rounds 5/13/08
Refractory Hyperparathyroidism Brad Weaver
Causes of refractory HPTH • Inadequate therapy • Persistent hyperphosphatemia • Acquired abnormalities of parathyroid gland • 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
General indications for parathyroidectomy • Symptomatic patients with elevated and nonsuppressible iPTH (usually >800) • Hyperparathyroid bone disease – diagnosed by radiographical evidence or bone biopsy • Extensive extraskeletal calcifications or calciphylaxis • Refractory pruritis • Unexplained myopathy • Severe hypercalcemia (mainly seen in primary HPTH)
Effects cont. • Parathyroidectomy may have beneficial effects on humoral immunity • 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 • 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. 4558 matched 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 • 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? • 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 • 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 • Unknown if useful in 2°HPT due to renal failure • Total parathyroidectomy with autotransplantation is the most common technique • Reoperation rates for persistent HPT are 6-14%
Hungry bone syndrome • Severe hypocalcemia following parathyroidectomy in spite of normal or elevated PTH levels • Sudden decrease in PTH disrupts bone equilibrium of resorption vs. formation • Most common in patients with severe preexisting bone disease • 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 • Nadirs 2-4 days post op • If tetany and seizures occur, they can increase fracture risk • Sudden heart failure has been attributed to hypocalcemia • Hypophosphatemia and hypomagnesemia • Mainly seen in primary HPTH • Hyperkalemia • Occurs in 80% of dialysis patients post-op
Treatment • 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 • Vitamin D supplementation – calcitriol • 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