Radioguided Parathyroidectomy in Patients with Familial Hyperparathyroidism

Background In patients with sporadic hyperparathyroidism (HPT), radioguided parathyroidectomy (RGP) has been shown to facilitate intraoperative localization of parathyroid glands, reduced operative time, and improve patient outcomes. No studies have focused on the role of RGP in patients with familial HPT. Methods Between 3/01 and 6/05, 419 patients underwent RGP. Nineteen had familial HPT, including 12 with Multiple Endocrine Neoplasia (MEN), and 94 had sporadic HPT with parathyroid hyperplasia. All patients were injected with sestamibi pre-operatively and a gamma probe was used intraoperatively. Radiotracer counts were recorded prospectively. Results In patients with familial HPT, the gamma probe detected all abnormal parathyroid glands with a mean in vivo radiotracer count of 157 ± 9% above background. Importantly, 5 patients (25%) had ectopic parathyroid glands localized by the probe in the thymus, thyroid and retroesophageal region. All resected hyperplastic parathyroid glands had ex vivo counts > 20%. All patients were cured after surgery with mean calcium and parathyroid hormone levels of 9.4 ± 0.1 mg/dl and 31 ± 7 pg/ml, respectively, and a mean hospital stay of 0.7 ± 0.1 days. In comparing the 2 groups, while patients with familial HPT had lower pre-operative parathyroid hormone levels, the ex vivo radiotracer counts were significantly higher. Conclusion RGP in patients with familial HPT is technically feasible and perhaps more sensitive than in patients with sporadic hyperplastic disease. The gamma probe efficiently localized all parathyroid glands including those in ectopic locations, and resulted in high cure rates and short hospital stays. RGP is a viable and useful technique in patients with familial HPT. Presented at the 59^th annual meeting of the Society for Surgical Oncology, San Diego, CA 24 March 2006     

Long-Term Outcome in Patients with Primary Hyperparathyroidism who Underwent Minimally Invasive Parathyroidectomy

Background  

Minimally invasive parathyroidectomy (MIP) has become a well-accepted treatment for selected patients with primary hyperparathyroidism (PHPT). However, few studies have evaluated long-term outcomes for this operative approach. We therefore chose to examine both the long-term symptom resolution and biochemical cure following MIP for PHPT.     

Durability of Focused Minimally Invasive Parathyroidectomy in Young Patients with Sporadic Primary Hyperparathyroidism

Background

Historically, multigland hyperplasia was believed to be the predominant cause of primary hyperparathyroidism (PHPT) in young patients, and hence a relative contraindication for minimally invasive parathyroidectomy. Recent studies, however, demonstrate that the most common aetiology across all age groups is a solitary functioning adenoma. The aim of this study was to compare long-term outcomes in young patients (≤45 years), especially those under 30 years of age, with their older counterparts (>45 years) following focused minimally invasive parathyroidectomy (FMIP).

Materials and Methods

Patients ≤45 years who underwent FMIP between January 1999 and December 2007 were identified from an endocrine surgery database and compared with a matched control group of patients >45 years old also undergoing FMIP within that time period. The patients’ most recent calcium levels (≥6 months postoperatively) were examined to establish recurrence rates. Recurrence was defined as an elevation of serum calcium more than 6 months after surgery following initial postsurgical normocalcemia.

Results

A total of 117 patients ≤45 years and 160 patients >45 years who underwent FMIP were examined. Follow-up calcium levels were available for 72% of patients. The median length of follow-up was 46 months. No recurrences were identified in both the younger and older cohort of patients; therefore, no statistically significant difference in rates of recurrence could be determined between age groups.

Conclusion

Recurrence of PHPT following FMIP is rare with no evidence of a higher incidence in younger patients. FMIP can be safely offered to young patients as a long-term durable treatment option.     

Outcomes of Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-analysis

Background

Parathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options.

Purpose

To appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE).

Data sources

A comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database’s inception to September 2014 was performed.

Study selection

Eligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE.

Data extraction

Reviewers working independently and in duplicate extracted data and assessed the risk of bias.

Data synthesis

We identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random-effects models to pool results across studies, the cure rate was 98 % (95 % CI 97–98 %, I ² = 10 %) with BNE and 97 % (95 % CI 96–98 %, I ² = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10–17 % I ² = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6–3.1 %, I ² = 87 %) with MIP (P < 0.001). There was a statistically significant lower risk of laryngeal nerve injury with MIP (0.3 %) than with BNE (0.9 %), but similar risk of infection (0.5 vs. 0.5 %) and mortality (0.1 vs. 0.5 %).

Limitations

The available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency for some outcomes (cure rate, hypocalcemia).

Conclusion

MIP and BNE are both effective surgical techniques for the treatment of primary hyperparathyroidism. The safety profile of MIP appears superior to BNE (lower rate of hypocalcemia and recurrent laryngeal nerve injury).

     

Tumor Proximity to the Recurrent Laryngeal Nerve in Patients with Primary Hyperparathyroidism Undergoing Parathyroidectomy

Background

Recurrent laryngeal nerve (RLN) injury is a rare complication for patients undergoing neck exploration for primary hyperparathyroidism (pHPT). Distances between RLNs and parathyroid adenomas have not been previously published. In this study we used a RLN monitor to identify the RLN and to measure the proximity to parathyroid tumors.

Methods

Patients with pHPT (n?=?136) underwent neck exploration and had the clinical data recorded prospectively. Adenomas were recorded in 1 of 4 locations (right upper, right lower, left upper, left lower). Measurement of RLN to adenoma distances were recorded intraoperatively with the gland in situ. The RLN location was confirmed with a RLN monitor.

Results

The average RLN to adenoma distance was 0.52?±?0.52?cm. Adenomas in the right upper position were significantly closer to the nerve (0.25?±?0.39?cm) compared with adenomas in the left upper (0.48?±?0.61?cm, p?=?.03), left lower (0.70?±?0.53?cm, p?<?.001), and right lower position (1.02?±?0.56?cm, p?<?.001). Left upper adenomas were also significantly closer to the nerve compared with right lower adenomas (p?<?.001). Adenomas in the right upper position abutted the nerve more often (47?%) compared with adenomas in other positions (p?=?.001). There were no perioperative characteristics that predicted tumor abutment. There were no permanent RLN injuries.

Conclusion

In patients with sporadic pHPT, parathyroid adenomas in the right upper location have, on average, greater proximity to the RLN and are more often directly abutting compared with adenomas in other locations.     

Long-term Outcome after Parathyroidectomy in Patients with Advanced Primary Hyperparathyroidism and Associated Vitamin D Deficiency

Introduction Primary hyperparathyroidism (PHPT) is increasingly being recognized in the developing world, but long-term recovery of affected organs after successful parathyroidectomy, remains unaddressed. A study was therefore undertaken to elucidate this aspect of care among our patients. Methods Retrospective analysis was done on 82 PHPT patients who underwent parathyroidectomy between 1991 and 2004. Appropriate biochemical and radiological investigations revealed the recovery pattern in target organs. Results Follow-up ranged between 2 years and 13 years. Bone pain and muscle weakness disappeared quickly in all patients. Radiographs revealed vigorous but disorderly remineralization in lesions that healed within a median period of 3 months. Mean 25-OH vitamin D levels in the preoperative and postoperative period were 11.6 ± 8.7 and 16.94 ± 12.77 ng/ml, respectively. Twenty-four of 32 (75%) patients remained persistently vitamin D deficient (mean level 12.15 ± 5.45 ng/ml) postoperatively and in the long term (2–13 years; median: 3 years). Kidney disease occurred in 43 patients, and 74% of them became symptom free; in 9 patients it remained static and in 3 others it progressed to end-stage renal disease (ESRD). Seven patients had pancreatitis, 5 became symptom free, and 2 had no relief after failed exploration (n = 1) and recurrence (n = 1). Overall recurrence and persistence rates were 2.7% each. Of the 5 deaths in the follow-up period, three were due to ESRD and one was due to cerebral metastasis. Conclusions In India, PHPT presents at an advanced stage and is associated with vitamin D deficiency. Persistent vitamin D deficiency after operation delays bone recovery. Replenishment of vitamin D stores in the follow-up has to be continuously ensured. Recovery from renal disease is gradual and may never occur in some patients; in others, it may progress to ESRD. Patients recover fully from pancreatitis.     

Predictors of Bone Mineral Density Improvement in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism

Introduction

Primary hyperparathyroidism (PHPT) results in increased bone turnover, resulting in bone mineral density (BMD) reduction and a predisposition towards fractures. Parathyroidectomy (PTX) is the only definitive cure.

Objective

The primary goals of this study were to investigate the impact of PTX on BMD in patients with PHPT and to identify factors associated with post-operative BMD improvement using a multivariate model.

Methods

Between 1999 and 2010, a total of 757 patients underwent PTX for treatment of PHPT; 123 patients had both a pre- and a post-operative dual-energy X-ray absorptiometry (DEXA) scan. A prospective database was queried to obtain information about patient demographics, medications, comorbidities, and pre- and post-operative laboratory values. A Cox regression model was used to stratify patients and to identify factors that independently predict BMD response following PTX in this patient population.

Results

Overall, mean percent change in BMD was +12.31 % at the spine, +8.9 % at the femoral neck (FN), and +8.5 % at the hip, with a mean follow-up of 2.3 ± 1.5 years. A total of 101 (82.1 %) patients had BMD improvement at their worst pre-operative site. In patients who improved, 69.9 % (n = 86) had >5 % increase. Factors associated with BMD improvement at the worst pre-operative site were as follows: male gender (hazard ratio [HR] 2.29; 95 % confidence interval [CI] 1.54–4.21); pre-operative BMD with T-score less than ?2.0 (HR 1.89; 95 % CI 1.11–2.39); age <55 years (HR 1.74; 95 % CI 1.14–2.25); BMD DEXA scan at >2.5 years post-operatively (HR 1.71; 95 % CI 1.09–2.17); history of previous fracture (HR 1.24; 95 % CI 1.05–1.92); and private insurance (HR 1.18; 95 % CI 1.06–2.1). The use of bisphosphonates, estrogens, vitamin D supplementation, or tobacco; obesity; history of previous PTX, serum calcium or parathyroid hormone levels were not independently associated with post-operative BMD improvement.

Conclusion

Osteoporosis is one of the established National Institutes of Health criteria for PTX in asymptomatic patients with PHPT, but BMD improvement is not consistently seen during the post-operative period. Gender, age, more severe pre-operative bone disease, and insurance status were all predictors for greater BMD improvement following PTX. Further studies with a rigorous post-operative BMD regimen are needed in order to validate these results.     

Primary Hyperparathyroidism: An Analysis of Failure of Parathyroidectomy

Background

Preoperative imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT) is used primarily to facilitate targeted parathyroidectomy. Failure of preoperative localisation mandates a bilateral exploration. It is thought that the results of imaging may also predict the success of surgery. The aims of this study were to assess whether the findings on preoperative localisation influenced outcomes following parathyroidectomy for PHPT and to explore factors underlying failure to cure at surgery.

Methods

We analysed outcomes of all patients who underwent first-time surgery for PHPT in two centres over a 5-year period to determine an association with demographic characteristics and findings on preoperative imaging. Records of patients not cured by initial surgery were reviewed to explore factors underlying failure to cure.

Results

The failure rate (persistent disease) in the entire cohort was 5 % (25/541) (bilateral neck explorations, 5 %; unilateral exploration, 7 %; targeted approach, 4 %), while two patients developed recurrent disease. In patients who had undergone dual imaging with an ultrasound scan and ^99mTc-sestamibi scintigraphy, failure rates with “lateralised and concordant” imaging, “nonconcordant” imaging, and “dual-negative” imaging were 2, 9, and 11 %, respectively (p = 0.01). Of the 25 patients with persistent disease, multigland disease (MGD) was present in 52 % (13/25) and ectopic adenoma in 24 % (6/12).

Conclusions

Patients with PHPT who do not have lateralised and concordant dual imaging are at higher risk of persistent disease. A significant proportion of failures are due to the inability to recognise the presence and/or extent of MGD.     

甲状旁腺切除术治疗尿毒症并难治性继发性甲状旁腺机能亢进症

为了观察甲状旁腺切除部分自体移植术治疗尿毒症并难治性甲状旁腺机能亢进症的近远期疗效，定期观测了１２例严重的尿毒症性继发性甲状旁腺机能亢进且采取了甲状旁腺切除部分自体移植术的患者术前及术后第１周、第３，６，１２月其血钙磷代谢，骨Ｘ线及心／胸比值等各项指标。结果显示：①术后各时点血清磷，ＡＫＰ和甲状旁腺素水平明显下降（Ｐ＜０．０５），血清钙虽有所下降，但无统计学意义（Ｐ＞０．０５）；②骨痛及皮肤瘙痒等症状缓解率达９１．６７％；③骨吸收好转率为６６．６７％，术后心／胸比值有所下降，但无统计学意义（Ｐ＞０．０５）；④术前，术后红细胞压积无改变（Ｐ＞０．０５）。结论：甲状旁腺切除部分自体移植术是治疗尿毒症性难治继发性甲状旁腺机能亢进症的有效而可靠的方法     

Survival after Parathyroidectomy in Patients with End-stage Renal Disease and Severe Hyperparathyroidism

Background Patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism (SHPT) are at high risk of mortality. Whether an increased risk of death persists after a parathyroidectomy (PTX) is not clearly established. Subjects and methods The survival of 40 patients with ESRD and SHPT who underwent PTX was compared with that of 664 ESRD patients. Results From first dialysis, a lower mortality rate was found in the group of patients who underwent PTX than in the nonoperated ESRD group (hazard ratio: 0.23; 95% CI: 0.14–0.37). The patients who underwent PTX were younger, had a longer time on dialysis, and had a higher prevalence of kidney transplantation. The mean number of comorbidities was lower (Charlson score 4.2 ± 2.1 versus 6.4 ± 2.9, p < 0.001). Then, we randomly selected two matched controls for each PTX case (80 controls, 40 PTX) who had at least an equivalent mean duration of dialysis between the first dialysis and PTX of the PTX group. In a univariate model, there was a trend for PTX being associated with prolonged survival. The mortality was higher both among those at an advanced age and those with a high Charlson score. Adjustments for these covariates made the effect of PTX no more significant. Conclusions The risk of death of patients with severe SHPT leading to PTX differed from that of nonoperated subjects. The apparent differences in survival may be related to the number and severity of associated comorbidities. ESRD patients who undergo PTX may represent a subset of healthier subjects.     

Bone Mineral Density in Menopausal Women with Primary Hyperparathyroidism before and after Parathyroidectomy

The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has not been definitely established because both diseases occur predominantly in postmenopausal women, and because PTH has a paradoxical effect on bone. We have investigated the prevalence of reduced bone mineral density (BMD) in women with pHPT, its relationship with metabolic parameters, and its course after parathyroidectomy. A prospective observational study was carried out on perimenopausal and postmenopausal women consecutively diagnosed and operated on for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P, vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were included with a mean age of 61 ± 12 years. The prevalence of reduced BMD ( 1SD, T-score) was 80%–100% depending on site. Parathyroid hormone was higher in patients with osteoporosis (319 ± 181 pg/ml) than in those with osteopenia (230 ± 83 pg/ml) or normal BMD (148 ± 81 pg/ml; p < 0,04). Twenty-eight patients were investigated 1 year after parathyroidectomy. The BMD improved significantly at all sites, particularly in patients with osteoporosis. Age correlated inversely with BMD increases at the femoral sites (r= –0,47; p = 0,02) but not at the LS. 25-OHD₃ plasma levels correlated inversely with BMD increases at PF (r= –0,76; p < 0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic variables had a definite influence on BMD values but a tendency was observed for lower BMD in severe pHPT. One year after parathyroidectomy, there were significant BMD increases that were more marked at femoral sites, in younger patients, in patients with preoperative osteoporosis, and in those with lower plasma levels of 25-OHD₃.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Short- and Long-Term Changes in Bone Mineral Density of the Lumbar Spine After Parathyroidectomy in Patients with Primary Hyperparathyroidism

The aims of this study were (1) to analyze whether correlations exist between lumbar spine (LS) bone mineral density (BMD) and the main preoperative biochemical parameters in a large population of patients with primary hyperparathyroidism (HPT); and (2) to evaluate the LS-BMD changes after parathyroidectomy (PTx) at long-term follow-up. Sixty-two patients (median age 57 years, range 23–82 years) with confirmed primary HPT underwent LS osteodensitometry by dual-energy X-ray absorptiometry with BMD measurements at the L2–L4 region before surgery and at 1 year and 2 years after successful PTx. Three groups of patients were considered: Group A (men, n = 14, 22.6%), Group B (premenopausal women, n = 12, 19.3%), and Group C (postmenopausal women, n = 36, 58.1%). There were no linear correlations (P = NS) among the main biochemical parameters, the age of the patients, and their baseline LS-BMD values that were significantly (P < 0.01) lower in Group C patients. At 2-year follow-up the LS-BMD improved by 13.0%, 11.5%, and 11.7% in Groups A, B, and C, respectively (P = NS). In order to compare groups with the same linear relationship between age and LS-BMD, a subgroup of postmenopausal patients aged 60 years (Group C2) was considered. ANOVA showed that the improvement of the LS-BMD at l- and 2-year follow-up was higher (P = 0.002) in Group B than in Group C2 patients. The result was confirmed by using the Mann-Whitney U-test (P = 0.0078). Improvement of LS-BMD after successful PTx was significantly (P < 0.01) higher in premenopausal women, suggesting a possible role of estrogen hormone in complete bone remodeling. This study was presented at the XXVII European Symposium on Calcified Tissue, Tampere, Finland, 6–19 May, 2000     

Long-Term Symptom Relief from Primary Hyperparathyroidism Following Minimally Invasive Parathyroidectomy

Background  

The affect of the surgical approach for primary hyperparathyroidism (1HPT) on long-term symptom relief has not been studied. This study compares the long-term relief of symptoms assessed by the Parathyroidectomy Assessment of Symptoms (PAS) score in patients undergoing bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP).     

The Influence of Parathyroidectomy on Restless Legs Syndrome in Patients with Renal Hyperparathyroidism

Background

Restless legs syndrome (RLS) is a common and poorly understood movement disorder that leads to unpleasant leg sensations. Although RLS can be idiopathic, secondary etiologies such as iron deficiency and renal failure are common. The aim of this prospective cohort study was to evaluate whether RLS is a common feature in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) and if RLS-related symptoms can be influenced by surgery.

Methods

After providing written consent, patients who underwent a parathyroidectomy for rHPT between January and November 2011 answered a validated RLS-screening-questionnaire (RLSSQ). If this was suggestive for RLS a confirming questionnaire (IRLS) was also completed on the day before surgery, on the fifth postoperative day, and again during follow-up (minimum 12 months). Perioperative parathyroid hormone and calcium levels, as well as the scores of the questionnaires were analyzed.

Results

Twenty-one patients (14 men, 7 women) with a mean age of 47.8 ± 3.2 years underwent total parathyroidectomy with bilateral cervical thymectomy and parathyroid autotransplantation for rHPT. The mean score of the RLSSQ of all 21 patients prior to operation was 6.1 ± 0.5. In 10 of 21 patients (47.6 %) the results of the RLSSQ were suggestive for RLS with a mean score of 8.0 ± 0.3. The consecutive scores of the IRLS in these latter patients significantly dropped from 26.6 ± 1.4 to 19.0 ± 2.2 between the preoperative and postoperative settings (p < 0.05). After a mean follow-up of 17.3 ± 3.7 months the mean scores of the RLSSQ and the IRLS were 6.1 ± 0.6 and 16.3 ± 1.8.

Conclusions

rHPT may play a major role in the severity of RLS-associated symptoms in patients with renal failure. Consequently, parathyroidectomy may prove to be a valuable tool to reduce RLS-associated morbidity in affected patients. However, larger prospective trials are required to confirm the possible relation between RLS and rHPT seen in the present study.     

A Prospective Comparative Study Between Targeted Parathyroidectomy Under Local Anaesthesia And Conventional Parathyroidectomy In Primary Hyperparathyroidism

Introduction: Minimal invasive parathyroidectomy (MIP) has evolved as a popular method in the treatment of primary hyperparathyroidism. Our study aimed to examine how effective is MIP compared to conventional parathyroidectomy. Methods: All patients with primary hyperparathyroidism received a triage ultrasound scan. In patients who had their parathyroid glands localized by the ultrasound, parathyroidectomy was performed under local anaesthesia (LA‐MIP) via a 3‐cm incision using the lateral approach. In patients with negative imaging, they underwent conventional parathyroidectomy under general anaesthesia (GA). Cure is defined as remaining normocalcemic on follow up. The cure rate, complication rate, hospital stay and number of frozen sections utilized were compared. Results: Forty‐four patients were treated by LA‐MIP and 37 patients were treated by GA since 1999–2003. The positive predictive value of USG localization was 97%. After a median follow up of 24 months, there were no difference in the cure rate (41/44 in LA‐MIP versus 35/37 in GA, P > 0.05) and complication rate (2/44 in LA‐MIP vs 2/37 in GA, P > 0.05). However, the LA group was found to have shorter hosptial stay (median = 1 vs 2 in GA, P < 0.05) and utilized less frozen‐sections (median = 1 vs 2 in GA, P < 0.05). Conclusions: Ultrasound‐guided minimal invasive parathyroidectomy under local anaesthesia is as effective as conventional parathyroidectomy in the treatment of primary hyperparathyroidism. An estimated cost‐reduction of HK $14 432 was found in each case treated by LA‐MIP through utilizing less frozen‐sections, less general anaesthesia and shorter hosiptal stay.