What is the workup for tertiary hyperparathyroidism (Hyperparathyroidism)

From the Guidelines

Tertiary hyperparathyroidism workup should begin with laboratory tests including serum calcium, phosphorus, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, and assessment of renal function with BUN and creatinine, as the initial step in diagnosis and management, according to the most recent guidelines 1.

Initial Evaluation

The workup for tertiary hyperparathyroidism involves several key components:

• Laboratory tests: serum calcium, phosphorus, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D
• Assessment of renal function: BUN and creatinine
• Imaging studies: neck ultrasound to evaluate parathyroid gland size and number, followed by a sestamibi scan with SPECT/CT to localize hyperfunctioning glands
• Bone density testing (DEXA scan) to assess for bone disease

Management

Treatment typically involves:

• Surgical parathyroidectomy when calcium levels remain persistently elevated (>10.2 mg/dL) with inappropriately high PTH levels despite normal or improved renal function 1
• Medical management with calcimimetics like cinacalcet (starting at 30 mg daily, titrating up to 180 mg daily as needed) may be used in patients who are poor surgical candidates
• Monitoring of calcium and PTH levels every 3 months for the first year post-transplant, then annually if stable in patients with kidney transplants

Considerations

Tertiary hyperparathyroidism develops from long-standing secondary hyperparathyroidism, typically in patients with chronic kidney disease, where parathyroid glands become autonomously functioning and continue to secrete excessive PTH despite correction of the initial stimulus (such as after successful kidney transplantation), leading to hypercalcemia rather than the normocalcemia or hypocalcemia seen in secondary hyperparathyroidism 1. Key considerations include:

• The role of cinacalcet in managing secondary hyperparathyroidism and its potential use in tertiary hyperparathyroidism
• The importance of monitoring for complications such as nephrocalcinosis and hypercalcemia
• The need for a multidisciplinary approach to management, including surgery, medical therapy, and monitoring of calcium and PTH levels.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Secondary Hyperparathyroidism Cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis [see Clinical Studies (14. 1)]. 1.2 Parathyroid Carcinoma Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma [see Clinical Studies(14.2)].

1. 3 Primary Hyperparathyroidism Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy [see Clinical Studies (14.3)].

The FDA drug label does not answer the question.

From the Research

Tertiary Hyperparathyroidism Workup

• Tertiary hyperparathyroidism (HPT III) is a condition where an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism 2.
• The condition can occur after successful renal transplantation, where the hypertrophied parathyroid tissue fails to resolve and continues to oversecrete PTH despite normal or elevated serum calcium levels 2.
• Tertiary HPT can also be caused by long-term oral phosphate therapy, as seen in a case report of a 35-year-old woman with familial hypophosphatemic rickets 3.

Diagnostic Considerations

• Laboratory studies may show findings consistent with secondary HPT, such as elevated intact parathyroid hormone, calcium, and phosphorus levels 3.
• Imaging studies, such as ultrasonography, technetium Tc 99m sestamibi, and magnetic resonance imaging, may not identify ectopic or supernumerary glands 4.
• Histologic patterns of disease may show parathyroid hyperplasia, and bilateral neck exploration with subtotal or total parathyroidectomy with autotransplantation may be necessary to obtain long-term cure 4.

Treatment Options

• Surgical parathyroidectomy is a primary treatment option for tertiary HPT, with three commonly performed procedures: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy 2.
• Other treatment options include vitamin D supplements, phosphate binders, and calcimimetics 5.
• Determining the optimal treatment for the individual patient is challenging and requires careful consideration of the patient's specific condition and medical history 5.