噻嗪类利尿剂常有助于发现原发性甲状旁腺功能亢进

芝加哥——来自美国明尼苏达州罗切斯特市梅奥医院的一项回顾性分析表明，在因高钙血症停用噻嗪类利尿剂的患者中，超过一半的患者即便在停药后高钙血症仍然存在，并且最终会被诊断为原发性甲状旁腺功能亢进（PHP）。

Robert Wermers博士

在国际内分泌学会和美国内分泌学会联合会议上，梅奥诊所内分泌、糖尿病、代谢与营养科的内分泌医生Robert Wermers博士报告称，这项研究总共分析了220例于1992~2010年被诊断为与噻嗪类药物相关的高钙血症患者。患者的中位年龄为68岁，女性占86%（190例）。

81例（37%）患者停用了噻嗪类药物； 49例（60%）高钙血症仍然存在，其中43例（88%）后来被诊断为PHP。研究者称，这表明“在服用噻嗪类利尿剂期间出现了高钙血症的患者中，PHP较为常见。”

与整个患者人群（220例）相比，被诊断为PHP的患者在服用噻嗪类药物期间最大血钙值略高（平均值10.9 vs. 10.7 mg/dL），发现高钙血症时噻嗪类药物的用药时间更短（中位值2.9 vs. 3.9年）。两组均有超过80%的患者为女性，发现高钙血症时的平均年龄大约为67岁。开始接受噻嗪类药物治疗之前两组患者的血钙水平均正常（两组的中位值均为9.7 mg/dL）。

在虽然出现了高钙血症但仍继续服用噻嗪类药物的139例（63%）患者中，71例（51%）仍然存在高钙血症，7例（5%）最终被诊断为PHP，68例（48.9%）血钙水平恢复正常。

与噻嗪类药物相关的高钙血症的总发生率约为每100,000人年中有17例。在年龄介于65~74岁的女性中发生率最高，约为314.3例/100,000人年。该病发生率从20世纪90年代中期开始趋于上升，并于1999年达到高峰，大约为31.7例/100,000人年，可能是因为当时发布的指南呼吁增加骨质疏松症的筛查。到了2010年，发生率约为20例/100,000人年。

Wermers博士说，这些PHP患者很可能在开始使用噻嗪类药物之前就已经存在亚临床PHP了，并且PHP也有可能与他们的高血压相关。这项研究表明，会减少钙排泄的噻嗪类药物治疗很可能有助于发现PHP。“在我们的临床实践中，停用噻嗪类药物其实是比较常见的，我们往往会发现停药后血钙水平并没有恢复正常。现在有了研究数据来证实我们的临床印象。”

Wermers博士在会上指出，我们在开具噻嗪类药物处方时应该记住这一研究结果。几乎对于所有患者，开具噻嗪类药物都是为了治疗高血压。在这项研究中高钙血症只是一个偶然发现；所有患者都没有任何症状表现。年龄较大的女性发生PHP的风险最高，手术是常用治疗。

研究者声明无相关利益冲突，该研究项目没有接受任何外部资助。

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By: M. ALEXANDER OTTO, Cardiology News Digital Network

CHICAGO – More than half of patients who discontinue thiazide diuretics due to hypercalcemia will remain hypercalcemic even after stopping the drugs, and will eventually be diagnosed with primary hyperparathyroidism, according to a retrospective review from the Mayo Clinic in Rochester, Minn.

Those patients probably have subclinical primary hyperparathyroidism (PHP) disease before starting thiazides, and it may have contributed to their hypertension. In the study, PHP was likely unmasked by thiazide treatment, which reduces calcium excretion. "In our clinical practice, it’s not uncommon for us to stop thiazides, and then find calcium levels don’t normalize. Now we have data to confirm our clinical impression," said senior investigator Dr. Robert Wermers, an endocrinologist in the departments of endocrinology, diabetes, metabolism and nutrition at Mayo.

The finding is something to keep in mind when prescribing thiazides. In almost all patients, they were prescribed for hypertension. Hypercalcemia was an incidental finding in the study; none of the patients were symptomatic. Older women were most at risk for PHP, and surgery was the usual treatment, he said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

In all, the team reviewed 220 patients diagnosed with thiazide-associated hypercalcemia between 1992 and 2010. They were a median of 68 years old; 190 (86%) were women.

Eighty-one (37%) of those patients were taken off the drug; hypercalcemia persisted in 49 (60%) patients, of whom 43 (88%) were subsequently diagnosed with PHP.

The findings suggest that "primary hyperparathyroidism is common in patients who develop hypercalcemia while taking thiazide diuretics," the investigators said.

Compared with the overall patient population of 220, those who were diagnosed with PHP had a slightly higher maximum serum calcium while on thiazides (mean 10.9 vs. 10.7 mg/dL) and had been on thiazides a shorter period of time when hypercalcemia was detected (median 2.9 vs. 3.9 years). More than 80% of the patients in both groups were women, and the mean age at onset of hypercalcemia was about 67 years. Serum calcium was normal in both groups before thiazide treatment (median 9.7 mg/dL for both groups).

Of the 139 (63%) patients who stayed on thiazides despite hypercalcemia, 71 (51%) remained hypercalcemic, seven (5%) were eventually diagnosed with PHP, and calcium normalized in 68 (48.9%).

The overall incidence of thiazide associated hypercalcemia was 17 cases per 100,000 person-years. The highest rate was 314.3/100,000 person-years in women 65-74 years old. The incidence started climbing in the mid-1990s and peaked in 1999 at 31.7 cases per 100,000 person-years, perhaps because the guidelines released at the time that called for increased osteoporosis screening. In 2010, the incidence was about 20 cases per 100,000 person-years.

The investigators have no disclosures, and had no outside funding for the project.