Asymptomatic Primary Hyperparathyroidism

The clinical profile of primary hyperparathyroidism (PHPT) as it is seen in the United States and most Western countries has evolved significantly over the past half century. The introduction of the multichannel serum autoanalyzer in the 1970s led to the recognition of a cohort of individuals with asymptomatic hypercalcemia, in whom evaluation led to the diagnosis of PHPT. The term “asymptomatic primary hyperparathyroidism” was introduced to describe patients who lack obvious signs and symptoms referable to either excess calcium or parathyroid hormone. Although it was expected that asymptomatic patients would eventually develop classical symptoms of PHPT, observational data suggest that most patients do not evolve over time to become overtly symptomatic. In most parts of the world, the asymptomatic phenotype of PHPT has replaced classical PHPT. This report is a selective review of data on asymptomatic PHPT: its demographic features, presentation and natural history, as well as biochemical, skeletal, neuromuscular, psychological, and cardiovascular manifestations. In addition, we will summarize available information on treatment indications and options for those with asymptomatic disease.     

Role of surgery in mild primary hyperparathyroidism in the elderly

BACKGROUND: The appropriate management of elderly patients with mild hyperparathyroidism is the subject of much debate. METHODS: A Medline literature search was conducted using the keywords 'hyperparathyroidism', 'asymptomatic' and 'elderly'. The references of the primary sources were examined for further citations. Personally collected cullings from journals and abstracts from journals were used as an additional source of data. RESULTS AND CONCLUSION: No prospective randomized controlled trial comparing parathyroidectomy with conservative management for patients with mild or asymptomatic hyperparathyroidism has been published. There are a number of longitudinal studies that attempt to characterize the natural history of hyperparathyroidism, but most do not stratify patients according to age when assessing outcome. None the less, it is clear that elderly patients present with a different spectrum of problems, particularly indistinct neuropsychiatric and musculoskeletal symptoms, and these are likely to be improved by surgery. The evidence allows the conclusion that the truly asymptomatic elderly patient can be successfully managed conservatively; there is a good prospect of benefit from surgery for those with symptomatic disease, and such patients should not be denied an operative option.     

Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey

BACKGROUND: The treatment of patients with asymptomatic primary hyperparathyroidism remains controversial despite a National Institutes of Health consensus statement. This statement also recommended a randomized clinical trial because none exists to address this issue. METHODS: Informed consent was obtained from 53 asymptomatic patients with confirmed asymptomatic primary hyperparathyroidism who participated in this randomized trial of parathyroidectomy versus observation. Patients completed the SF-36 Health Survey, an instrument that measures wellness, every 6 months for 2 years. Average annual changes were compared. RESULTS: Fifty-three patients (42 female, 11 male) with asymptomatic, mild (serum calcium level, 10.1-11.5 mg/dL) asymptomatic primary hyperparathyroidism who agreed to participate were randomized into either a surgical group or an observation group. The mean calcium level was 10.31 mg/dL. The only demographic difference between groups was age, with the operative group being older (66.7 vs 62.6 years; P <.03). The scores on 2 of the 9 domains of the SF-36 were significantly different (P <.007 and <.012, respectively); both favored the operative group. CONCLUSIONS: Improved function is seen after parathyroidectomy when compared with patients who did not undergo operation. This study supports surgical management of mild primary hyperparathyroidism at the time of diagnosis because many patients have reversible nonclassic symptoms of the disease.     

Hyperparathyroidism in the elderly.

Primary hyperparathyroidism was studied in a well-defined geriatric population of 1129 individuals during a three-month interval. Primary hyperparathyroidism was diagnosed in 1.5%. The diagnosis was based on a morphologic and biochemic basis. From clinical material consisting of 400 patients treated surgically for primary hyperparathyroidism during a ten-year period, 158 patients (38%) above the age of 64 were studied. At the preoperative evaluation, neuromuscular symptoms were present in 80%, renal insufficiency and kidney stones in each 16%, constipation and/or anorexia in 38%. Ten per cent were considered asymptomatic. In 80% the primary hyperparathyroidism was caused by a solitary adenoma. Ninety-four per cent became normocalcemic following the operation. Consistent hypocalcemia requiring vitamin-D treatment occurred in 3%, and 2% had a persisting hypercalcemia or later recurrence. The therapeutic effect on the neuromuscular symptoms, constipation, anorexia, and renal stone formation was considered good or fair in most of the cases. Primary hyperparathyroidism in the elderly occurs with a high prevalence. It can be treated successfully by surgical therapy with a low cost of morbidity, mortality, and medical care.     

Clinical symptoms of hyperparathyroidism and sizes of the parathyroid gland tumors

Three groups of patients with different degrees of primary hyperparathyroidism were compared: 36 patients with asymptomatic tumors (incidentalomas) of the parathyroid glands, 20 patients with parathyreoadenomas of medium size and mild signs of hyperparathyroidism and 26 patients with large adenomas and severe manifestations of the disease. It was shown that asymptomatic tumors of the parathyroid glands (incidentalomas) might turn into clinically marked hyperparathyroidism as the size of the parathyroid tumors was growing.     

The utility of a rapid parathyroid assay for uniglandular, multiglandular, and recurrent parathyroid disease

The rapid parathyroid hormone assay (rPTH) is an effective tool in minimally invasive resections of parathyroid adenomas. However, there are relatively few reports examining its utility in the full spectrum of parathyroid disease. The purpose of this study was to examine the utility of the rapid parathyroid hormone assay in uniglandular, multiglandular, and recurrent hyperparathyroidism. A retrospective analysis of all patients undergoing parathyroid resection from June 2001 to March 2003 was undertaken. All patients underwent preoperative localization studies. Rapid parathyroid hormone (PTH) levels were drawn immediately prior to and 10 minutes following parathyroid resection. A decline of > or = 50 per cent rPTH qualified as a successful/complete resection. Additional intraoperative samples were drawn as needed for patients with multiglandular disease. Of 46 treated patients who were examined (average age, 54 years), 30 had single, 12 patients had multigland disease, and 4 had recurrent/persistent hyperparathyroidism. Thirty-seven patients had primary hyperparathyroidism (32 with single and 3 with double adenomas; 2 with hyperplasia), 4 patients had secondary hyperparathyroidism, and 5 tertiary hyperparathyroidism. All procedures were considered successful, as every patient exhibited a postresection decrement in rPTH exceeding 50 per cent (average decrement, 91%). Although 2 patients exhibited a postoperative PTH increase exceeding 50 per cent of the preoperative value, all remained asymptomatic and eucalcemic (median follow-up, 21.5 months). The rPTH assay is an effective tool in determining success of parathyroidectomy in patients with primary uni- and multiglandular as well as recurrent hyperparathyroidism. It can be used to achieve minimally invasive neck dissections or guide surgical decision-making in more complex cases.     

Familial hypocalciuric hypercalcaemia as a differential diagnosis of hyperparathyroidism: studies in a large kindred and a review of surgical experience in the condition

We have studied 46 members of a large kindred with familial hypocalciuric hypercalcaemia (FHH) after a neck exploration failed to cure hypercalcaemia in an asymptomatic patient. Serum calcium, serum phosphate, plasma parathormone and vitamin D metabolites do not distinguish affected members from patients with hyperparathyroidism. Because of the continuing debate as to whether or not FHH is a variant of, or distinct from, hyperparathyroidism, we have carried out a review of surgical experience with subtotal parathyroidectomy in hyperparathyroidism secondary to parathyroid hyperplasia and in FHH. Whereas the procedure is successful in 90 per cent of the former cases only one case of FHH has been cured by it. This provides evidence for the two conditions being aetiologically distinct. Before patients with asymptomatic hypercalcaemia are referred for parathyroid surgery the calcium:creatinine clearance ratio should be measured using a 2 h urine sample collected after an overnight fast and a fasting blood sample. If this ratio is less than 0.01 then screening of first degree relations should be undertaken before any parathyroid surgery is performed. Unnecessary surgery can therefore be avoided.     

Asymptomatic primary hyperparathyroidism: a medical perspective

The clinical phenotype of primary hyperparathyroidism in the United States has changed markedly over the past century, with the majority of patients having minimal overt symptomatology.It has become clear, however, that "asymptomatic" primary hyperparathyroidism is a disease with distinct physiologic characteristics.Data accumulated over recent years suggest that asymptomatic patients meeting specific criteria can be safely followed without surgery. These guidelines are elucidated, and new options in the medical therapeutics of primary hyperparathyroidism are discussed.     

Primary hyperparathyroidism: diagnostic and therapeutic trends

The most interesting aspects of parathyroid disease are the increased incidence of primary hyperparathyroidism, which nowadays is diagnosed more and more frequently through the casual discovery of hypercalcaemia, the various diagnostic methodologies used, the ongoing debate as to the function of parathyroidectomy in asymptomatic patients and the new video-assisted surgical techniques which have recently been developed. The authors retrospectively review 31 consecutive cases of primary hyperparathyroidism. The clinical onset was characterised in 26 cases by an osteoarthralgic syndrome associated with renal and biliary pathology. Five cases were asymptomatic. Prior to surgery, all patients underwent both biochemical and instrumental tests. MIB scintigraphy was found to yield the most reliable diagnosis, leading to identification of 83.6% of diseased parathyroids. As regards surgical treatment, 29 cases were treated with a simple parathyroidectomy, 1 with a bilateral inferior parathyroidectomy and 1 with a thyroid lobectomy. Associated thyroid surgery was performed in 8 cases for concomitant thyroid disease: 1 total thyroidectomy, 2 subtotal thyroidectomies and 5 lobectomies. In 3 cases radioimmunoguided surgery was used. There were no cases of mortality, and 9.6% of patients presented specific morbidity characterised by some degree of paraesthesia. As stated by other researchers, the authors argue that MIBI scintigraphy is the most reliable test for the diagnosis of hyperparathyroidism and that surgical treatment is the first choice for symptomatic primary hyperparathyroidism. The surgical strategy depends on the abnormality underlying the hyperparathyroidism: in the event off an adenoma, a bilateral exploration of the neck and removal of the diseased parathyroid are required; in the case of hyperplasia, a subtotal parathyroidectomy is necessary with marking of the residual parathyroid which will simplify any possible reoperation; in the event of carcinoma, a thyroid loboisthmectomy and ipsilateral parathyroidectomy are performed with removal of the fatty tissue of the antero-superior mediastinum and ipsilateral cervical functional lymphadenectomy.     

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??Asymptomatic primary hyperparathyroidism??Diagnosis and therapy ZHANG Hao. Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
Abstract As a result of a screening of serum calcium and and parathyroid hormone and neck ultrasound examination, the incidence of asymptomatic primary hyperparathyroidism (PHPT) has increased year by year. The diagnosis and therapy of asymptomatic PHPT gradually arouses extensive attention. Although there are still conflicts on the management of asymptomatic PHPT, it has become more standard with the accumulation of experience on asymptomatic PHPT, the development of clinical studies with higher intensity of argumentation, and the update of the guideline for the diagnosis and management of asymptomatic PHPT. The rational choose of surgery therapy, pharmacologic therapy and follow-up is the key to improve patients’ life quality and achieve the best therapy effects for patients with asymptomatic PHPT.     

Surgical exploration in asymptomatic hypercalcemia: Early treatment of hyperparathyroidism

The use of the serum auto-analyzer (SMA-12) has resulted in a marked increase in the diagnosis of hyperparathyroidism. Seventy-five patients with asymptomatic hypercalcemia were explored; sixty-eight with solitary adenomas, six with multiple adenomas, and one with diffuse hyperplasia. Postoperatively, all patients reverted to normocalcemia. Surgical exploration of asymptomatic hypercalcemia is advocated to reduce surgical morbidity and mortality and to prevent the development of renal and osseous complications of hyperparathyroidism.     

无症状型原发性甲状旁腺功能亢进临床诊治

随着血钙和血甲状旁腺素检测以及颈部超声检查的普遍开展,越来越多的无症状型原发性甲状旁腺功能亢进（PHPT）病人得以诊断,其诊断和治疗逐渐受到人们的广泛关注。尽管关于无症状型PHPT的处理方法尚存在一定争议,但随着诊治经验的积累、较高论证强度临床研究的开展以及诊治指南的不断更新,针对无症状型PHPT的处理变得愈加规范。手术治疗、药物治疗与随访观察的合理选择是改善无症状型PHPT病人生存质量,获得最佳治疗效果的关键。     

Indications for surgery in the elderly patient with primary hyperparathyroidism.

The major symptoms presented by the elderly patient with primary hyperparathyroidism (HPT) were studied in 30 patients, all of whom were over 70 years of age (70-89). Neuromuscular symptoms, fatigue or mental symptoms were the main complaint in 14 patients. Nephrolithiasis, pancreatitis, skeletal changes or thyroid diseases were associated with HPT in 13 patients. Three patients were considered to be asymptomatic. Seven out of the eight patients with neuromuscular symptoms, and two of the three patients with extreme fatigue as the dominant symptom, improved postoperatively. This study indicates that for elderly patients with HPT especially when associated with neuromuscular symptoms or fatigue, surgical therapy is the treatment of choice.     

Aggressive Pulmonary Calcification Developed After Living Donor Kidney Transplantation in a Patient With Primary Hyperparathyroidism

Metastatic pulmonary calcification, defined as calcium deposition in the intact lung, is commonly seen in patients with chronic renal failure, and it is known to be a benign clinical condition when detected by chance in an asymptomatic patient. Here we report the case of a 33-year-old woman who developed rapid and aggressive metastatic pulmonary calcification shortly after a living donor kidney transplantation, which induced acute antibody-mediated rejection. The patient's metastatic pulmonary calcification was successfully improved by extensive treatment for graft rejection, the correction of her accompanying primary hyperparathyroidism, and medical treatment with a bisphosphonate and sodium thiosulfate. Aggressive pulmonary calcification is reported as a rare complication seen in patients who have undergone a failed renal transplantation. A failed renal graft and accompanying secondary hyperparathyroidism seem to accelerate metastatic calcification. Most of the patients who develop aggressive pulmonary calcification suffer from the rapid progression of dyspnea and occasionally fever, and they die of respiratory failure. Pulmonary calcification should be considered in a patient developing dyspnea and unexplained pulmonary infiltrate, especially in the context of renal graft rejection; otherwise the prognosis of the patient will be very poor.     

Canadian Association of General Surgeons and American College of Surgeons Evidence Based Reviews in Surgery. 16. Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism.

Question: Is quality of life improved in patients who have a parathyroidectomy for mild asymptomatic primary hyperparathyroidism? Design: A randomized controlled trial. Setting: Single centre trial, Henry Ford Health System, Detroit, Mich. Patients: Fifty-three patients (42 women, 11 men) with confirmed asymptomatic primary hyperparathyroidism defined as follows: persistent albumin-adjusted serum calcium level of 10.1–11.5 mg/dL (2.5– 2.9 mmol/L) from at least 3 measurements over a period of at least 3 months with an intact parathyroid hormone level that was greater than 20 pg/mL (> 2.1 pmol/L) and no other cause of hypercalcemia. Interventions: Patients were randomly allocated to receive either careful observation (n = 28) or surgery (n = 25). Those in the surgery group underwent a standard parathyroidectomy with bilateral approach by a single experienced surgeon who had performed over 600 parathyroid procedures before the study. Main outcome measure: Nine domains of the SF-36 Health Survey were measured to assess health-related quality of life. Results: The parathyroidectomy group had significantly better quality of life in 2 of the 9 domains of the SF-36: social functioning (p = 0.007) and role functioning — emotional (p = 0.012). Conclusions: Improved quality of life is seen after a parathyroidectomy for mild asymptomatic primary hyperparathyroidism and supports surgical management of mild primary hyperparathyroidism.     

Importance of a fifth parathyroid gland in the surgical treatment of hyperparathyroidism

Of 365 patients surgically treated for hyperparathyroidism at the University of Toronto hospitals, 3 had hypercalcemia due to an abnormal and ectopic fifth parathyroid gland. Autopsy studies have shown that a fifth gland may be present in 3% to 5% of patients with hyperparathyroidism. The possibility of an abnormal fifth gland as the cause of primary hyperparathyroidism should be considered when four glands of normal size and histology have been found in the neck, and such a gland should be sought in all patients with the diffuse hyperplasia of secondary hyperparathyroidism. The fifth gland is usually in the lower neck or upper mediastinum, frequently within the thymus. If present, it can usually be recognized and excised.     

Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy. A case-control study.

BACKGROUND: There has been an National Institutes of Health consensus meeting concerning the management of patients with "asymptomatic" primary hyperparathyroidism, yet there is no clear definition of this condition. The authors, therefore, documented the clinical manifestations and frequencies of these manifestations in unselected patients with primary hyperparathyroidism and determined whether these clinical manifestations resolved after parathyroidectomy. METHOD: The authors studied 152 unselected consecutive patients with primary hyperparathyroidism and 132 control patients with nontoxic thyroid disorders who were treated by parathyroidectomy or thyroidectomy, respectively, between January 1986 and June 1991. All patients received a questionnaire during their initial office visits and the same questionnaire again after their operations. Patients were also questioned about their perception of the success of the operation. Eighty percent of the parathyroid patients and 70.5% of the thyroid patients completed the questionnaires, and the mean follow-up time was 20 months. RESULTS: Only 7 (4.6%) patients with primary hyperparathyroidism had no symptoms, and 26 (17.1%) had no associated conditions despite 74.3% of these patients having serum calcium levels less than 12 mg/dL. Symptoms including fatigue, exhaustion, weakness, polydipsia, polyuria, nocturia, joint pain, bone pain, constipation, depression, anorexia, nausea, heartburn, and associated conditions, including nephrolithiasis, and hematuria occurred more often in patients with primary hyperparathyroidism than in the thyroid control patients (p < 0.05). After parathyroidectomy, only eight (5.3%) patients failed to have any improvement in symptoms or associated conditions. Fifty-seven percent of the parathyroid patients versus 30% of the thyroid patients felt better overall after the operation, strength subjectively improved in 29% of parathyroid patients versus 13% in thyroid patients; thirty-seven percent of the parathyroid patients versus 13% of the thyroid patients claimed they were less depressed. CONCLUSION: When examined thoroughly, few patients with primary hyperparathyroidism were asymptomatic or without associated conditions, and most patients experienced subjective improvement after successful parathyroidectomy.     

Surgical Treatment of Primary Hyperparathyroidism: Description of Techniques and Advances in the Field

Primary hyperparathyroidism is a disease commonly seen in patients above 60 years of age. It is the most common cause of asymptomatic or symptomatic hypercalcemia, usually found incidentally on routine check-ups. Surgical treatment is the only definitive treatment of choice in the symptomatic patient; however, it can also be employed in asymptomatic patients. First described in 1925, bilateral neck exploration is the gold standard of treatment for primary hyperparathyroidism. The recent interest in minimally invasive surgeries has led to better and improved techniques of neck exploration with improved cosmetic results and lesser chances of transient or permanent hypoparathyroidism due to inadvertent removal of normally functioning parathyroid tissue. These include unilateral neck explorations, minimally invasive parathyroidectomies and minimally invasive radio-guided parathyroidectomy. The intact parathyroid hormone assays have greatly added to the detection of normal and abnormal functioning glands, hence better surgical outcomes.     

Tertiary hyperparathyroidism after renal transplantation: operative indications

A retrospective analysis of our renal transplant population between 1981 and 1987 was undertaken to study the natural history of posttransplant hypercalcemia and to review indications and recommendations regarding the timing of parathyroidectomy. During this period, 1158 renal transplant procedures were performed in 1025 patients, with 819 allografts (71%) functioning currently. Posttransplant hypercalcemia greater than 10.5 mg/dl was associated with a longer duration of dialysis and developed in 227 patients, with onset of hypercalcemia occurring in 90% of these patients by 1 year. In 69% of these patients, spontaneous resolution of the hypercalcemia occurred between 6 months and 7 years after transplantation. A total of 42 patients with asymptomatic hypercalcemia are currently being followed up, with a mean serum calcium level of 11.0 +/- 0.41 mg/dl and a mean follow-up interval of 3.3 +/- 1.6 years since transplantation. Nine symptom-free patients with moderate hypercalcemia (12.0 to 12.4 mg/dl) more than 1 year after transplantation were identified. Five of these patients had spontaneous resolution of the hypercalcemia between 2 and 7 years. Fifteen patients with posttransplant hyperparathyroidism (6.6%) required parathyroidectomy--11 for symptomatic and four for asymptomatic hyperparathyroidism. One patient had symptomatic hyperparathyroidism despite the presence of normocalcemia. One symptom-free patient with significant hypercalcemia (serum calcium level, 14.7 mg/dl) underwent parathyroidectomy 3 months after transplantation. The remaining three symptom-free patients had serum calcium determinations of greater than or equal to 12.5 mg/dl more than 1 year after renal transplantation. Patients with pretransplant and posttransplant hypercalcemia required parathyroidectomy more frequently than did patients with only posttransplant hypercalcemia (18% versus 3.0%; p less than 0.001). An unusual finding was the occurrence of a single adenoma in two patients, which represents sporadic primary hyperparathyroidism in the patient undergoing renal transplantation rather than tertiary hyperparathyroidism. We recommend a conservative approach to posttransplant hypercalcemia, with surgery reserved for patients with symptomatic disease and patients with asymptomatic persistent hypercalcemia greater than or equal to 12.5 mg/dl more than 1 year after transplantation.     

Surgery for secondary hyperparathyroidism in patients undergoing dialysis

Despite recent advances in the diagnosis and therapy of patients with chronic renal failure and secondary hyperparathyroidism (HPT), 5% of these patients may need parathyroidectomy. The purpose of this article is to present our experience with parathyroid surgery in 30 patients with chronic renal failure at "La Paz" University Hospital, analyzing the clinical and biochemical evolution after surgery as well as the recurrence rate. In the first month after surgery, calcium, parathyroid hormone, phosphorus, and alkaline phosphatase levels, as well as bone pain and pruritus, all decreased significantly. Within the first postoperative year, 24 patients remained asymptomatic, and no recurrent secondary HPT was detected. Within the second year after surgery, 15 patients were asymptomatic, and 3 patients showed a recurrence. According to these results, parathyroidectomy is an appropriate surgical procedure for patients with severe overt secondary HPT.