What is secondary hyperparathyroidism (Secondary Hyperparathyroidism)?

From the Guidelines

Secondary hyperparathyroidism should be managed with a combination of dietary phosphate restriction, phosphate binders, active vitamin D analogs, and calcimimetics, with parathyroidectomy considered in severe cases, as recommended by the most recent guidelines 1.

Treatment Overview

The treatment of secondary hyperparathyroidism focuses on addressing the underlying cause and normalizing calcium, phosphate, and PTH levels. For CKD-related cases, management includes:

• Dietary phosphate restriction (800-1000 mg/day)
• Phosphate binders (such as calcium acetate, sevelamer, or lanthanum)
• Active vitamin D analogs (calcitriol 0.25-1 mcg daily, paricalcitol 1-2 mcg daily)
• Calcimimetics (cinacalcet starting at 30 mg daily, titrated up to 180 mg if needed) For vitamin D deficiency cases, supplementation with cholecalciferol (vitamin D3) 1000-2000 IU daily or ergocalciferol (vitamin D2) 50,000 IU weekly for 8-12 weeks is recommended, followed by maintenance therapy.

Monitoring and Adjustments

Regular monitoring of calcium, phosphate, PTH, and vitamin D levels is essential to adjust treatment. If medical management fails, especially in severe cases with bone disease or calcifications, parathyroidectomy may be necessary, as supported by recent studies 1.

Pathophysiology

The condition develops because low calcium or high phosphate levels stimulate PTH secretion, which normally helps maintain calcium homeostasis but becomes pathological when chronically elevated, leading to bone disease, vascular calcification, and increased cardiovascular risk, as described in previous guidelines 1.

Recent Recommendations

Recent studies and guidelines recommend considering parathyroidectomy in cases of severe secondary hyperparathyroidism, especially when medical management fails 1. The choice of surgical approach, including subtotal parathyroidectomy, total parathyroidectomy, and total parathyroidectomy with autotransplantation, depends on various factors, including the severity of the disease and the patient's overall health, as discussed in recent reviews 1.

From the FDA Drug Label

Cinacalcet reduced iPTH while lowering Ca x P, calcium, and phosphorus levels (Table 7, Figure 2). In the primary efficacy analysis, 40% of the patients on cinacalcet and 5% of placebo-treated patients achieved an iPTH ≤ 250 pg/mL (p < 0. 001)

Cinacalcet is effective in treating secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, as it reduces iPTH levels and achieves the primary endpoint of iPTH ≤ 250 pg/mL in a significant proportion of patients.

• The medication lowers Ca x P, calcium, and phosphorus levels, which is beneficial for patients with secondary hyperparathyroidism.
• 40% of patients on cinacalcet achieved an iPTH ≤ 250 pg/mL, compared to 5% of placebo-treated patients.
• The median dose of cinacalcet at the completion of the studies was 90 mg. 2

From the Research

Definition and Causes of Secondary Hyperparathyroidism

• Secondary hyperparathyroidism (SHPT) is a condition that arises as a result of chronic uremia, leading to a combination of phosphate retention, failure of calcitriol synthesis, and hypocalcemia 3.
• It is commonly developed in patients with chronic kidney disease (CKD) in response to high phosphate, low calcium, and low 1,25-dihydroxyvitamin D(3) levels 4.

Treatment and Management of Secondary Hyperparathyroidism

• Therapies used to correct these abnormalities include active vitamin D replacement, calcium supplementation, and phosphate restriction, but they have moderate efficacy and are prone to unacceptable side-effects 3.
• New developments in the control of phosphate, vitamin D replacement, and modulation of the calcium-sensing receptor (CaSR) using calcimimetics have been made 3.
• Vitamin D analogs, such as paricalcitol and doxercalciferol, have been developed to inhibit PTH gene transcription and parathyroid hyperplasia with less calcemic activity than 1,25-dihydroxyvitamin D(3) 4, 5.
• Cinacalcet, a calcimimetic agent, has been shown to reduce the concentrations of PTH, calcium, and phosphate in hemodialysis patients, enabling a significant number to achieve target ranges 3.

Vitamin D and Secondary Hyperparathyroidism

• The interplay between vitamin D and parathyroid hormone (PTH) represents one of the most important metabolic mechanisms of regulation of calcium/phosphorus homeostasis 6.
• Secondary hyperparathyroidism is a major complication that arises as a result of reduced vitamin D levels, both as primary 25-hydroxy-vitamin D and/or 1,25-dihydroxyvitamin D reduction 6.
• Therapeutic intervention is primarily aimed at enhancing serum 25(OH)D levels and reducing secondary hyperparathyroidism, by employing different strategies and endpoints according to the clinical context 6.

Clinical Complications and Consequences

• Secondary hyperparathyroidism can lead to clinical complications such as vascular calcification, coronary artery disease, and adynamic bone disease 4.
• The skeleton is primarily involved, but many other extra-skeletal organs expressing the vitamin D and/or PTH receptors may be affected by vitamin D inadequacy and secondary hyperparathyroidism 6.
• Chronic kidney disease (CKD) can be intensified by low vitamin D and high serum PTH, leading to further consequences on the mineral metabolism system and development of skeletal and cardiovascular disease 6.