Long-term Follow-up of Patients with Elevated PTH Levels following Successful Exploration for Primary Hyperparathyroidism

Several studies have documented elevated parathyroid hormone (PTH) levels after seemingly successful exploration for primary hyperparathyroidism (pHPT). It is not known if this is a transient phenomenon after pHPT surgery or if it predisposes to recurrent disease. A series of 99 consecutive patients with pHPT who had solitary parathyroid adenomas were followed for 5 years. Serum levels of PTH and biochemical variables reflecting PTH activity were measured before operation, at 8 weeks postoperatively, and then yearly for 5 years. All patients were normocalcemic after exploration. At 8 weeks after operation 28% of the patients had elevated serum PTH levels; at 5 years this figure decreased to 16%. During the 5-year follow-up one group of patients normalized their PTH levels, another groups PTH levels fluctuated, and still another group had consistently normal PTH levels. Patients with fluctuating PTH levels had increased levels of serum calcium and phosphate. Some of these patients (15%) showed signs of impaired renal function. Two patients with consistently elevated PTH levels showed signs of mild renal dysfunction, and one of them developed recurrent HPT. Elevated PTH levels after successful parathyroid surgery is not a transient phenomenon. An increased risk for recurrent disease is postulated for some of the patients who do not normalize their PTH levels postoperatively, and long-term surveillance of these patients is suggested.     

Parathyroidectomy Decreases Insulin Resistance Index in Patients with Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) has been considered a cause of insulin resistance (IR) and impaired glucose metabolism. However, there are conflicting results related with the recovery of insulin resistance in patients with PHPT following curative parathyroidectomy. Our aim is to evaluate the effects of curative parathyroidectomy on IR in patients with PHPT. This is a prospective interventional study. Twenty-one consecutive patients with symptomatic PHPT were included into the study. All patients underwent parathyroidectomy. Fasting serum glucose, calcium, phosphorous, parathormone, plasma insulin, and vitamin D levels were measured both at baseline and 2 months after parathyroidectomy. Insulin resistance was calculated by homeostasis of model assessment-insulin resistance (HOMA-IR). Two months after curative parathyroidectomy, serum levels of calcium (p?=?0.001), PTH (p?<?0.001), insulin (p?=?0.003), and HOMA-IR (p?=?0.003) decreased, while phosphorous levels increased (p?=?0.001). During this period, no changes were observed at vitamin D and glucose levels. We concluded that curative parathyroidectomy decreases HOMA-IR index in patients with PHPT. Studies with larger population and longer follow-up period are required to confirm our results.     

Morbidity Associated with Concomitant Thyroid Surgery in Patients with Primary Hyperparathyroidism

Annals of Surgical Oncology - Recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism are serious complications in thyroid and parathyroid surgery. The extent to which incidentally detected...     

Intraoperative Parathyroid Hormone Monitoring in Patients with Recognized Multiglandular Primary Hyperparathyroidism

Background  

Intraoperative parathyroid hormone (IOPTH) monitoring reliably predicts cure of primary hyperparathyroidism (PHPT) due to single-gland disease. However, its utility in PHPT caused by multiple-gland disease (MGD) is still debated, for both detection and prediction of adequate resection. Our hypothesis is that once MGD is encountered during an operation, more stringent criteria for determining adequate resection can improve cure rates.     

Disparities in Time to Surgeon Evaluation Among Patients with Primary Hyperparathyroidism

BackgroundA majority of patients with primary hyperparathyroidism are not referred for surgical evaluation. We hypothesized that disparities in the rate of surgeon evaluation by language, race and ethnicity, and insurance contribute to this deficit.MethodsWe queried our institutional electronic health record registry for patients with first-incident hypercalcemia between 2010 and 2018 and subsequent biochemical diagnosis of primary hyperparathyroidism. We used the Kaplan-Meier method and Cox proportional hazards modeling to investigate estimated time to surgeon evaluation by language, race and ethnicity, and insurance status.ResultsOf 1,333 patients with a diagnosis of primary hyperparathyroidism, 74% were female, 67% were White, 44% were privately insured, and 88% preferred English. Fewer than one third (n = 377; 28%) were evaluated by a surgeon. After adjusting for demographic and clinical factors, Asian (hazard ratio = 0.38; 95% confidence interval, 0.18–0.84; P = .016) and Black or African American patients (hazard ratio = 0.59; 95% confidence interval, 0.39–0.90; P = .014) had a lower rate of surgeon evaluation compared to White patients. Although patients with Medicaid had a lower rate of surgeon evaluation compared to privately insured patients (hazard ratio = 0.52; 95% confidence interval, 0.35–0.77; P = .001), there was no difference in rate for those with Medicare or who were uninsured. Patients with non-English and non-Spanish language had a lower rate of evaluation compared to those who preferred English (hazard ratio = 0.47; 95% confidence interval, 0.23–0.98; P = .043).ConclusionRates of surgeon evaluation vary by race and ethnicity, insurance status, and preferred language. Evaluation of factors contributing to these disparities is needed to improve access to surgeon referral.     

Biochemical Effects from Treatment with Bisphosphonate and Surgery in Patients with Primary Hyperparathyroidism

Patients with primary hyperparathyroidism (pHPT) are sometimes treated with bisphosphonates (BPs) as an alternative to surgery despite sparse documentation of the efficacy in this disorder. It is therefore of interest to study the biochemical effects from BPs in patients with pHPT. A series of 21 pHPT patients with serum calcium levels > 2.8 mmol/L were included. One month before surgery the patients underwent intravenous infusions of 30 to 40 mg pamidronate. Study parameters were total and ionized serum calcium, intact parathormone (PTH), alkaline phosphatase (ALP) and isoenzymes, creatinine, osteocalcin, 25-OH vitamin D₃, 1,25-OH₂ vitamin D₃, urine calcium/creatinine, and osmolality. Registration of hypercalcemia-related symptoms were done by questionnaire. After pamidronate there was a temporary reduction in serum calcium with a nadir at 6 to 10 days. Normalization of serum calcium was achieved only by surgery. Intact PTH rose after pamidronate, with a maximum on day 6. Urinary calcium excretion was reduced after both pamidronate and surgery. ALP was reduced 30 days after pamidronate and also after surgery. Serum osteocalcin was not influenced by pamidronate. No statistically significant differences in symptoms were reported after treatment. In conclusion, there was a short, limited calcium-lowering effect from pamidronate in pHPT patients and a transient increase in PTH corresponding to the reduced calcium concentration. An obvious change in bone markers was found only after surgery. Treatment with BPs should not be considered an alternative to surgery, which is still the only method to cure patients with pHPT.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden June 14–17, 2004.     

Inframanubrial Parathyroid Glands in Patients with Primary Hyperparathyroidism: Alternatives to Sternotomy

Deep inframanubrial parathyroid tumors have traditionally been excised through a median sternotomy. With the advent of minimally invasive surgical access, we chose to examine the treatment options and outcomes of patients with inframanubrial mediastinal parathyroid tumors. Patients with primary hyperparathyroidism seen at a university medical center over a 12-year period were retrospectively reviewed. The utility of localization studies, methods of treatment, complications, and outcomes were examined in patients with a parathyroid tumor located in the mediastinum inferior to the manubrium. Patients with parathyroid adenomas located at the thoracic inlet were excluded. Sixteen patients with inframanubrial mediastinal tumors were treated during the study period. Altogether, 81% of the patients had undergone at least one prior neck exploration for primary hyperparathyroidism. Preoperative calcium and parathyroid hormone levels were 12.4 ± 0.36 mg/dl and 273 ± 70 pg/ml, respectively. Localization studies identified mediastinal parathyroid adenomas in the following locations: anterior mediastinum (n = 8), middle mediastinum (n = 7), posterior mediastinum (n = 1). Mediastinal computed tomography and technetium-sestamibi scans demonstrated the best sensitivity, 92% and 85%, respectively. Seven patients underwent successful excision of the mediastinal adenoma by transcervical mediastinal exploration with the Cooper retractor. The other patients underwent angiographic ablation (n = 4), anterior mediastinotomy (n = 3), video-assisted thoracoscopy (VATS) (n = 1), and VATS plus thoracotomy (n = 1). The mean hospital stay for the study group was 2.9 ± 0.7 days. The complication rate was 25%. All patients were normocalcemic after a mean follow-up of 15 ± 7 months. Most inframanubrial mediastinal parathyroid tumors can be successfully managed without median sternotomy.     

Long-Term Effects of Neridronate and its Discontinuation in Patients with Primary Hyperparathyroidism

In patients with primary hyperparathyroidism (PHPT) not suitable for surgical correction, a skeletal protection with bisphosphonates is considered a reasonable option, but the long-term effects after treatment discontinuation are not well known. Sixty postmenopausal women with PHPT were given 400–600 IU vitamin D₃ daily and 100 mg neridronate IV every 2 months for 2 years with 2 additional years of follow-up without antiresorptive therapies. Bone mineral density (BMD) progressively rose by 6.7 ± 7.6% (SD) and by 2.9 ± 4.5% at the spine and femoral neck, respectively. During follow-up, mean BMD progressively fell, but after 2 years it was still 3.9 ± 5.5% higher than baseline values at the spine. Bone alkaline phosphatase and serum C-telopeptide of type I collagen decreased significantly within 6 months (28 and 49% versus baseline, respectively) and rose to baseline values within 6–12 months during follow-up. Serum PTH significantly rose from baseline during treatment, but it remained significantly higher than baseline during follow-up. The PTH changes were significantly correlated with serum 25-hydroxyvitamin D (25OHD) levels. In conclusion, in this study we observed that in patients with mild PHPT treatment with bisphosphonates is associated with the expected changes in bone-turnover markers and that the significant increases of both hip and spine BMD are partially maintained for at least 2 years after treatment discontinuation at the vertebral site. The marked increases in serum PTH levels, particularly in subjects with low 25OHD levels, persist after treatment discontinuation and this raises the suspicion that this might reflect a worsening of PHPT.     

Osteoprotegerin Levels in Primary Hyperparathyroidism: Effect of Parathyroidectomy and Association with Bone Metabolism

The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) remains controversial. Most in vitro studies indicate that PTH decreases OPG secretion by the osteoblast, but in vivo observations are conflicting. In primary hyperparathyroidism (PHPT), hypersecretion of PTH leads to enhanced bone resorption and formation with increased risk of fracture. Patients with PHPT are cured by surgery, resulting in normalization of PTH levels and bone metabolism, but the concomitant effects on OPG production are not known. The hypothesis of the present study was that the circulating level of OPG is diminished in patients with PHPT and increases with successful parathyroidectomy. We also speculated that serum OPG may determine the magnitude of bone loss up to the time of surgery. In the present study, 20 patients (17 women and 3 men, mean age 62 y) with PHPT who were candidates for surgical cure were examined before and 12 months after surgery. Bone turnover markers decreased and BMD increased significantly after surgery. Serum OPG did not correlate with PTH before surgery (r = 0.07, P = 0.77) and was not affected by parathyroidectomy (P = 0.79). After normalization of PTH, bone formation markers showed significant (P1NP) and near-significant (osteocalcin) correlations with serum OPG. In conclusion, serum OPG is not decreased in patients with PHPT, nor is serum OPG to any demonstrable extent regulated by PTH pre- or postoperatively.     

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.     

136例原发性甲状旁腺功能亢进的诊治体会

目的分析原发性甲状旁腺功能亢进症的临床特点、诊断和治疗方法。方法回顾性分析四川大学华西医院2004年1月至2012年12月期间初次手术治疗且资料完整的原发性甲状旁腺功能亢进患者的临床资料。结果136例甲状旁腺功能亢进患者中骨型52例（38,23％）,肾型17例（12．50％）,骨。肾型7例（5．15％）,生化型24例（17．65％）,合并其他临床表现者36例（26．47％）。术前甲状旁腺激素（parathyroid hormone,PTH）值为（106．20±88．88）pmol／L（6．91～390pmol／L）,血钙值为（3．12±0．66）mmol／L（2．15～5．77mmol／L）。甲状腺及颈部淋巴结彩超和锝．甲氧基异丁基异腈放射性核素双时相显像（99Tcm-MIBI）定位诊断与手术发现符合率分别为75．00％及85．29％,联合CT检查三者符合率为86．76％。术后病理诊断：良性病变129例（94．85％）,甲状旁腺癌7例（5．15％）。良性病变中甲状旁腺腺瘤119例（92．25％）,其中单发114例（95．80％）,多发腺瘤或甲状旁腺瘤合并甲状旁腺增生5例（4．20％）;甲状旁腺增生10例（7．75％）,其中8例为甲状旁腺不典型增生或增生活跃。124例（91．18％）患者术后3d内PTH降至正常上限以下。124例（91．18％）获随访,随访时间6～112个月,中位随访时间49个月;12例（8．82％）失访。术后6个月有2例（1．47％）甲状旁腺癌患者肿瘤复发,其余病例无复发。3例（2．21％）甲状旁腺癌患者分别于术后18,19及23个月死亡,其中2例死于甲状旁腺癌全身转移,1例死于心血管意外。结论原发性甲状旁腺功能亢进的临床表现多样,手术是治疗原发性甲状旁腺功能亢进的有效手段。     

A Meta-analysis of Preoperative Localization Techniques for Patients with Primary Hyperparathyroidism

Background  

Reported accuracy of preoperative localization imaging for primary hyperparathyroidism (pHPT) varies. The purpose of this study is to determine the accuracy of ultrasound, sestamibi-single photon emission computed tomography (SPECT), and four-dimensional computed tomography (4D-CT) as preoperative localization strategies.     

Primary Hyperparathyroidism

The cases of 60 patients who underwent parathyroidectomy are described. Past, present and future aspects of the diagnosis of hyperparathyroidism, are discussed. In several patients in the series renal calculi had been present for over 20 years before the diagnosis was made. The reasons for this delay are considered.     

Management of Skeletal Health in Patients With Asymptomatic Primary Hyperparathyroidism

Asymptomatic primary hyperparathyroidism (PHPT) may cause adverse skeletal effects that include high bone remodeling, reduced bone mineral density (BMD), and increased fracture risk. Parathyroid surgery, the definitive treatment for PHPT, has been shown to increase BMD and appears to reduce fracture risk. Current guidelines recommend parathyroid surgery for patients with symptomatic PHPT or asymptomatic PHPT with serum calcium >1 mg/dL above the upper limit of normal, calculated creatinine clearance <60 mL/min, osteoporosis, previous fracture, or age <50 yr. The type of operation performed (parathyroid exploration or minimally invasive procedure) and localizing studies to identify the abnormal parathyroid glands preoperatively should be individualized according to the skills of the surgeon and the resources of the institution. In patients who choose not to be treated surgically or who have contraindications for surgery, medical therapy should include a daily calcium intake of at least 1200 mg and maintenance of serum 25-hydroxyvitamin D levels of at least 20 ng/mL (50 nmol/L). Bisphosphonates and estrogens have been shown to provide skeletal benefits that appear to be similar to parathyroid surgery. Cinacalcet reduces serum calcium in PHPT patients with intractable hypercalcemia but has not been shown to improve BMD. It is not known whether any medical intervention reduces fracture risk in patients with PHPT. There are insufficient data on the natural history and treatment of normocalcemic PHPT to make recommendations for management of this disorder.     

Impact of Intraoperative Parathyroid Hormone Levels on Surgical Results in Patients with Renal Hyperparathyroidism

The aim of our study was to evaluate the impact of intraoperative parathyroid hormone (PTH) measurement on surgical results in patients with renal hyperparathyroidism (HPT). From December 1999 to February 2004, a series of 95 consecutive patients underwent total parathyroidectomy and intraoperative PTH measurement for renal HPT. Intraoperative PTH was measured before and 15 minutes after parathyroidectomy with the Immulite DPC assay for intact PTH. The median PTH levels before surgery were 133.0 pmol/L, which declined to 5.9 pmol/L at the end of the operation. At follow-up, 91 of 95 (96%) patients presented with normal calcium levels. Persistent renal HPT was seen in three patients, and recurrent HPT was diagnosed in another. In 99% of the patients the intraoperative PTH levels declined more than 50% and in 73% the PTH decay was more than 90%. In 64% of the patients PTH levels dropped into the normal range (< 7.6 pmol/L). Altogether, 97% of the patients with an intraoperative PTH decrease of more than 90% presented with normal PTH levels postoperatively (p = 0.0237), as did all of the patients whose intraoperative PTH dropped into the normal range (p = 0.0432). Intraoperative PTH measurement with a decrease in intraoperative PTH of at least 90% is highly predictive of successful parathyroidectomy and normalization of postoperative calcium and PTH levels.     

Development of a Formula to Predict Parathyroid Carcinoma in Patients with Primary Hyperparathyroidism

Background

Cure of parathyroid carcinoma (PC) requires initial en bloc resection, including resection of all tumor-bearing tissue, with hemithyroidectomy and dissection of the central lymph node compartment. Unfortunately, no reliable preoperative criteria have yet been assessed to indicate a high likelihood of PC. Thus, the aim of the present study was to develop a formula to indicate preoperatively the presence of PC.

Methods

A prospective database of 1,363 patients with primary hyperparathyroidism (pHPT) was screened for patients with PC. Age, gender, surgical procedures, laboratory data, and follow-up results were evaluated and compared to a group of patients with benign pHPT. Based on preoperative serum calcium (Ca) and parathyroid hormone (PTH) levels, as well as patients’ age at the time of diagnosis, a formula was developed by a multivariate logistic model that estimates the individual risk for PC.

Results

Between 1987 and 2008, 19 patients with PC were identified. Ca (3.8?±?0.3 vs 2.9?±?0.3 mmo/l; p?=?0.0002) and PTH levels (1,250?±?769 vs 194?±?204?pg/ml; p?=?0.0030) were significantly higher in patients with PC than in those with benign pHPT. Patients with PC were also significantly younger than patients with benign pHPT (48.9?±?12.1 vs 59.1?±?13.8?years; p?<?0.05). With a ≥5?% probability that a given patient suffered from PC, the sensitivity and specificity to identify the disease were 100 and 30?%, respectively, with the new Ca, PTH, and age based logarithmic formula.

Conclusions

The new logarithmic formula can be used to calculate the individual risk for PC. If the calculated individual risk exceeds 5?%, en bloc resection seems to be justified to provide long-term cure in case of PC.     

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.     

Video-Assisted Bilateral Neck Exploration in Patients with Primary Hyperparathyroidism and Failed Localization Studies

Background  

In primary hyperparathyroidism (pHPT) positive preoperative localization studies are accepted as a precondition for applying minimally invasive surgical techniques. Without localization, open bilateral neck exploration (BNE) is considered the standard option. Thepresent study analyzes the feasibility and effectiveness of minimally invasive video-assisted BNE in patients with pHPT and negative or discordant localization studies.