Thiazides, a Viable Treatment for Primary Hyperparathyroidism?

When surgery is not an option, thiazide diuretics--an old drug class with complicated side effects--may offer an effective alternative for some patients.

Surgery remains the best solution for patients with primary hyperparathyroidism (PHPT). However, certain patients--either because they’re elderly, have comorbid conditions, or simply refuse to consider surgery—need another treatment option. For these nonoperable patients, a type of drug that physicians previously avoided may be a choice after all--thiazides.

Typically, thiazide diuretics have been given to patients with hypercalciuria whose cause is not known. However, when patients have hypercalciuria as a result of PHPT, thiazides were not offered because of the concern that blood calcium levels would rise.

Thiazides may offer alternative to surgery for hyperparathyroid disease

To test this theory, an Israeli team at Rabin Medical Center and Tel Aviv University conducted a retrospective analysis of the medical records of 72 patients--58 of them female--with PHPT who had been treated with thiazides for either hypercalciuria or hypertension.1 They found that the thiazide medication lowered urine calcium levels but did not appear to raise serum calcium levels.

 “This study was prompted by the controversy surrounding the use of thiazide in patients with PHPT,” wrote the authors in the study’s discussion section.

“We found that in patients with PHPT and hypercalciuria who are ineligible for or have failed surgery, treatment with thiazide diuretics can successfully decrease urinary calcium excretion without inducing a significant change in serum calcium level regardless of the dose used (12.5-50 mg/day),” Tsvetor and his team stated in their paper1; they did not respond to a request for comment.

Out of 11 patients in the study whose calcium levels already were elevated at the start (11.5mg/dL or higher), 9 pateints experienced a decrease after receiving thiazide treatment, while 2 saw their blood calcium levels increase and required surgery at a later date.1

Among the 60 patients whose blood calcium level was lower than 11.5 mg/dL at the start of the study, only 8 experienced a rise in blood calcium while on thiazides.

In light of these results, the scientists concluded that thiazide appeared effective at the standard daily dose of 12.5 mg and would be safe at doses up to 50 mg per day.

Thiazide therapy may be a good alternative to surgery for 2 particular subsets of patients1 with a baseline level as follows:

1)   Blood calcium level of at least 11.5 mg/dL or

2)   Urinary calcium level of at least 400 mg/day.

However, the authors urge caution due to the experience of 2 patients who started with a high blood calcium level and whose calcium levels rose even higher during treatment.  

“This finding emphasizes the need for careful monitoring of all patients with PHPT who are prescribed thiazides,” they wrote. “Maximal hypercalcemia in these patients was reached at least 5 months after initiation of thiazide, which is considerably earlier than the 1 year or more from onset of thiazide use reported in a previous observational study2 of the incidence of thiazide-associated hypercalcemia in the general population.”

The Takeaway: Best Practice Insights

Scott Isaacs, MD, FACP, FACE, an Atlanta endocrinologist on the faculty at Emory University School of Medicine, found the study’s results interesting given the typical practice of avoiding thiazides when treating patients with PHPT.

“They actually didn’t make [blood calcium levels] worse when you’d think they would,” he told EndocrineWeb. Nevertheless, he doesn’t advocate taking a blanket approach to treating PHPT patients with thiazides.

“I would do it with extreme caution,” he said. “There are still plenty of other reports out there--in every textbook--that [thiazides] can cause problems.”

Dr. Isaacs advocated that endocrinologists consider the following for their PHPT patients:

Always consider surgery first. “It’s the best option,” he said. “[Thiazides] are more palliative.” For patients eligible for surgery but who simply don’t want it, he would try to convince them otherwise based on the benefits of surgery and the known risks of thiazides. Dr. Isaacs said he’d only consider prescribing thiazides to patients who absolutely could not have surgery for medical reasons.

Carefully monitor urine and blood calcium levels if prescribing thiazides. He suggests getting baseline levels of both, then rechecking them two to four weeks after beginning the medication and then again after about three months.

Use the smallest dose possible. Despite the study’s participants getting up to 50 mg per day, Dr. Isaacs doesn’t recommend it. “I never use 50 mg because I don’t think 50 mg is a safe dose,” he stated, citing potential side effects such as low potassium levels and dehydration.

Urge patients to watch for side effects of hypercalcemia. Dr. Isaacs mentioned frequent urination, thirst, depression, and upset stomach as possible signifiers of a blood calcium level that’s too high, although he acknowledges those are nonspecific symptoms attributable to a range of conditions.

The authors noted a few limitations to the study.1 As it was retrospective, they did not know if the subjects had experienced any of thiazide’s possible side effects, such as hyponatremia or kidney stones. Also, there was no accurate information about the subjects’ dietary calcium intake, although all had been advised not to limit their calcium intake. 

Continue Reading:
Does Hyperparathyroidism Surgery Affect Patients’ Bone Mineral Density?
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