Effects of Smoking on Severity of Disease in Primary Hyperparathyroidism

In healthy subjects, smoking is associated with lower plasma levels of parathyroid hormone (PTH) and decreased bone mineral density (BMD). The effect of smoking on PTH, skeletal metabolism, and size/histology of the parathyroid glands in primary hyperparathyroidism (PHPT) is unknown. We investigated, in a cross-sectional study, whether smoking affects PTH levels, BMD, and weight/histology of removed parathyroid tissue in PHPT. We studied 344 (285 women) parathyroidectomized patients with PHPT (24% smokers). Biochemistry was determined at the time of diagnosis. BMD was measured before and after surgical cure. Smoking was associated with lower PTH (9.9 ± 1.8 [SD] vs. 12.2 ± 1.8 pmol/l, P < 0.01) and higher phosphate (0.95 ± 0.17 vs. 0.86 ± 0.17 mmol/l, P < 0.01) levels. Adjustments for between-group differences in age, sex, body weight, plasma creatinine, and 25-hydroxyvitamin D (25OHD) levels did not change the findings. Neither weight of removed adenomatous and hyperplastic tissue nor BMD differed according to smoking status. After adjustment for body weight, age, sex, and 25OHD levels, smokers had slightly lower BMD at the whole body but not at the spine, hip, or forearm. Independent of smoking status, surgical cure caused a significant increase in BMD at all measurement sites. In PHPT smoking is associated with lower plasma PTH and higher phosphate levels. Adjustment for confounders of PTH did not change the results. In contrast to healthy subjects, smoking seems not to decrease BMD in PHPT. Smoking may compromise the correct diagnostic evaluation of borderline hyperparathyroidism. It is unknown to what extent smoking in PHPT affects fracture risk and indication for surgery.     

Presentation, Management, and Outcomes of Hyperparathyroidism in Octogenarians and Nonagenarians

Background

Various elective surgical procedures are routinely performed on patients ≥80 years of age. With primary hyperparathyroidism (PHPT), surgical management is the only treatment. The goal of this study was to compare presentation and outcome of patients ≥80 to that of those <80 years of age.

Methods

Retrospective review of a prospectively collected database of all parathyroidectomies for PHPT performed at a university hospital. Patients ≥80 years at the time of surgery compared with patients <80 years.

Results

Over 13 years, 1,826 patients underwent parathyroidectomy for PHPT. A total of 154 patients were ≥80 years at the time of surgery (8.4 %), ranging from 80 to 91 years. Patients ≥80 years had higher serum PTH, creatinine and vitamin D levels and lower T scores. Calcium levels were similar. Patients ≥80 years had a greater history of hypertension, coronary artery disease, congestive heart failure, and stroke. Psychiatric disease was less common. Patients ≥80 years had the procedure under local anesthesia only more often. Use of a unilateral approach was equivalent. Rates of adenoma, double adenoma, and hyperplasia were comparable. Patients ≥80 years were observed overnight more frequently. Stays >24 h and disease recurrence and persistence, as well as morbidity rates, were all equivalent.

Conclusion

Disease presentation of PHPT in patients ≥80 is similar to <80. Despite increased comorbidities, parathyroidectomy is a safe procedure in this patient population with a noted equivalent complication rate to younger patients. Operative management remains the only treatment. Patient age should not be a deterrent to offer curative surgical intervention.     

Apoptosis in Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis.     

Utility of Intraoperative PTH for Primary Hyperparathyroidism Due to Multigland Disease

Background  

Surgical resection is the only curative therapy for patients with primary hyperparathyroidism (1HPT). Although cure rates of parathyroidectomy are generally high, failure is most often due to unrecognized multigland disease (MGD), which compromises 15–20% of patients with 1HPT. The use of intraoperative PTH (ioPTH) monitoring is well established for single-gland disease. Controversy remains over the utility of ioPTH in MGD, with concern for false-positive results leading to prematurely concluding the operation and leaving behind abnormal parathyroid tissue, risking future recurrence. The aim of this study was to determine the utility of ioPTH monitoring for MGD.     

Multigland Disease and Slower Decline in Intraoperative PTH Characterize Mild Primary Hyperparathyroidism

Background

Many patients with primary hyperparathyroidism (PHPT) present with less severe biochemical parameters. The purpose of this study was to compare the presentation, operative findings, and outcomes of these patients with “mild” PHPT to patients with “overt” disease.

Methods

A retrospective review of a prospectively collected parathyroid database was performed to identify cases of PHPT undergoing an initial neck operation. Patients were classified as mild when either the preoperative calcium or PTH was within the normal limits. Comparisons were made with the Student’s t test, Chi-squared test, or Wilcoxon rank-sum test where appropriate. Kaplan–Meier estimates were plotted for disease-free survival and compared by the log-rank test.

Results

Of the 1,429 patients who met inclusion criteria, 1,049 were classified as overt and 388 (27.1 %) were mild. Within the mild group, 122 (31.4 %) presented with normocalcemic PHPT and 266 (68.6 %) had a normal PTH. The two groups had similar demographics and renal function. Interestingly, the mild group had more than double the rate of kidney stones (3.1 vs. 1.3 %, p = 0.02). The mild group was less likely to localize on sestamibi scan (62.4 vs. 78.7 %, p < 0.01). Intraoperatively, more mild patients exhibited multigland disease (34.3 vs. 14.1 %, p < 0.01). When examining intraoperative PTH (IoPTH) kinetics where single adenomas were excised, the IoPTH fell at a rate of 6.9 pg/min in mild patients compared with 11.5 pg/min in the overt group (p < 0.01). Accordingly, 62.2 % of patients in the overt group and 53.3 % in the mild group were cured at 5 min postexcision (p < 0.01). There was no difference in the rates of persistence or recurrence between the groups, and disease-free survival estimates were identical (p = 0.27).

Conclusions

Patients with mild PHPT were more likely to have multigland disease and a slower decline in IoPTH, but these patients can be successfully treated with surgery.     

Epidemiology of Primary Hyperparathyroidism

Primary hyperparathyroidism is the third most common endocrine disorder. The epidemiology of this disorder is increasingly well understood, but significant limitations still exist in our understanding of the mortality, hospitalizations, incidence, prevalence, and costs associated with this condition. These limitations are due to the small number of population-based epidemiologic studies that have evaluated this condition. Further studies will be required to fully characterize the epidemiology of primary hyperparathyroidism.     

原发性甲状旁腺功能亢进症的治疗

原发性甲状旁腺功能亢进症在黄种人是少见病，国内仅几家大医院积累病例超过100例，北京协和医院自1980年到目前为止．诊治过250例。据我们的资料，85％是甲状旁腺腺瘤(其中98％是单侧腺瘤)．11％是甲状旁腺增生，4％是腺癌，这三种病变临床上均出现原发性甲状旁腺功能亢进症．治疗的惟一方法是外科手术摘除．病理不同，手术方法不同，就我们的经验，结合国外文献报道．分述如下。     

Surgery in Primary Hyperparathyroidism: Extensive Personal Experience

Parathyroidectomy is the optimal treatment for primary hyperparathyroidism (PHPT) and provides a cure in the vast majority of cases. Over the last 2 decades, improvements in preoperative localization and the development of intraoperative parathyroid hormone monitoring have opened the door for new surgical approaches to parathyroidectomy. Minimally invasive parathyroidectomy is performed under regional or local anesthesia. It requires less surgical dissection resulting in decreased trauma to tissues and is more effective and less costly than traditional bilateral cervical exploration. This article reviews our approach reflecting advances in preoperative localization, anesthetic techniques, and intraoperative management of patients undergoing parathyroidectomy for the treatment of PHPT.     

Role for Limited Neck Exploration in Young Adults with Apparently Sporadic Primary Hyperparathyroidism

BACKGROUND: The risk of multiglandular disease (MGD) dictates the extent of exploration in patients with primary hyperparathyroidism (PHPT). Historically, young patients with PHPT were more likely to have MGD, but the existing literature is sparse and conflicting. We hypothesized that young adults (ages 16-40 years) without familial PHPT have a disease process similar to that in older patients. METHODS: A 22-year retrospective chart review was performed on patients who underwent neck exploration for PHPT at our tertiary care center. Altogether, 708 charts were reviewed for demographics, family history, laboratory values, operative findings, pathology, and outcomes. RESULTS: As a group, young adults comprised 14.0% of the total population and were more likely to have preexisting familial disorders of PHPT (p < 0.01), therapeutic failure (p < 0.01), failure to identify an abnormal parathyroid at operation (p < 0.01), and higher reoperative rates (p = 0.02); they were less likely to have single-gland disease (p = 0.04). Young adults without a family history of the disease demonstrated no disease differences except for a higher rate of symptoms (p < 0.01). Additional analysis found that patients with a family history of hypercalcemia, a sole family member with PHPT, or nephrolithiasis ("possible" family history) were more likely to have MGD (relative risk 2.0). CONCLUSIONS: In this largest single-institution study of young adults with sporadic PHPT, we conclude that sporadic PHPT in young adults represents a disease entity similar to that in older patients, with no increased risk for MGD, and hence they can be managed with a similar surgical approach. Further studies are needed to assess the role of a "possible" family history as a risk factor for MGD.     

Nontraditional Manifestations of Primary Hyperparathyroidism

Classical primary hyperparathyroidism (PHPT) was previously a multisystemic symptomatic disorder not only with overt skeletal and renal complications but also with neuropsychological, cardiovascular, gastrointestinal, and rheumatic effects. The presentation of PHPT has evolved, and today most patients are asymptomatic. Osteitis fibrosa cystica is rarely seen today, and nephrolithiasis is less common. Gastrointestinal and rheumatic symptoms are not part of the clinical spectrum of modern PHPT. It remains unclear whether neuropsychological symptoms and cardiovascular disease, neither of which are currently indications for recommending parathyroidectomy (PTX), are part of the modern phenotype of PHPT. A number of observational studies suggest that mild PHPT is associated with depression, decreased quality of life, and changes in cognition, but limited data from randomized controlled trials (RCTs) have not indicated consistent benefits after surgery. The increased cardiovascular morbidity and mortality in severe PHPT has not been definitively demonstrated in mild disease, although there is some evidence for more subtle cardiovascular abnormalities, such as increased vascular stiffness, among others. Results from observational studies that have assessed the effect of PTX on cardiovascular health have been conflicting. The single RCT in this area did not demonstrate that PTX was beneficial. Despite recent progress in these areas, more data from rigorously designed studies are needed to better inform the clinical management of patients with asymptomatic PHPT.     

Surgical Management of Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a common endocrine disorder in which the inappropriate elevation in serum parathyroid hormone level results in hypercalcemia. Most cases are caused by a single adenomatous parathyroid gland and less than 15% are caused by multiglandular disease. The incidence of PHPT appears to be increasing. More patients are being identified earlier and often before symptoms develop. Parathyroidectomy is the only definitive management; with it, the patient can achieve biochemical homeostasis and symptom relief, and sequelae are prevented. Even for asymptomatic patients with PHPT, there is a growing trend to recommend early surgical intervention. Controversy continues regarding the role of and reliance on various technologies, such as preoperative localization imaging, intraoperative parathyroid hormone level measurements, and minimally invasive surgery. Although both traditional bilateral 4-gland exploration and targeted approaches are accepted surgical techniques, there is a growing trend in unilateral targeted operations often using these technologies. Regardless of surgical approach, the expected success rate is greater than 95%. This article provides an overview of the contemporary surgical management of PHPT.     

Minimally Invasive, Radioguided Surgery for Primary Hyperparathyroidism

Background: Primary hyperparathyroidism affects 1 in 700 individuals in the United States. A single adenoma is responsible in over 85% of cases. Surgery remains the most effective treatment. This study was designed to assess the feasibility of minimally invasive radioguided parathyroidectomy MIRP with confirmation of excision by ex vivo radioactivity alone.Methods: Seventy-five consecutive patients with primary hyperparathyroidism were prospectively studied. Following sestamibi scan, patients underwent unilateral neck exploration guided by a handheld gamma probe, which was also used to measure ex vivo radioactivity of excised tissue.Results: The sestamibi scan was positive in 88% of the patients. A small incision mean, 3.2 ± 0.3 cm was sufficient. Ectopic gland sites were localized in five patients with positive scans and single adenomas. Mean operative time was 48 minutes range, 15–125 minutes, with shorter procedures after the initial 20 cases mean, 24 vs. 72 minutes; P < .01. Radioguided parathyroidectomy was successful in 97%, with a mean follow-up of 11 months range, 1–26 months. As noted previously, adenomatous parathyroid glands contained more than 20% of the background radioactivity.Conclusions: MIRP is a feasible alternative to bilateral dissection with the advantages of guided dissection and rapid confirmation, and may become the procedure of choice for primary hyperparathyroidism.     

原发性甲状旁腺功能亢进症手术疗效(附32例随访)

原发性甲状旁腺功能亢进症(primaryhyperparathy鄄roidism,PHPT)是一种临床表现多样化的内分泌疾患,严重时可致病人虚弱、残废,手术治疗是主要手段。旨在了解手术后术前存在的多种临床表现,尤其骨骼系统病变是否满意。我们对1992年1月至2002年6月收治的32例经手术治疗的PHPT进行了随访,现报告如下。临床资料1.一般资料32例病人中女22例,男10例;年龄15～79岁;病程3个月至17年。2.临床表现术前主要表现为以骨痛为主的多种骨病变及高血钙症状。32例均有不同程度不同部位骨痛,以下肢及脊柱多见,12例出现步态异常,表现为跛行或摇摆步,15例多…     

Medical Management of Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in the outpatient population. It is diagnosed in most individuals in the Western world at an asymptomatic stage without signs or symptoms of parathyroid hormone (PTH) calcium excess. Nonspecific symptoms include weakness, malaise, fatigue, and possible mood disturbances, which may be present at the time of diagnosis. The diagnosis of PHPT is confirmed in the presence of hypercalcemia and a normal or elevated PTH level in the absence of conditions that mimic PHPT. Indications for surgery have recently been revised based on international consensus, and surgery is advised in the presence of significant hypercalcemia, impaired renal function, and osteoporosis and in individuals younger than 50 yr. The classical complications of PHPT are skeletal fragility, nephrolithiasis, and nephrocalcinosis. Surgery is always appropriate in an individual with confirmed PHPT after excluding conditions that can mimic PHPT and in the absence of contraindications. Individuals with asymptomatic PHPT not meeting the guidelines for surgery or those with contraindications for surgery may be followed and considered for medical management. For those at an increased risk of fragility fracture, antiresorptive therapy may be considered with close monitoring of biochemical data and bone densitometry. Targeted therapy with a calcimimetic agent may be of value in lowering serum calcium and PTH. There are currently no fracture data for the medical options available, and prospective randomized controlled trials are required to confirm the effects of medical therapy on fracture risk reduction in those with asymptomatic PHPT.