What are the current treatment options for a young male patient with Multiple Endocrine Neoplasia (MEN) syndrome, who has undergone two surgeries for parathyroid adenoma removal in 2019 and 2022, and still experiences persistent Hypercalcemia, but is intolerant to Cinacalcet (Cinacalcet hydrochloride)?

From the Guidelines

For a young patient with MEN1 syndrome who has persistent hypercalcemia after two parathyroid surgeries and is intolerant to cinacalcet, I strongly recommend considering intravenous bisphosphonates as the primary treatment option, as this approach has been shown to effectively reduce serum calcium levels in patients with primary hyperparathyroidism 1. Given the patient's history of multiple surgeries and intolerance to cinacalcet, it is crucial to prioritize treatments that can manage hypercalcemia while minimizing the risk of further complications.

• The patient's condition is complex, with a history of two parathyroid surgeries, and the presence of MEN1 syndrome, which increases the risk of developing multiple endocrine neoplasias 1.
• The use of intravenous bisphosphonates, such as zoledronic acid (4 mg IV every 3-6 months) or pamidronate (60-90 mg IV every 3-4 months), can effectively reduce serum calcium levels by inhibiting bone resorption 1.
• Denosumab (60-120 mg subcutaneously every 6 months) is an alternative option if bisphosphonates are contraindicated or ineffective, as it can also reduce serum calcium levels by inhibiting bone resorption 1.
• In addition to medical management, the patient should maintain adequate hydration, follow a low-calcium diet (limiting intake to 800-1000 mg daily), and avoid thiazide diuretics, which can worsen hypercalcemia 1.
• Regular monitoring of serum calcium, phosphorus, vitamin D, and renal function is essential to ensure the effectiveness of the treatment and prevent potential complications 1.
• For long-term management, consideration should be given to referral to a specialized endocrine surgeon experienced in MEN1 for evaluation of possible remaining parathyroid tissue or ectopic glands that might have been missed in previous surgeries, as the persistent hypercalcemia suggests either incomplete removal of abnormal parathyroid tissue or the development of new adenomas 1.

From the FDA Drug Label

2.4 Switching from Cinacalcet to PARSABIV Discontinue cinacalcet for at least 7 days prior to starting PARSABIV, and initiate PARSABIV treatment at a starting dose of 5 mg. Ensure corrected serum calcium is at or above the lower limit of normal prior to PARSABIV initiation

The patient's current treatment options include:

• Etelcalcetide (PARSABIV): The patient can be switched to etelcalcetide, with a starting dose of 5 mg, after discontinuing cinacalcet for at least 7 days.
• Zoledronic acid: This medication can be used to treat hypercalcemia, but its use in this specific case would depend on the patient's overall clinical condition and the presence of any contraindications. It is essential to closely monitor the patient's corrected serum calcium and parathyroid hormone (PTH) levels during the treatment with etelcalcetide or zoledronic acid, as well as to adjust the dose accordingly to avoid hypocalcemia and other potential side effects 2, 3.

From the Research

Current Treatment Options

The patient has undergone two surgeries for parathyroid adenoma removal in 2019 and 2022, but still experiences persistent hypercalcemia and is intolerant to cinacalcet. Considering the patient's condition, the following treatment options are available:

• Hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate, as initial therapy for symptomatic or severe hypercalcemia 4
• Denosumab, which has been shown to be effective in treating hypercalcemia in patients with primary hyperparathyroidism (PHPT) and parathyroid carcinoma 5, 6, 7
• Calcitonin, which is preferable for short-term control of severe hypercalcemia 5
• Glucocorticoids, which may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption 4

Considerations for Treatment

When selecting a treatment option, the following factors should be considered:

• The patient's underlying cause of hypercalcemia, which in this case is primary hyperparathyroidism
• The patient's intolerance to cinacalcet, which may influence the choice of treatment
• The potential side effects and risks associated with each treatment option, such as hypocalcemia with denosumab 7
• The need for ongoing monitoring and adjustment of treatment to manage the patient's hypercalcemia effectively

Treatment Efficacy

Studies have shown that denosumab is effective in reducing serum calcium levels in patients with PHPT-related hypercalcemia, with a response rate of 82.8% and a complete response rate of 72.4% 7. Zoledronic acid has also been shown to be effective in reducing serum calcium levels, with a similar response rate to denosumab 7. The choice of treatment will depend on the patient's individual needs and circumstances.