The Efficacy and Safety of Medical and Surgical Therapy in Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomaticThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Management of Primary Hyperparathyroidism

“…The reader is referred to a review that presents these results in detail. (2) In tabular form (Table 1), we summarize the papers reviewed, the characteristics of the study subjects, and a summary of the results. The limited evidence available does not provide with any confidence evidence that surgery is associated with an effect on quality of life, occurrence of kidney stones, or renal function.…”

“…The reader is referred to the review that presents these results in detail including a discussion of adverse events. (2) In tabular form (Table 3), we summarize the papers that were reviewed, the characteristics of the study subjects, and the results. Because of limitations in data quality and only inferential effect on patient important outcomes such as fracture, there are no specific GRADEd recommendations for medical therapy of PHPT.…”

Efficacy of antiresorptive agents bisphosphonates and denosumab in mitigating hypercalcemia and bone loss in primary hyperparathyroidism: A systematic review and meta-analysis

“…A recent paper performed meta-analyses of all available medical and surgical modalities for PHPT in comparison to placebo control and excluded non-RCT studies where endpoint effects were compared with baseline ( 33 ). The parameters included in the meta-analysis were BMD, PTH, and calcium, although for BMD, only a single dataset was used for performing the meta-analysis.…”

Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop

“…In those with asymptomatic PHPT, however, criteria have been developed based upon the presence of target organ involvement and evidence for improvement after successful surgery. To reconsider this topic, as comprehensively as possible, two approaches were employed: a systematic review utilizing GRADE methodology ( 7 ) and a narrative review that incorporated noteworthy information that could not be included in the systematic review. ( 6 ) In addition, a task force designated to consider specific aspects of parathyroid surgery helped to identify advances in technical aspects and outcomes of parathyroid surgery.…”

“…Four papers provide an evidence-based review of the Epidemiology, Pathophysiology, and Genetics of PHPT (3) ; Classical and Nonclassical Manifestations (4) ; Surgical Aspects (5) ; and Management (6) ; as well as one document following GRADE methodology for surgical and medical management of PHPT. (7) A paper describing the methodology of the evidence-based reviews is also included in this series. (8) The summary statement maintains or revises the guidelines, based upon the expanded database of evidence currently available.…”