endocrine and metabolic disorders
Hyperparathyroidism
Treatment of Hyperparathyroidism
Sometimes medical management of hypercalcemia Often surgical parathyroidectomy Treatment for hyperparathyroidism depends on severity. Conservative management with methods to ensure that serum calcium concentrations remain low may be used for patients with who are either asymptomatic primary hyperparathyroidism with no indications for surgery. It may also be used for patients at high risk for surgery due to unrelated medical problems, but this is usually limited to patients with a shorter life expectancy because maintaining low serum calcium levels long-term may result in bone disease. Patients should do the following: Remain active (ie, avoid immobilization that could exacerbate hypercalcemia) Follow a low-calcium diet Drink plenty of fluids to minimize the chance of nephrolithiasis Avoid drugs that can raise serum calcium (eg, thiazide diuretics) Serum calcium and renal function are monitored every 6 months. Bone density is monitored every 12 months. However, recurrent hypercalcemia, subclinical bone disease, and hypertension are concerns. Patients with hypercalcemia alone can be managed withcinacalcet. Osteoporosis is treated with bisphosphonates. In patients with symptomatic or progressive hyperparathyroidism, surgery is indicated. The indications for surgery in patients with asymptomatic, primary hyperparathyroidism are controversial. Surgical parathyroidectomy increases bone density and may have modest effects on symptoms that impact quality of life, but most patients do not have progressive deterioration in biochemical abnormalities or bone density. Many experts recommend surgery in the following circumstances ( Treatment reference ): Serum calcium 1 mg/dL (0.25 mmol/L) greater than the upper limits of normal Hypercalciuria (> 250 mg/day [> 6.25 mmol/day] in women or > 300 mg/day [>7.5 mmol/day] in men) or the presence of nephrolithiasis Creatinine clearance < 60 mL/minute (<1 mL/second) Vertebral bone fracture or bone density at the hip, lumbar spine, or radius that is 2.5 standard deviations below controls (T score = −2.5) Age < 50 years The possibility of poor adherence with follow-up Surgery consists of removal of adenomatous gland(s).Parathyroid hormoneconcentration can be measured before and after removal of the presumed abnormal gland using rapid assays. A fall of ≥ 50% 10 minutes after removal of the adenoma indicates successful treatment. In patients with disease of > 1 gland, several glands are removed, and often a small portion of a normal-appearing parathyroid gland is reimplanted in a more accessible location in the body such as the belly of the sternocleidomastoid muscle or subcutaneously in the forearm to prevent hypoparathyroidism. Rarely, this residual gland is the source of recurrent secondary hyperparathyroidism, which can be managed with additional surgical removal. Parathyroid tissue is also occasionally preserved using cryopreservation to allow for later autologous transplantation in case persistent hypoparathyroidism develops. Serum calcium must be monitored several times a day in the immediate postoperative period. When surgery is done for mild hyperparathyroidism, the serum calcium concentration drops to just below normal within 24 to 48 hours. In patients with more severe or prolonged hyperparathyroidism, particularly secondary hyperparathyroidism with severe osteitis fibrosa cystica, prolonged, symptomatic hypocalcemia may occur postoperatively. When symptomatic hypocalcemia is expected, loading with 10 to 20 g elemental calcium in the days before surgery may prevent a precipitous postoperative decline in calcium. Even with preoperative calcium administration, large doses of calcium andvitamin Dmay be required in the postoperative period while bone calcium is repleted. Serum calcium must be monitored several times a day in the immediate postoperative period following parathyroidectomy In patients with severe hypercalcemia with primary hyperparathyroidism who are unable to undergo parathyroidectomy, medical treatment is indicated.Cinacalcet, a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to extracellular calcium, may lowerparathyroid hormoneand calcium levels. Although primary hyperparathyroidism can occur, hyperparathyroidism in patients with renal failure is usually secondary. Secondary hyperparathyroidism in patients with renal failure can result in a number of symptoms, including Osteitis fibrosa cystica with arthritis, bone pain, and pathologic fractures Spontaneous tendon rupture Proximal muscle weakness Extraskeletal calcifications, including soft tissue and vascular calcification Pruritis Secondary hyperparathyroidism can develop in patients with moderate chronic kidney disease (estimated glomerular filtration rate < 60 mL/minute), but it is usually more advanced in patients who require long-term dialysis. The interplay between phosphate retention, hypocalcemia, decreased activevitamin Dconcentration, and increased fibroblast growth factor-23 stimulates parathyroid secretion in patients with renal failure. Hyperphosphatemia None Vitamin Dadministration is potentially hazardous in patients with chronic kidney disease because it can increase phosphate as well as calcium concentrations and lead to accelerated vascular calcification;vitamin Dadministration requires frequent monitoring of calcium and phosphate levels. Treatment is generally limited to patients with renal failure patients and secondary hyperparathyroidism. Although oralcalcitriolis often given along with oral calcium to suppress secondary hyperparathyroidism, the results are variable in patients with end-stage renal disease. The parenteral form ofcalcitriol, orvitamin Danalogs such asparicalcitol, may better prevent secondary hyperparathyroidism in such patients, because the higher attained serum concentration of 1,25(OH)2D directly suppresses PTH release. The oral calcimimetic,cinacalcet, modulates the set point of the calcium-sensing receptor on parathyroid cells and decreases PTH concentration in dialysis patients without increasing serum calcium. Symptomatic hypocalcemia can develop withcinacalcet. It should not be started in patients with hypocalcemia at baseline, and calcium should be monitored frequently when titratingcinacalcetdose. Adherence can be limited by gastrointestinal intolerance. Another calcimimetic,etelcalcetide, is a parenteral alternative. Simple osteomalacia may respond tocalcitriol0.25 to 0.5 mcg orally once a day. In patients with osteomalacia caused by having taken large amounts of aluminum-containing phosphate binders, removal of aluminum withdeferoxamineis necessary beforecalcitrioladministration can reduce bone lesions. Progressive, severe elevation ofparathyroid hormonelevel that cannot be lowered by medical means without causing significant hyperphosphatemia or hypercalcemia requires surgery to prevent or reverse symptoms. A subtotal parathyroidectomy is done with reimplantation of a portion of the most normal appearing gland in the belly of the sternocleidomastoid muscle or subcutaneously in the forearm. Postoperatively, calcium can fall precipitously in patients with severe or long standing osteitis fibrosa cystica and is managed with oral and parenteral calcium and cholecalciferol. If the reimplanted parathyroid tissue does not produceparathyroid hormoneand the PTH level remains very low or undetectable, the patient will be at risk of developing osteomalacia as well as symptomatic hypocalcemia. Prolonged administration of as much as 2 mcg ofcalcitriolgiven orally once a day and ≥ 2 g of elemental calcium supplement per day is generally needed to support the calcium level. If after subtotal parathyroidectomy, patients with end-stage renal disease remain symptomatic due to hypocalcemia, adjustment can be made to the dialysate concentration of calcium. Tertiary hyperparathyroidism occurs when long-term stimulatory effects causing secondary hyperparathyroidism result in adenomatous transformation of parathyroid tissue. Patients with hypercalcemia as well as severe elevation of PTH while not taking cholecalciferol or calcium-containing phosphate binders suggests the presence of tertiary hyperparathyroidism. Adenomatous cells do not respond to medical treatment and require surgical intervention. 1.Bilezikian JP, Khan AA, Silverberg SJ, et al: Evaluation and management of primary hyperparathyroidism: Summary statement and guidelines from the Fifth International Workshop.J Bone Miner ResAug. 19, 2022. doi: 10.1002/jbmr.4677 