Nephrology Nephrology Grand RoundsGrand Rounds

5/13/085/13/08

Refractory Refractory HyperparathyroidHyperparathyroid

ismismBrad WeaverBrad Weaver

Causes of refractory Causes of refractory HPTHHPTH

Inadequate therapyInadequate therapy Persistent hyperphosphatemiaPersistent hyperphosphatemia Acquired abnormalities of parathyroid Acquired abnormalities of parathyroid

glandgland Polyclonal cell proliferation (diffuse Polyclonal cell proliferation (diffuse

hyperplasia) – summative effect of each cell hyperplasia) – summative effect of each cell having a nonsuppressible basal secretion of having a nonsuppressible basal secretion of PTHPTH

Monoclonal cell proliferation – can lead to Monoclonal cell proliferation – can lead to adenomatous cells that do not respond to adenomatous cells that do not respond to appropriate feedbackappropriate feedback

General indications for General indications for parathyroidectomyparathyroidectomy

Symptomatic patients with elevated and Symptomatic patients with elevated and nonsuppressible iPTH (usually >800)nonsuppressible iPTH (usually >800)

Hyperparathyroid bone disease – diagnosed Hyperparathyroid bone disease – diagnosed by radiographical evidence or bone biopsyby radiographical evidence or bone biopsy

Extensive extraskeletal calcifications or Extensive extraskeletal calcifications or calciphylaxiscalciphylaxis

Refractory pruritisRefractory pruritis Unexplained myopathyUnexplained myopathy Severe hypercalcemia (mainly seen in Severe hypercalcemia (mainly seen in

primary HPTH)primary HPTH)

Effects of Effects of parathyroidectomyparathyroidectomy

Effects cont.Effects cont.

Parathyroidectomy may have beneficial Parathyroidectomy may have beneficial effects on humoral immunityeffects on humoral immunity

Prospective study 1999: 34 dialysis Prospective study 1999: 34 dialysis patients received parathyroidectomy for patients received parathyroidectomy for 22°HPTH. °HPTH. At 12 months there were significant increases At 12 months there were significant increases

in serum levels of IgG, IgM, IgA, C3, C4, and in serum levels of IgG, IgM, IgA, C3, C4, and CH50CH50

Nutrional status also improved as measured by Nutrional status also improved as measured by significant increases in albumin and significant increases in albumin and hematocrithematocrit

Am J Surg 1999 Oct;178(4):332-6.

VA Study 2004 – U. of VA Study 2004 – U. of WashingtonWashington

Observational matched cohort study of 4558 Observational matched cohort study of 4558 dialysis patients undergoing dialysis patients undergoing parathyroidectomy vs. 4558 matched controlsparathyroidectomy vs. 4558 matched controls

Higher 30 day mortality in parathyroidectomy Higher 30 day mortality in parathyroidectomy group 3.1% vs. 1.2% in controlsgroup 3.1% vs. 1.2% in controls

Long term survival better in Long term survival better in parathyroidectomy group – 53 vs. 47 monthsparathyroidectomy group – 53 vs. 47 months

Survival curves crossed at 587 days s/p Survival curves crossed at 587 days s/p surgerysurgery

Kidney Int 2004 Nov;66(5):2010-6

Parathyroidectomy and Parathyroidectomy and transplanttransplant

What to do with a patient with refractory What to do with a patient with refractory hyperparathyroidism on transplant list?hyperparathyroidism on transplant list? Most cases (approximately 96%) of HPT Most cases (approximately 96%) of HPT

resolve after transplantresolve after transplant HPT that does not resolve may cause HPT that does not resolve may cause

increased risk to the renal graft and may increased risk to the renal graft and may cause hypertensioncause hypertension

However, parathyroidectomy in transplant However, parathyroidectomy in transplant patients carries a small risk of sudden patients carries a small risk of sudden deterioration of renal graft functiondeterioration of renal graft function

Surgical considerationsSurgical considerations

In primary HPTH, nuclear medicine scans In primary HPTH, nuclear medicine scans (technetium-99m-sestamibi or I-123 (technetium-99m-sestamibi or I-123 SPECT) are used to detect location of SPECT) are used to detect location of glands prior to surgeryglands prior to surgery Unknown if useful in 2Unknown if useful in 2°HPT due to renal failure°HPT due to renal failure

Total parathyroidectomy with Total parathyroidectomy with autotransplantation is the most common autotransplantation is the most common techniquetechnique

Reoperation rates for persistent HPT are 6-Reoperation rates for persistent HPT are 6-14%14%

Hungry bone syndromeHungry bone syndrome

Severe hypocalcemia following Severe hypocalcemia following parathyroidectomy in spite of normal parathyroidectomy in spite of normal or elevated PTH levelsor elevated PTH levels

Sudden decrease in PTH disrupts bone Sudden decrease in PTH disrupts bone equilibrium of resorption vs. formationequilibrium of resorption vs. formation

Most common in patients with severe Most common in patients with severe preexisting bone diseasepreexisting bone disease

Occurred in 20% of 148 dialysis Occurred in 20% of 148 dialysis patients undergoing patients undergoing parathyroidectomy in one seriesparathyroidectomy in one series

Kidney Int Suppl 2003 Jun;(85):S97-100

Hungry bone syndrome Hungry bone syndrome cont.cont.

HypocalcemiaHypocalcemia Nadirs 2-4 days post opNadirs 2-4 days post op If tetany and seizures occur, they can If tetany and seizures occur, they can

increase fracture riskincrease fracture risk Sudden heart failure has been attributed to Sudden heart failure has been attributed to

hypocalcemiahypocalcemia Hypophosphatemia and hypomagnesemiaHypophosphatemia and hypomagnesemia

Mainly seen in primary HPTHMainly seen in primary HPTH Hyperkalemia Hyperkalemia

Occurs in 80% of dialysis patients post-opOccurs in 80% of dialysis patients post-op

TreatmentTreatment

Oral calcium – 2 to 4 g per dayOral calcium – 2 to 4 g per day IV calcium for symptomatic hypocalcemia or IV calcium for symptomatic hypocalcemia or

Ca < 7.5 – 1 amp of calcium gluconate Ca < 7.5 – 1 amp of calcium gluconate instilled over 10 to 20 minutes followed by instilled over 10 to 20 minutes followed by maintenance dripmaintenance drip

Vitamin D supplementation – calcitriolVitamin D supplementation – calcitriol Hemodialysis – use high calcium bath (3.5 Hemodialysis – use high calcium bath (3.5

mEq/L Ca)mEq/L Ca) Peritoneal dialysis – add 1 to 3 amps of Peritoneal dialysis – add 1 to 3 amps of

calcium gluconate to each bag of dialysatecalcium gluconate to each bag of dialysate