Abstract and Introduction
Abstract
Context: Patients with primary hyperparathyroidism (PHPT) can present with variable signs, symptoms, and end-organ effects. Clinical practice guidelines influence referral for consideration of parathyroidectomy.
Objective: This study compared the demographic, biochemical, and symptom profile and examine indications for surgery in patients older than 50 years who underwent parathyroidectomy to determine how changes to current guidelines may affect recommendations for parathyroidectomy.
Methods: A retrospective review was conducted of patients age 50 years or older who underwent initial parathyroidectomy for sporadic PHPT from 2012 to 2020. Patients were classified by indications for surgery per guideline criteria (classic, asymptomatic, and no criteria met) and age group (AG): 50 to 59 years; 60 to 69 years; 70 years or older. Patients were treated at a high-volume tertiary medical center by endocrine surgeons.
Results: Of 1182 patients, 367 (31%) classic and 660 (56%) asymptomatic patients met the criteria for surgery. The most common indications for surgery were extent of hypercalcemia (51%), osteoporosis (28%), and nephrolithiasis (27%). Of the 155 (13%) patients who did not meet the criteria, neurocognitive symptoms (AG1: 88% vs AG2: 81% vs AG3: 70%; P = .14) and osteopenia (AG1: 53% vs AG2: 68% vs AG3: 68%; P = .43) were frequently observed regardless of patient age. If the age threshold of younger than 50 years was expanded to 60, 65, or 70 years, an additional 61 (5%), 99 (8%), and 124 (10%) patients in the entire cohort would have met the guideline criteria for surgery, respectively.
Conclusion: Expanding current guidelines for PHPT to include a broader age range, osteopenia, and neurocognitive symptoms may allow for earlier surgical referral and evaluation for definitive treatment.
Introduction
Primary hyperparathyroidism (PHPT) is a condition that results in hypercalcemia due to inappropriate autonomous secretion of parathyroid hormone (PTH) by abnormal parathyroid gland(s). The diagnosis of PHPT is biochemical but remains underdiagnosed in patients with high serum calcium levels.[1–3] PHPT can negatively affect bone mineral density (BMD) and renal function, leading to fragility fractures, reduced glomerular filtration rate (GFR), and nephrolithiasis.[4] Symptoms associated with PHPT include musculoskeletal, gastrointestinal, and/or neurocognitive symptoms; the severity of these nonspecific, patient-reported symptoms can be highly variable. Parathyroidectomy is the only cure for PHPT, with reported cure rates greater than 95% and low rates of procedure-specific complications, such as recurrent laryngeal nerve injury and/or permanent hypoparathyroidism.[5–8] Parathyroidectomy has been shown to improve sequelae of PHPT in nearly all facets of the disease.[5,9–17] Parathyroidectomy is a procedure that is commonly performed in the outpatient setting with low rates of morbidity and rare mortality.[7,18–21] Despite this, previous studies have shown that referral for surgery is likely guided by published societal clinical practice guidelines and PHPT remains underdiagnosed and undertreated.[22–27]
Current consensus guidelines, which include those from the Fourth and Fifth International Workshops and the American Association of Endocrine Surgeons (AAES), classify PHPT into classic and asymptomatic categories based on specific disease features.[22,24,28,29] Surgery is recommended for patients with symptomatic or "classic" PHPT (nephrolithiasis and fragility fractures), whereas other sequelae of PHPT, including reduced BMD, nephrocalcinosis, hypercalciuria, and reduced GFR, are considered "asymptomatic." Indications for parathyroidectomy in patients with asymptomatic disease per the Fourth International Workshop include (1) serum calcium greater than 1.0 mg/dL above the upper limit of normal; (2) BMD by dual-energy x-ray absorptiometry T score less than −2.5 at any site; (3) radiographic evidence of vertebral fracture; (4) 24-hour urine calcium greater than 400 mg/day and increased risk of stone formation; (5) presence of nephrolithiasis or nephrocalcinosis on imaging; and/or (6) age younger than 50 years.[22] The 2022 International Workshop revised recommendations for parathyroidectomy based on hypercalciuria to a threshold of greater than 250 mg/day for women and more than 300 mg/day for men.[29]
It is important to note that parathyroidectomy should not be limited to symptomatic patients or asymptomatic patients who fulfill these guidelines. Justifications to support the current age recommendation of 50 years for patients with asymptomatic PHPT are largely based on potential consequences of long-term PHPT and data that suggest disease progression is more likely in younger patients than older patients.[30] Age 50 years has remained constant in recent guidelines, even as life expectancy in the United States has increased by almost 10 years in recent decades.[31] Increasing life expectancy may also have an effect on the progression of BMD in patients with PHPT, perhaps particularly those with osteopenia, given that BMD has been shown to decline at the hip and distal radius when no intervention has occurred for more than 10 years since onset of disease.[13,32–35]
In addition, while the presence of neurocognitive symptoms, including anxiety, depression, memory, concentration, and fatigue, were acknowledged both in the 2014 and 2022 International Workshop guidelines, they were not considered a strict indication for surgery.[22] Some studies, however, have demonstrated improvement in these symptoms following parathyroidectomy.[12,14,36] Based on these data, the AAES guidelines endorse a strong recommendation for parathyroidectomy in the setting of patients with neurocognitive symptoms "attributable to PHPT."[24] Furthermore, in a recent systematic review of 31 studies that examined quality of life in patients with PHPT, the majority (87%) demonstrated significant improvement following curative parathyroidectomy.[17,22–24]
We hypothesized that among patients older than 50 years who underwent parathyroidectomy for asymptomatic PHPT, not all patients would meet the current guideline criteria, and that broadening the age criterion and criteria for other common sequelae of PHPT would increase the number of patients who may derive benefit from curative parathyroidectomy. Therefore, the aim of this study was to compare the demographic, biochemical, symptom profile, and indications for surgery in patients older than 50 years who underwent parathyroidectomy at our institution, to determine how changes to the current guidelines may affect recommendations for parathyroidectomy, as these findings may guide decision-making among patients and their health care team. Potential differences in symptom profile among patients who did not meet the guideline criteria and underwent parathyroidectomy also were assessed.
J Endo Soc. 2023;7(9) © 2023 Endocrine Society
