24-hour Urine Calcium Predicts Reduced Fracture Incidence and Improved BMD After Surgery for Primary Hyperparathyroidism.

CONTEXT: Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with impact on fracture incidence and bone mineral density after surgery have not been firmly established. OBJECTIVE: To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT). DESIGN: Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register. SETTING: Tertiary referral center. PATIENTS OR OTHER PARTICIPANTS: 709 patients with successful parathyroidectomy for pHPT, and 2,112 controls matched on sex, age, and municipality were included in the study. MAIN OUTCOME MEASURES: Fracture incidence, absolute change and ≥2.77% increase in bone mineral density of femoral neck, L2-L4 and distal third of radius at 1-year follow-up. RESULTS: Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (IRR for the highest tertile 220- mg/d 0.29, CI 95% 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin and adenoma weight were all associated with bone mineral density recovery after surgery. CONCLUSIONS: 24-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT.

Reduced fracture incidence in patients having surgery for primary hyperparathyroidism.

OBJECTIVE: The indication of surgery in primary hyperparathyroidism has been controversial, as many patients experience mild disease. The primary aim was to evaluate fracture incidence in a contemporary population-based cohort of patients having surgery for primary hyperparathyroidism. The secondary aim was to investigate whether preoperative serum calcium, adenoma weight or multiglandular disease influence fracture incidence. DESIGN: A retrospective cohort study with population controls. Primary outcomes, defined by discharge diagnoses and prescriptions, were any fracture and fragility fracture, secondary outcomes were multiple fractures anytime and osteoporosis. Subjects were followed 10 years pre- and up to 10 years postoperatively (or 31 December 2015). Multiple events per subject were allowed. Fracture incidence rate ratios (IRRs) for patients pre- and postoperatively were tabulated and evaluated with mixed-effects Poisson regression. Secondary outcomes were evaluated using conditional logistic regression. PATIENTS: A Swedish nationwide cohort of patients having surgery for primary hyperparathyroidism (n = 5009) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery between 2003 and 2013 was matched with population controls (n = 14,983). Data were cross-linked with Statistics Sweden and the National Board of Health and Welfare. MEASUREMENTS: Preoperative serum calcium and adenoma weight at pathological examination. RESULTS: Patients had an increased incidence rate of any fracture preoperatively, IRR 1.27 (95% confidence interval: 1.11-1.46), highest in the last year before surgery. Fracture incidence was not increased postoperatively. Serum calcium, adenoma weight and multiglandular disease were not associated with fracture incidence. CONCLUSIONS: Fracture incidence is higher in patients with primary hyperparathyroidism but is normalized after surgery.

Predictors of multiglandular disease in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (pHPT) is caused by single- or multiglandular disease (MGD). Patients with MGD have an increased risk of complications at surgery and for persistence and recurrence after surgery. The study evaluated whether preoperative clinical and biochemical characteristics could predict MGD in patients with pHPT. METHODS: We retrospectively evaluated patients operated 1989-2013 for first-time, non-hereditary pHPT. MGD was defined in patients with more than one pathological gland excised at surgery or with persistent hypercalcemia after the excision of a single pathological parathyroid gland, confirmed by histopathology. Clinical and biochemical variables were compared in patients with single- and multiglandular disease. Logistic regression was used to identify variables predicting MGD, yielding odds ratios (OR) with 95% confidence intervals (CI). RESULTS: There were 707 patients, of which 79 (11%) had MGD. Patients with MGD were more likely to have negative sestamibi scintigraphy than patients with single-gland disease, 15 of 49 (31%) vs. 70 of 402 (17%; p = 0.03), to suffer from diabetes (12 of 74, 16%) vs. 45 out of 626 patients (7.2%; p < 0.01) and had lower preoperative levels of urinary calcium (3.80 vs. 4.44 mmol/L; p = 0.04). Multivariable analysis identified negative scintigraphy (OR 2.42; 95% CI 1.18 to 4.79), diabetes (OR 2.75; 95% CI 1.31 to 4.97) and elevated levels of osteocalcin (OR 3.79, 95% CI: 1.75 to 8.21) as predictors of MGD. CONCLUSION: Negative sestamibi scintigraphy, diabetes and elevated osteocalcin levels were predictors of MGD.

Cardiac arrest with vagal stimulation during intraoperative nerve monitoring.

BACKGROUND: Intraoperative neuromonitoring (IONM) is widely used during thyroid surgery. During both intermittent and continuous IONM stimulation of the vagus nerve is performed. This has previously been reported to be safe. METHODS: We present our findings based on the case reports of 2 patients. RESULTS: IONM of the recurrent laryngeal nerve (RLN), following the standards of the International Neuromonitoring Study Group, was conducted in 2 patients, one undergoing thyroid surgery and the second parathyroid surgery. In both cases, after dissection and stimulation of the vagus nerve on 1 mAmp, the patients became asystolic. Resuscitation efforts were successful in both patients. CONCLUSION: These 2 cases demonstrate that stimulation of the vagus nerve during IONM can lead to profound cardiac events. Consideration should be given to these potential complications when utilizing IONM. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2419-E2420, 2016.

Presentation and Outcomes After Surgery for Primary Hyperparathyroidism During an 18-Year Period.

PURPOSE: The objective of this study is to analyze whether the trend towards operating on patients with less severe primary hyperparathyroidism (pHPT) than earlier is reflected in a change of preoperative presentation and surgical outcome. METHODS: In this longitudinal cohort study, patients with pHPT subjected to first time surgery were compared in three time periods: 1989-1994, 1995-2000, and 2001-2006 in this longitudinal cohort study. RESULTS: There were 404 patients. Median levels of preoperative ionized calcium were lower in 2001-2006 compared to 1989-1994; 1.45 versus 1.50 versus 1.45 mmol/L; p < 0.001. Preoperative parathyroid hormone levels in patients with parathyroid adenoma were lower in 2001-2006 than in 1989-1994; 10.0 versus 11.6 pmol/L; p 0.04. Median preoperative bone mineral density, BMD, in the whole cohort did not differ between time periods. Median pre- and postoperative glomeruli filtration rate, GFR, and 25-hydroxy-vitamin D3 remained unchanged between period 1 and period 3. Adenoma weight was lower in 2001-2006 than 1989-1994; 0.70 versus 0.50 g; p 0.04. Cure rate did not change during observation time. There was no evidence for differences in change of BMD (femoral neck) after surgery between period 2 and 3 1995-2000 and 2001-2006, 0.798 versus 0.795 g/cm(2); p 0.67. GFR did not change significantly between 1989-1994 and 2001-2006, 74 versus 77 mL/min; p 0.43. CONCLUSIONS: A significant change towards operating patients with smaller adenomas and lower preoperative calcium levels was evident throughout the observation period, but this did not correlate with differences in preoperative renal or skeletal function. We found no evidence for a change of postoperative renal function or skeletal function during observation time.

Results of a Fifteen-Year Follow-up Program in Patients Operated with Unilateral Neck Exploration for Primary Hyperparathyroidism.

BACKGROUND: Since the introduction of unilateral parathyroidectomy for primary hyperparathyroidism (pHPT) it has been debated wherever this approach is associated with greater long-term risk for recurrence compared to bilateral neck exploration. METHODS: This is a prospective study based on a structured 15-year follow-up program in patients with non-hereditary, sporadic pHPT, undergoing first time surgery with unilateral or focused neck exploration (unilateral procedures), with the use of intraoperative PTH (iOPTH) between 1989 and 2010. RESULTS: 292 patients were analyzed. The median age of the patients was 66 years [interquartile range (IQR) 57-75], and 234 (80.4%) were female. The median preoperative level of total calcium was 2.74 mmol/L (IQR 2.63-2.85 mmol/L) and the median PTH level was 10 pmol/L (IQR 7.4-14 pmol/L). The median follow-up time was 5 years (IQR 1-10 years). Some 275 patients were followed for 1 year (94.2%/275 person-years/5 patients deceased), 164 for 5 years (56.2%/820 person-years/31 patients deceased), 70 for 10 years (24.0%/700 patient-years/57 patients deceased) and 51 (17.5%/765 patient-years/69 patients deceased) for 15 years after surgery. Three patients (1.1%) had signs of persistent disease. One patient recurred in pHPT at 5 years postoperatively during 15 years of follow-up. Histopathology indicated solitary parathyroid adenoma at primary surgery. CONCLUSION: Patients with pHPT operated with unilateral procedures and iOPTH, had a low risk for long-term recurrence during a 15 years follow-up program.

Vitamin d status in patients operated for primary hyperparathyroidism: comparison of patients from southern and northern europe.

Aim. The interaction between vitamin D deficiency and primary hyperparathyroidism (PHPT) is not fully understood. The aim of this study was to investigate whether patients with PHPT from Spain and Sweden differed in vitamin D status and PHPT disease activity before and after surgery. Methods. We compared two cohorts of postmenopausal women from Spain (n = 126) and Sweden (n = 128) that had first-time surgery for sporadic, uniglandular PHPT. Biochemical variables reflecting bone metabolism and disease activity, including levels of 25-hydroxy vitamin D3 (25(OH)D) and bone mineral density, BMD, were measured pre- and one year postoperatively. Results. Median preoperative 25(OH)D levels were lower, and adenoma weight, PTH, and urinary calcium levels were higher in the Spanish cohort. The Spanish patients had higher preoperative levels of PTH (13.5 versus 11.0 pmol/L, P < 0.001), urinary calcium (7.3 versus 4.1 mmol/L, P < 0.001), and heavier adenomas (620 versus 500 g, P < 0.001). The mean increase in BMD was higher in patients from Spain and in patients with vitamin D deficiency one year after surgery. Conclusion. Postmenopasual women with PHPT from Spain had a more advanced disease and lower vitamin 25(OH)D levels. Improvement in bone density one year after surgery was higher in patients with preoperative vitamin D deficiency.

Changing biochemical presentation of primary hyperparathyroidism.

PURPOSE: Patients with primary hyperparathyroidism, pHPT, present with milder symptoms than previously. Some, but not all studies, suggest that this change in clinical pattern also implies lower preoperative parathyroid hormone (PTH) and/or calcium levels and smaller adenomas. This is important since reports indicate that smaller adenomas are more difficult to detect on preoperative imaging, possibly increasing the risk of surgical failure. METHODS: There were 640 patients with histologically confirmed single-gland pHPT identified in a prospectively collected database. Median values of preoperative calcium, PTH, as well as adenoma weight were compared in three different time periods: 1990-1995, 1996-2000, and 2000-2007. Correlation between the preoperative levels of calcium and PTH and adenoma weight was calculated. RESULTS: Preoperative ionized calcium decreased significantly over time (p < 0.001). There was a positive correlation between preoperative PTH and adenoma weight (r = 0.32, p < 0.001). The magnitude of this correlation decreased over time. In women, adenoma weight decreased significantly over time (p = 0.03). Median (25th-75th percentile) adenoma weight in women was 750 (400-1,380) mg, 650 (350-1,205) mg, and 520 (305-1,065) mg in the first, second, and third period, respectively. CONCLUSION: From 1990 to 2007, there was a significant trend to operate pHPT patients with lower preoperative serum ionized calcium levels. In women, the adenoma weight decreased. This trend could potentially lead to decreased sensitivity in preoperative localization procedures.

Surgery for patients with primary hyperparathyroidism and negative sestamibi scintigraphy--a feasibility study.

BACKGROUND: We report the surgical treatment of a consecutive series of scan negative patients with the intention of unilateral parathyroid exploration with the aid of intraoperative quick PTH (qPTH). MATERIALS AND METHODS: The study included 35 consecutive sestamibi scan negative patients (27 women, eight men) with sporadic pHPT subjected to first time surgery. Median age was 70 years and median preoperative calcium level 2.8 mmol/L. RESULTS: Thirty-three patients had a histological diagnosis of a parathyroid adenoma (median weight 0.48 g [range 0.12 g-2.5 g]). Nineteen patients were explored bilaterally and 16 patients (46%) were operated unilaterally. The median operation time was 40 min in the unilateral group and 95 min in the bilateral group (p < 0.001). Three patients were treated for postoperative hypocalcemia after bilateral exploration versus none in the unilateral group (p = 0.23). With a minimum of 12 months of follow-up, 33 patients (94.3%) were cured. One case of recurrent HPT presented after bilateral exploration with visualization of four glands. One case of persistent HPT was observed after unilateral exploration. qPTH was predictive of operative failure in both patients. CONCLUSION: Forty-six percent of the patients in our study could be operated unilaterally with a total cure rate of 94%. Patients in the unilateral group had a significant shorter operation time and a lower incidence of postoperative hypocalcemia. In conclusion our investigation shows that limited parathyroid exploration can safely be performed on patients with negative sestamibi scintigraphy by the aid of qPTH.