From the Guidelines
Hydrochlorothiazide (HCTZ) can indeed cause hypercalcemia due to its effect on reducing urinary calcium excretion and increasing calcium reabsorption in the kidneys. This is a crucial consideration in patients taking HCTZ, particularly those with underlying conditions that predispose them to calcium abnormalities, such as hyperparathyroidism, malignancy, or excessive vitamin D intake 1. The mechanism by which HCTZ leads to hypercalcemia involves its action as a thiazide diuretic, which enhances calcium reabsorption in the distal tubules of the kidneys.
Key points to consider in the management of patients on HCTZ include:
- Monitoring for symptoms of hypercalcemia, such as fatigue, muscle weakness, constipation, nausea, and cognitive changes.
- Regular blood tests to check calcium levels, especially in high-risk patients.
- Considering dose reduction or switching to a different class of antihypertensive medication if hypercalcemia develops.
- Being aware that loop diuretics like furosemide have the opposite effect on calcium handling and may be considered as alternatives in patients with calcium concerns.
It's also important to note that the dosages of HCTZ associated with a hypocalciuric effect, as mentioned in the medical management of kidney stones guideline, include 25 mg orally, twice daily, or 50 mg orally, once daily 1. However, the primary concern in the context of hypercalcemia is the potential for HCTZ to increase serum calcium levels, which necessitates careful monitoring and management.
From the FDA Drug Label
Parathyroid Disease Calcium excretion is decreased by thiazides, and pathologic changes in the parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy.
Hydrochlorothiazide (HCTZ) can cause hypercalcemia, as it decreases calcium excretion and has been associated with pathologic changes in the parathyroid glands, leading to hypercalcemia and hypophosphatemia in some patients on prolonged therapy 2.
From the Research
Hydrochlorothiazide (HCTZ) and Hypercalcemia
- HCTZ can cause hypercalcemia in certain individuals, particularly those with specific types of hypercalciuria 3.
- Studies have shown that HCTZ can increase serum calcium levels in anuric patients, especially those with high parathyroid hormone (PTH) levels 4.
- The mechanism of HCTZ-induced hypercalcemia is not fully understood, but it may be related to the drug's effect on renal calcium handling and PTH secretion 5.
Effects of HCTZ on Calcium Excretion
- HCTZ can decrease urinary calcium excretion in patients with idiopathic hypercalciuria, which may lead to increased serum calcium levels 6.
- In patients with renal hypercalciuria, HCTZ can cause an exaggerated natriuretic and calciuric response, which may contribute to hypercalcemia 7.
Clinical Implications
- Patients taking HCTZ should have their electrolytes frequently checked, especially those on calcium supplements 3.
- HCTZ may have a beneficial role in the diagnosis and management of patients with primary hyperparathyroidism and hypercalciuria 5.
- Caution is required when interpreting the results of HCTZ therapy in patients with hypercalcemia, as the relationship between HCTZ and PTH secretion is complex and not fully understood 4.