Management

Management

Renal transplantation remains the only definite treatment for secondary hyperparathyroidism. Other therapies are a bridge to this or aim to provide symptom relief. Standard manage - ment includes replacement of calcium and vitamin D and the reduction of phosphate levels by the use of phosphate binders. Treatment of this disease changed radically with the introduc - tion of calcimimetic drugs, such as cinacalcet. Calcimimetics alter the set point of the calcium-sensing receptor, thereby reducing the constant stimulation of the parathyroid glands and lowering the PTH lev el. This obviously does not address the underlying renal disease. It remains controversial as to which patients may benefit from the use of calcimimetics and which patients may benefit from earlier surgical intervention. Indications for pursuing medical management include those patients who are deemed non-surgical candidates by reason of medical comorbidities. Similarly , where there is persistent or recurrent disease, the origin of which cannot be clearly elucidated, surgical management should be avoided. However, there are definite indications for surgical intervention in secondary hyperparathyroidism ( Table 56.3 ), although these have been modified to reflect the current use, where available, of calcimimetics ( Table 56.4 ). There are a wide variety of operations that can be uti - lised for the management of secondary hyperparathyroidism, none of which appears significantly superior in terms of clin - ical outcomes (persistent or recurrent disease). These include a subtotal parathyroidectomy , a total para thyroidectomy with autograft or a total parathyroidectomy without autograft. Cryopr eservation of resected tissue, where available, should be - /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF

TABLE 56.3 Indications for surgical intervention in secondary hyperparathyroidism. Essential components 1. Persistently high serum level of intact PTH >500 /uni00A0 pg/mL 2. Hyperphosphataemia (serum PO

6 /uni00A0 mg/dL) or hypercalcaemia 4 (serum Ca >2.5 /uni00A0 mmol/L or 10 /uni00A0 mg/dL) which is refractory to medical management 3

Estimated volume of the largest gland >300–500 /uni00A0 mm or long axis >1 /uni00A0 cm Clinical /f_i ndings If patients have one of these symptoms, parathyroidectomy should be recommended: Severe osteitis /f_i brosa with associated high bone turnover Subjective symptoms (bone and joint pain, arthralgia, muscle weakness, irritability, pruritus, depression) Progressive ectopic calci /f_i cation Calciphylaxis Progressive reduction in bone mineral content Anaemia resistant to ESA Dilated cardiomyopathy/cardiac failure ESA, erythropoietin-stimulating agent; PTH, parathyroid hormone.

/uni25CF /uni25CF /uni25CF /uni25CF performed in cases of significant postoperative hypocalcaemia. The first two procedures are most widely accepted and the type of operation performed depends upon the surgeon. A subtotal parathyroidectomy is where three and a half parathyroid glands are excised, with the remnant being marked with a non-absorbable stitch to facilitate identification in the event of recur rent disease. A biopsy of the final gland that is to be left in situ is mandatory to confirm the presence of residual parathyroid tissue. Ideally an inferior gland is left in situ to facil itate reoperative surgery and minimise potential damage to the recurrent laryngeal nerve in that setting ( Figure 56.10 ). A total parathyroidectomy with a forearm autograft in volves removal of all parathyroid tissue in the neck, with reimplantation of a small amount of morcellated tissue within a pocket formed in the brachioradialis muscle. Overall, regardless of the operative approach utilised the cure rate ranges between 90% and 96%, with similar complication rates. A randomised study looking at 40 patients who underwent either a subtotal or total parathy roidectomy with autotransplant demonstrated no significant di ff erence between the two operations in terms of e ffi cacy and recurrence rate (Rothm und et al ., 1991). The response to surgical intervention is often dramatic. The biochemical parameters may resolve almost immediately and appear to be sustained for up to 3 years postoperatively . Patients subjectively report improvements in the symptoms of secondary hyperparathyroidism, including bone pain, pruritus, fatigue and depression. Finally , bone metabolism is improved with an approximate 10% increase in trabecular bone, with almost immediate suppression of bone resorption and acceleration of new bone formation. Secondary hyperparathyroidism /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF

management of secondary hyperparathyroidism (SHPT) in the era of calcimimetics. When SHPT is refractory to vitamin D replacement or vitamin D analogues and prolonged survival is anticipated Severely impaired quality of life owing to either SHPT or intolerance to calcimimetics When suf /f_i cient reduction in parathyroid hormone cannot be achieved with use of calcimimetics Thyroid surgery is also required (thyroid carcinoma) Figure 56.10 Subtotal parathyroidectomy for parathyroid hyperplasia. Right inferior gland biopsied and half left in situ . Primarily due to underlying chronic kidney disease Associated with parathyroid hyperplasia Diagnosis is made biochemically with a low or normal calcium and an elevated PTH. High phosphate levels and low vitamin D levels are seen No localisation studies are required Mainstay of treatment is renal transplantation. Medical management with calcium and vitamin D replacements and phosphate binders is a bridge to transplantation Use of calcimimetics has reduced the requirement for surgical intervention Subtotal parathyroidectomy remains the surgical intervention of choice when indicated

Management

Renal transplantation remains the only definite treatment for secondary hyperparathyroidism. Other therapies are a bridge to this or aim to provide symptom relief. Standard manage - ment includes replacement of calcium and vitamin D and the reduction of phosphate levels by the use of phosphate binders. Treatment of this disease changed radically with the introduc - tion of calcimimetic drugs, such as cinacalcet. Calcimimetics alter the set point of the calcium-sensing receptor, thereby reducing the constant stimulation of the parathyroid glands and lowering the PTH lev el. This obviously does not address the underlying renal disease. It remains controversial as to which patients may benefit from the use of calcimimetics and which patients may benefit from earlier surgical intervention. Indications for pursuing medical management include those patients who are deemed non-surgical candidates by reason of medical comorbidities. Similarly , where there is persistent or recurrent disease, the origin of which cannot be clearly elucidated, surgical management should be avoided. However, there are definite indications for surgical intervention in secondary hyperparathyroidism ( Table 56.3 ), although these have been modified to reflect the current use, where available, of calcimimetics ( Table 56.4 ). There are a wide variety of operations that can be uti - lised for the management of secondary hyperparathyroidism, none of which appears significantly superior in terms of clin - ical outcomes (persistent or recurrent disease). These include a subtotal parathyroidectomy , a total para thyroidectomy with autograft or a total parathyroidectomy without autograft. Cryopr eservation of resected tissue, where available, should be - /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF

TABLE 56.3 Indications for surgical intervention in secondary hyperparathyroidism. Essential components 1. Persistently high serum level of intact PTH >500 /uni00A0 pg/mL 2. Hyperphosphataemia (serum PO

6 /uni00A0 mg/dL) or hypercalcaemia 4 (serum Ca >2.5 /uni00A0 mmol/L or 10 /uni00A0 mg/dL) which is refractory to medical management 3

Estimated volume of the largest gland >300–500 /uni00A0 mm or long axis >1 /uni00A0 cm Clinical /f_i ndings If patients have one of these symptoms, parathyroidectomy should be recommended: Severe osteitis /f_i brosa with associated high bone turnover Subjective symptoms (bone and joint pain, arthralgia, muscle weakness, irritability, pruritus, depression) Progressive ectopic calci /f_i cation Calciphylaxis Progressive reduction in bone mineral content Anaemia resistant to ESA Dilated cardiomyopathy/cardiac failure ESA, erythropoietin-stimulating agent; PTH, parathyroid hormone.

/uni25CF /uni25CF /uni25CF /uni25CF performed in cases of significant postoperative hypocalcaemia. The first two procedures are most widely accepted and the type of operation performed depends upon the surgeon. A subtotal parathyroidectomy is where three and a half parathyroid glands are excised, with the remnant being marked with a non-absorbable stitch to facilitate identification in the event of recur rent disease. A biopsy of the final gland that is to be left in situ is mandatory to confirm the presence of residual parathyroid tissue. Ideally an inferior gland is left in situ to facil itate reoperative surgery and minimise potential damage to the recurrent laryngeal nerve in that setting ( Figure 56.10 ). A total parathyroidectomy with a forearm autograft in volves removal of all parathyroid tissue in the neck, with reimplantation of a small amount of morcellated tissue within a pocket formed in the brachioradialis muscle. Overall, regardless of the operative approach utilised the cure rate ranges between 90% and 96%, with similar complication rates. A randomised study looking at 40 patients who underwent either a subtotal or total parathy roidectomy with autotransplant demonstrated no significant di ff erence between the two operations in terms of e ffi cacy and recurrence rate (Rothm und et al ., 1991). The response to surgical intervention is often dramatic. The biochemical parameters may resolve almost immediately and appear to be sustained for up to 3 years postoperatively . Patients subjectively report improvements in the symptoms of secondary hyperparathyroidism, including bone pain, pruritus, fatigue and depression. Finally , bone metabolism is improved with an approximate 10% increase in trabecular bone, with almost immediate suppression of bone resorption and acceleration of new bone formation. Secondary hyperparathyroidism /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF

management of secondary hyperparathyroidism (SHPT) in the era of calcimimetics. When SHPT is refractory to vitamin D replacement or vitamin D analogues and prolonged survival is anticipated Severely impaired quality of life owing to either SHPT or intolerance to calcimimetics When suf /f_i cient reduction in parathyroid hormone cannot be achieved with use of calcimimetics Thyroid surgery is also required (thyroid carcinoma) Figure 56.10 Subtotal parathyroidectomy for parathyroid hyperplasia. Right inferior gland biopsied and half left in situ . Primarily due to underlying chronic kidney disease Associated with parathyroid hyperplasia Diagnosis is made biochemically with a low or normal calcium and an elevated PTH. High phosphate levels and low vitamin D levels are seen No localisation studies are required Mainstay of treatment is renal transplantation. Medical management with calcium and vitamin D replacements and phosphate binders is a bridge to transplantation Use of calcimimetics has reduced the requirement for surgical intervention Subtotal parathyroidectomy remains the surgical intervention of choice when indicated