What are the steps for diagnosing and managing primary hyperparathyroidism (PHPT)?

From the Guidelines

Diagnosing and managing primary hyperparathyroidism (PHPT) requires a systematic approach beginning with laboratory testing and ending with appropriate treatment selection, with the most recent and highest quality study 1 guiding the approach. The initial diagnosis involves measuring serum calcium and parathyroid hormone (PTH) levels, with elevated calcium and inappropriately normal or elevated PTH being diagnostic. Additional tests include 25-hydroxyvitamin D, serum phosphorus, 24-hour urinary calcium, and renal function tests. Imaging studies are not used for diagnosis but for localization before surgery, typically with ultrasound and sestamibi scanning, as stated in 1 and 1. Bone density testing (DXA scan) should be performed to assess skeletal involvement. Management depends on whether the patient is symptomatic or meets surgical criteria. **Surgery (parathyroidectomy) is the definitive treatment for symptomatic patients or those meeting criteria: age under 50, serum calcium >1 mg/dL above normal, osteoporosis (T-score ≤-2.5), kidney stones, or creatinine clearance <60 mL/min, as recommended in 1.** For asymptomatic patients not meeting surgical criteria, monitoring is appropriate with calcium and PTH measurements annually and bone density testing every 1-2 years. Medical management options include cinacalcet (30-90 mg daily) for those who cannot undergo surgery, along with adequate hydration, avoiding thiazide diuretics, and ensuring sufficient vitamin D levels (target >20 ng/mL) without excessive calcium supplementation, as suggested in 1. Bisphosphonates may be considered for patients with significant bone loss. Regular follow-up is essential to monitor disease progression and treatment efficacy. Key considerations in the management of PHPT include the role of imaging in preoperative localization, the selection of surgical approach, and the importance of long-term follow-up to monitor for potential recurrence or persistence of disease, as discussed in 1, 1, and 1.

From the FDA Drug Label

Sixty-seven patients with primary HPT who met criteria for parathyroidectomy on the basis of corrected total serum calcium (> 11.3 mg/dL [2.82 mmol/L] and ≤ 12.5 mg/dL [3. 12 mmol/L]), but who were unable to undergo parathyroidectomy participated in a randomized, double-blind, placebo-controlled study.

The steps for diagnosing and managing primary hyperparathyroidism (PHPT) are not explicitly outlined in the provided drug labels. However, the labels do mention a study involving 67 patients with primary HPT who met criteria for parathyroidectomy, indicating that corrected total serum calcium levels are used to determine the need for parathyroidectomy.

• The criteria for parathyroidectomy include a corrected total serum calcium level of > 11.3 mg/dL and ≤ 12.5 mg/dL.
• Management of PHPT may involve treatment with cinacalcet, which has been shown to reduce serum calcium levels in patients with primary HPT 2.
• Patients with severe hypercalcemia due to primary HPT may require a dose-titration phase and a maintenance phase of cinacalcet treatment 2.

From the Research

Diagnosis of Primary Hyperparathyroidism (PHPT)

• The diagnosis of PHPT is biochemical, with asymptomatic hypercalcemia being the most frequent manifestation of the disease 3.
• Measurement of parathyroid hormone (PTH) levels is essential for diagnosis, along with phosphate, chloride, 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, and calcium-to-creatinine clearance 3.
• The oral calcium-loading test with measurement of intact PTH can be a valuable adjunct in confirming the diagnosis of PHPT in patients with symptoms who have minimal, intermittent, or no elevation of total calcium and/or PTH levels 4.

Localization of Parathyroid Tumors

• After biochemical confirmation, further diagnostic tests aim to locate the tumor, using ultrasound and 99m TC-sestamibi scintigraphy 5.
• Localization of the hyperfunctioning parathyroid gland is crucial for surgical removal, and an experienced surgical team is essential to achieve curative parathyroidectomy 6.

Management of PHPT

• Surgical removal of the hyperfunctioning parathyroid gland is the standard management for symptomatic PHPT 5, 6.
• Medical management, including bisphosphonates and calcimimetics, can be a promising option for asymptomatic patients who are not candidates for parathyroidectomy 7, 5.
• Bisphosphonates and hormone replacement therapy can decrease bone turnover and improve bone mineral density in patients with PHPT, while calcimimetics can lower serum calcium and PTH levels 7.

Treatment Options

• Bisphosphonates are the first choice for medical treatment in patients with bone manifestation, and cinacalcet may be given to patients to lower calcium and PTH levels 5.
• Non-surgical treatment may be justified in asymptomatic and elderly patients, and medical management can provide skeletal protection in patients with PHPT 7, 5.