How are inherited hypercalcemia disorders managed?

From the Guidelines

Inherited hypercalcemia disorders are best managed with a personalized approach, focusing on controlling calcium levels and treating underlying causes, with surgical excision of abnormal parathyroid tissue being the only definitive cure for primary hyperparathyroidism (PHPT) 1.

Management Strategies

The management of inherited hypercalcemia disorders involves a range of strategies, including:

• Controlling calcium levels through adequate hydration and loop diuretics like furosemide (20-40mg IV or oral) to increase urinary calcium excretion
• Using bisphosphonates such as zoledronic acid (4mg IV) or pamidronate (60-90mg IV) for acute hypercalcemia by inhibiting bone resorption
• Observation for familial hypocalciuric hypercalcemia (FHH) patients who typically remain asymptomatic
• Parathyroidectomy for symptomatic primary hyperparathyroidism patients or those with significant hypercalcemia (>1mg/dL above normal)
• Medical management with cinacalcet (30-90mg daily) for those who cannot undergo surgery by sensitizing calcium-sensing receptors

Surgical Approach

Surgical excision of abnormal parathyroid tissue is the only definitive cure for PHPT, with two accepted curative operative strategies: bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP) 1.

• BNE is a bilateral operation in which all parathyroid glands are identified and examined by the surgeon, who resects the diseased glands
• MIP is a unilateral operation utilizing limited dissection for targeted removal of only the affected gland, requiring confident and precise preoperative localization of a single parathyroid adenoma

Imaging and Localization

Imaging plays a crucial role in localizing the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery, with no utility in confirming or excluding the diagnosis of PHPT 1.

• Preoperative imaging is essential in the reoperative setting to localize a target parathyroid lesion (or lesions) and to identify postoperative changes from previous parathyroid explorations that can impact a subsequent surgery

Monitoring and Follow-up

Regular monitoring of serum calcium, phosphorus, PTH, and vitamin D levels is essential, along with renal function assessment, to individualize treatment based on the specific genetic disorder, severity of hypercalcemia, and presence of symptoms 1.

From the FDA Drug Label

1.1 Secondary Hyperparathyroidism 1.2 Parathyroid Carcinoma 1.3 Primary Hyperparathyroidism

The management of inherited hypercalcemia disorders is not directly addressed in the provided drug label for cinacalcet (PO) 2. However, the label does mention Primary Hyperparathyroidism as an indication, which can be a cause of hypercalcemia.

• Primary Hyperparathyroidism is managed with cinacalcet, as stated in the label. However, inherited hypercalcemia disorders are not explicitly mentioned, and therefore, no conclusion can be drawn about their management from this label.

From the Research

Inherited Hypercalcemia Disorders

Inherited hypercalcemia disorders, such as familial hypocalciuric hypercalcemia (FHH), are managed through a combination of diagnosis, counseling, and treatment options.

• The main challenge in managing FHH is distinguishing it from primary hyperparathyroidism to avoid unnecessary treatments, including parathyroidectomy 3.
• FHH is typically a benign condition characterized by elevated serum calcium, low urinary calcium excretion, and non-suppressed circulating levels of parathyroid hormone (PTH), usually requiring no intervention 4.
• However, in some cases, FHH may require treatment, such as the use of a low-calcium formula and cinacalcet to modify PTH levels and improve the biochemical profile 4.

Treatment Options

Treatment options for FHH and other inherited hypercalcemia disorders include:

• Conventional calcium-lowering therapy, although this may not be effective in all cases 5.
• Cinacalcet, which can be used to modify PTH levels and improve the biochemical profile 4, 5.
• Salmon calcitonin nasal spray and furosemide tablets, which may be used to treat hypercalcemia and hyperparathyroidism 5.
• Parathyroidectomy, although this is not usually recommended for FHH patients as it may not alleviate hypercalcemia 5, 6.

Counseling and Diagnosis

Counseling and diagnosis are crucial in managing inherited hypercalcemia disorders.

• Family studies and genetic testing can help identify the underlying cause of FHH and other inherited hypercalcemia disorders 4, 7, 5.
• Laboratory investigations, such as serum calcium and PTH levels, and urinary calcium excretion, can help diagnose FHH and distinguish it from primary hyperparathyroidism 4, 7, 5.
• Recognition of FHH is important to avoid unnecessary parathyroid surgery and to respond effectively to severe neonatal primary hyperparathyroidism occasionally seen in such kindred 3, 6.