Thiazide Treatment in Primary Hyperparathyroidism—A New Indication for an Old Medication?

Tsvetov, Gloria; Hirsch, Dania; Shimon, Ilan; Benbassat, Carlos; Masri-Iraqi, Hiba; Gorshtein, Alexander; Herzberg, Dana; Shochat, Tzippy; Shraga-Slutzky, Ilana; Diker-Cohen, Talia

doi:10.1210/jc.2016-2481

Cited by 32 publications

(11 citation statements)

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“…If thiazides do have a significant impact on plasma calcium we would have expected to see greater reduction in calcium at 1 year after their cessation in our non-surgical patients on thiazide diuretics at diagnosis (thiazides were discontinued in all patients in this cohort). However, no significant difference was observed lending further evidence to the contention ( 9 ) that the diagnosis of PHPT should not lead to automatic discontinuation of thiazides.…”

Section: Discussionmentioning

confidence: 73%

“…The initial recommended screening test to exclude FHH, in addition to a full family history, is the urine calcium creatinine clearance ratio (CCCR), which should be >0.01 in patients with PHPT ( 8 ). Another potential contributor to hypercalcaemia in patients with probable PHPT is thiazide diuretic use, although recent reports suggest the impact to be minimal and paradoxically thiazides may even reduce blood PTH concentrations ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

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Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre’s experience

Reid

Muthukrishnan

Patel

et al. 2018

Endocrine Connections

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ObjectivePrimary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT.DesignRetrospective cohort study.PatientsPHPT assessed between 2006 and 2014 (n = 611) in a university hospital.MeasurementsSymptoms, clinical features, biochemistry, neck radiology and surgical outcomes.ResultsFatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035).ConclusionsClinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre’s experience

Reid

Muthukrishnan

Patel

et al. 2018

Endocrine Connections

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show abstract

“…In principle, thiazide diuretics, i.e., those most commonly used in hypertension, alone or in combination with other pharmacological classes (ACE inhibitors, angiotensin receptor blockers, and beta-blockers) are regarded not to usually increase, but rather decrease renal excretion of calcium ions [29]. Hence their participation in bone mineral depletion processes should be deemed to occur less likely when compared to that attributed to the loop diuretics (furosemide, torsemide, and etacrinic acid) .…”

Section: Discussionmentioning

confidence: 99%

Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study

Vecchis

Ariano

Biase³

et al. 2017

J Clin Med Res

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BackgroundAn alleged association of chronic use of thiazide diuretics with an increased risk of bone fragility fractures has been highlighted by a relatively recent prospective cohort study. However, the concept that thiazides exert a beneficial effect on osteoporosis is still a predominant view. This effect would be mediated by the decrease in renal clearance of calcium ions, a pharmacological feature recognized for a long time now to this class of drugs, as opposed to the increase in calcium urinary excretion attributed instead to loop diuretics, i.e. furosemide and similar drugs. The purpose of this retrospective study was to attempt to clarify whether regular use of thiazide diuretics as antihypertensive therapeutics is associated with a significantly increased risk of osteoporotic fractures in female patients aged 65 or over.MethodsIn this two-center retrospective study, we followed up a cohort of female patients with (n = 80) and without (n = 158) thiazide-induced hyponatremia.ResultsA total of 48 osteoporotic fractures were recorded during a median follow-up period of 57.5 months. By means of univariate regression analysis, an association was found between thiazide-induced hyponatremia and increased risk of vertebral fractures (odds ratio (OR): 7.6; 95% confidence interval (CI): 3.755 - 15.39; P < 0.0001). Multivariate regression analysis, however, showed that age (OR: 1.823; 95% CI: 1.211 - 2.743) and body mass index (OR: 0.156; 95% CI: 0.038 - 0.645) were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatremia and risk of fracture was noticeable in the final model.ConclusionsBecause thiazide-induced hyponatremia was associated with spinal fractures in univariate but not multivariate analysis, a possible explanation is that hyponatremia may be a confounder of the relation between body mass and spinal fractures. Indeed, reduced body mass especially among elderly women with small body build may confer heightened risk of thiazide-induced hyponatremia because of decreased bone sodium available for exchange with the serum sodium. Thus, occurrence of hyponatremia could only serve as an indirect surrogate marker for osteoporosis risk.

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“…In principle, thiazide diuretics, i.e., those most commonly used in hypertension, alone or in combination with other pharmacological classes (ACE inhibitors, angiotensin receptor blockers, beta-blockers) are regarded not to usually increase, but rather decrease renal excretion of calcium ions ( 28 ). Hence their participation in bone mineral depletion processes should be deemed to occur less likely when compared to that attributed to the loop diuretics (furosemide, torsemide, etacrinic acid).…”

Section: Discussionmentioning

confidence: 99%

Chronic antihypertensive therapy with thiazide diuretics in older women and risk of osteoporotic vertebral fractures: A recently much-debated association

Rdv¹,

Ariano²,

A³

et al. 2017

Preprint

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Background An alleged association of chronic use of thiazide diuretics with an increased risk of bone fragility fractures has been highlighted by a relatively recent prospective cohort study (Am J Med. 2016 Dec; 129(12):1299-1306. However, the concept that thiazides exert a beneficial effect on osteoporosis is still a predominant view. This effect would be mediated by the decrease in renal clearance of calcium ions, a pharmacological feature recognized for a long time now to this class of drugs , as opposed to the increase in calcium urinary excretion attributed instead to loop diuretics, i.e. furosemide and similar drugs . The purpose of this retrospective study is to attempt to clarify whether regular use of thiazide diuretics as antihypertensive therapeutics is associated with a significantly increased risk of osteoporotic fractures in female patients, aged over 70 years. Methods In this two-centre retrospective study, we followed up a cohort of female patients with (n= 80) and without (n= 158) thiazide-induced hyponatraemia. Results A total of 48 osteoporotic fractures was recorded during a median followup period of 57.5 months. By means of univariate regression analysis, an association was found between thiazide-induced hyponatraemia and increased risk of vertebral fractures (Odds ratio [OR]: 7.6; 95% confidence interval p <0.0001). Multivariate regression analysis, however, showed that age (OR: 1.823; 95% CI: 1.211 to 2.743) and body mass index (OR: 0.156; 95% CI: 0.038 to 0.645) were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatraemia and risk of fracture was noticeable in the final model.

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Thiazide Treatment in Primary Hyperparathyroidism—A New Indication for an Old Medication?

Abstract: Thiazides may be effective even at a dose of 12.5 mg/d and safe at doses of up to 50 mg/d for controlling hypercalciuria in patients with PHPT and may have an advantage in decreasing serum parathyroid hormone level. However, careful monitoring for hypercalcemia is required.

Cited by 32 publications

References 18 publications

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre’s experience

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre’s experience

Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study

Chronic antihypertensive therapy with thiazide diuretics in older women and risk of osteoporotic vertebral fractures: A recently much-debated association

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