Erik Nordenström

Multifactorial risk profile for bone fractures in primary hyperparathyroidism

Primary hyperparathyroidism (pHPT) is associated with an increased fracture risk, and decreased bone density thus has been considered an indication for surgery. However, many pHPT patients have a multifactorial risk profile for osteoporosis and bone fractures. The aim of the present study was to evaluate variables associated with fracture risk within the group of pHPT patients. A series of 203 consecutive patients operated for pHPT were investigated with bone mineral content and biochemical and clinical risk factors for bone fracture. Seventeen patients (8%) had a history of at least one bone fracture up to 5 years before pHPT surgery. Twenty-six patients (13%) had a history of at least one fracture during the 10-year period prior to surgery. In the univariate analyses corticosteroid treatment, serum levels of alkaline phosphatase, 25-hydroxyvitamin D3, type I collagen telopeptide, and bone mineral content were found to be associated with a history of bone fractures up to 10 years before surgery. Additionally, age and menopausal status were of importance for fractures during the 10-year-period, whereas a history of cardiovascular disease was important for fractures during the 5-year-period prior to surgery. Multivariate analyses showed that serum level of PTH was independently associated with bone fractures during the 5-year period prior to pHPT surgery and further that serum level of 25-hydroxyvitamin D3 was associated with fractures up to 10 years before surgery. In conclusion, serum levels of 25-hydroxyvitamin D3 and PTH were independently associated with a history of bone fractures in pHPT. These variables should be considered when evaluating patients for parathyroid surgery.RésuméL’hyperparathyroïdie primitive (pHPT) est associée à un risque accru de fracture en rapport avec une densité osseuse diminuée et ainsi est considérée comme une bonne indication de la chirurgie. Cependant, beaucoup de patients pHPT ont un profil de risque multifactoriel d’ostéoporose et de fractures. Le but de cette étude a été d’évaluer les variables associées au risque de fracture dans le groupe de patients pHPT. On a évalué chez 203 patients consécutifs opérés pour pHPT le contenu minéral osseux (bone mineral content (BMC)), ainsi que les facteurs de risque de fracture osseuse, biochemique et clinique. Dix-sept patients (8%) avaient une histoire d’au moins une fracture osseuse dans les cinq ans précédant la chirurgie pour pHPT. Vingt-six patients (13%) avaient une histoire d’au moins une fracture osseuse dans les dix ans précédant la chirurgie. Par analyse univariée, on a démontré que le traitement par corticostéroïdes, les niveaux sériques de phosphatases alcalines, les taux de 25-hydroxyvitamine D3, le collagène télopeptide de type I et le BMC étaient associés à une histoire de fracture osseuse dans les dix ans précédant la chirurgie. De même, l’âge et l’état de ménopause étaient des facteurs pronostiques importants dans la période des dix ans précédant la chirurgie alors que la maladie cardiovasculaire était un facteur important dans la période de cinq ans précédant la chirurgie. Par analyse multivariée, on a trouvé que le taux sérique de PTH était un facteur indépendant de fracture osseuse dans la péroide de cinq ans précédant la chirurgie pour pHPT et également, que le taux sérique de 25-hydroxyvitamine D3 était un facteur pronostique indépendant dans la période de dix ans précédant la chirurgie. En conclusion, les taux sériques de la 25-hydroxyvitamine D3 et de la PTH étaient des facteurs de risque indépendants de fracture osseuse en cas de pHPT. Ces données doivent être prises en compte lors de l’évaluation de patients opérés de leur parathyroïde.ResumenEl hiperparatiroidismo primario (HPTp) se acompañ de riesgo aumentado de fracturas, por lo cual la demostración de densidad ósea disminuida de por sí, ha sido considerada como indicación para cirugía. Sin embargo, muchos pacientes con HPTp tienen un perfil de riesgo de osteoporosis y fracturas óseas multifactorial. El propósito del presente estudio fue evaluar las variables asociadas con riesgo de fracturas en el grupo de pacientes con HPTp. Doscientos tres pacientes consecutivos operados por HPTp fueron estudiados en cuanto a contenido mineral y a factores bioquímicos y clínicos de riesgo de fractura ósea. Diecisiete pacientes (8%) tenían historia de por lo menos una fractura hasta 5 años previos de la cirugía para HPTp. Veintiséis (13%) tenían historia de por lo menos una fractura en el curso de los 10 años anteriores a la cirugía. El análisis multivariado mostró que la terapia con corticoïdes, los niveles séricos de fosfatasa alcalina, de 25 hidroxivitamina D3, el telopéptido colagenoso Tipo ï y el contenido mineral del hueso se asocian con historia de fracturas hasta por 10 años antes de la cirugía. El análisis multivariado mostró que los niveles séricos de paratohormona se hallan independientemente asociados con fracturas óseas en el quinquenio anterior a la cirugía y, además, que los niveles séricos de 25-hidroxivitamina D3 se asocian con fracturas hasta por 10 años previos a la cirugía. En conclusión, los niveles séricos de 25-hidroxivitamina D3 y de paratohormona se hallan independientemente asociados con historia de fracturas óseas en el HPTp. Estas variables deben ser tenidas en cuenta cuando se evalúa un paciente para cirugía paratiroidea.

Recovery of Bone Mineral Density in 126 Patients after Surgery for Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is associated with increased fracture risk and decreased bone mass. The recovery of bone mass after surgery varies; therefore tests that predict the increase in bone mass after parathyroidectomy would be desirable. Preoperatively and at 1 year after surgery bone mineral content (BMC) in the distal radius and bone mineral density (BMD) in the lumbar spine and hip, as well as biochemical variables, were measured in 126 pHPT patients (95 women, 31 men). The mean ± SD age of the patients was 63 ± 15 years. The mean ± SD serum calcium level was 2.78 ± 0.16 mmol/L. Altogether, 60% of the patients had a low oral calcium intake, and 18% had a 25-hydroxyvitamin D3 deficiency. Preoperatively, postmenopausal women had lower Z-scores for BMD in the hip (p < 0.001) and lumbar spine (p < 0.05) than did premenopausal women. One year after surgery the bone density had increased in about 50% of the patients. The multiple logistic regression analysis showed that there was a weak association between the change in BMD in the hip, the serum 1,25-dihydroxyvitamin D3 level (p < 0.05), and renal function (p < 0.05), respectively. We concluded that about 50% of patients have increased bone mass after pHPT surgery, but the increase in the bone density is difficult to predict for the individual patient. Because many pHPT patients have low oral calcium intake and a vitamin D deficiency, it would be of interest to evaluate the role of postoperative calcium/vitamin D supplements.

Changing biochemical presentation of primary hyperparathyroidism

PurposePatients 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.MethodsThere 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.ResultsPreoperative 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.ConclusionFrom 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.

Patients with elevated serum parathyroid hormone levels after parathyroidectomy: showing signs of decreased peripheral parathyroid hormone sensitivity.

We have previously shown that patients with elevated levels of parathyroid hormone (PTH) after surgery for parathyroid adenoma have normal parathyroid and renal function but demonstrate signs of remineralization of cortical bone, decreased calcium absorption, and low levels of vitamin D. We hypothesized that decreased peripheral PTH sensitivity could also be of importance for this condition. Thirteen patients operated on for a solitary parathyroid adenoma, with a mean ± SD preoperative serum level of calcium of 2.72 ± 0.12 mmol/L, were investigated 6 weeks after surgery with a standardized PTH (1-34) infusion test for 6 hours. The eight patients with elevated PTH levels had less increase in serum levels of ionized calcium (0.02 ± 0.03 mmol/L) than did the five patients with normal PTH levels (0.06 ± 0.02 mmol/L) (p < 0.05). Patients with elevated PTH also showed less decrease in serum phosphate levels (p < 0.05) and a trend to a larger decrease in the excretion of urinary calcium (p = 0.08). The increase in 1,25-dihydroxyvitamin D3 did not differ between the two groups of patients. Thus patients operated on for parathyroid adenoma with postoperatively elevated serum PTH levels showed decreased peripheral sensitivity to PTH.

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 group’s 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.

Biochemical diagnosis of primary hyperparathyroidism: Analysis of the sensitivity of total and ionized calcium in combination with PTH.

OBJECTIVES To investigate the accuracy of the biochemical diagnosis of primary hyperparathyroidism (pHPT) in a consecutive series of patients with operatively verified disease. DESIGN AND SUBJECTS Four hundred thirty-six patients with pHPT, 340 women and 96 men, were reviewed. Biochemical variables, including total calcium (Ca), ionized calcium (Cai) and PTH were analyzed and registered in a prospective database. RESULTS In the subgroup of patients with more mild hypercalcemia (Ca below 2.70mmol/L) the correlation between Ca and Cai was poor. 19 respectively 18 patients had preoperatively a Ca respectively Cai level within the reference range. Further 35 patients had preoperatively a normal level of PTH. The diagnostic sensitivities, in detecting pHPT, for Ca, Cai and the combination of Ca and Cai were 96%, 96% and 99%. CONCLUSION If calcium and ionized calcium are not used in the diagnostic workup of pHPT some 4% of the patients will be overlooked. We recommend analyzing both Ca and Cai in the diagnostic workup of pHPT.

Risk of recurrent laryngeal nerve palsy in patients undergoing thyroidectomy with and without intraoperative nerve monitoring

Vocal cord palsy occurs in 3–5 per cent of patients after thyroidectomy. To reduce this complication, intraoperative nerve monitoring (IONM) has been introduced, although its use remains controversial. This study investigated the risk of postoperative vocal cord palsy with and without the use of intermittent IONM.

Serum Levels of Uric Acid and Diabetes Mellitus Influence Survival after Surgery for Primary Hyperparathyroidism: A Prospective Cohort Study

BackgroundPrimary hyperparathyroidism (pHPT) is associated with an increased mortality attributable to cardiovascular disease (CVD), suggested to be alleviated by surgery. The exact mechanism of the beneficial influence of parathyroidectomy on survival is unknown. Furthermore, studies suggest that there is no increased mortality compared to the mortality rate in the general population during recent years. This study therefore investigated relative survival (RS), as well overall mortality associated with the clinical and biochemical variables in patients undergoing operation for sporadic pHPT. Furthermore, the influence of surgery on biochemical variables associated with pHPT was analyzed.MethodsA group of 323 patients with sporadic pHPT operated between September 1989 and July 2003 were followed from surgery over a 10-year period. The median and mean follow-up time was 69 and 70 months, respectively (range: 1–120 months). Relative survival (RS) was calculated, and the impact of clinical and biochemical variables on overall death were evaluated.ResultsPostoperatively, serum levels of triglycerides and uric acid decreased. Glucose levels and glomerular filtration rate remained unchanged. A decreased RS was evident during the latter part of the 10 year follow-up period. In the multivariate Cox-analysis, diabetes mellitus (hazard ratio [HR] = 2.8, 95%; confidence interval [CI] 1.2–6.7), and the combination of an increased level of serum uric acid and cardiovascular disease (CVD) (HR = 8.6, 95%; CI 1.5–49.7) was associated with a higher mortality. The increased risk of death was evident for patients with persistently increased levels of uric acid postoperatively (HR = 4.8, 95%; CI = 1.4–16.01)ConclusionsPatients undergoing operation for pHPT had a decreased RS during a 10-year follow-up compared to the general population. This decrease in RS is associated with diabetes mellitus and increased levels of uric acid pre-and postoperatively.

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.

Determinants for malignancy in surgically treated adrenal lesions.

PurposeIt is difficult to definitively rule out or establish malignancy pre-operatively in patients with adrenal lesions referred for adrenal surgery. The aim of this study was to identify risk factors for a malignant diagnosis in patients treated with adrenalectomy.MethodsConsecutive adrenalectomies at the Department of Surgery, Lund University Hospital between 2000 and 2009 were identified. Pre-operative clinical, radiological and biochemical data, as well as details on the operation and histology, were retrieved from patients’ medical records.ResultsThere were 175 adrenal operations in 172 patients (98 female and 77 male). There were 28 malignancies. Malignant tumours were larger than in benign cases (p = 0.003), had radiological signs of malignancy more often (p = 0.001) and the patients were more likely to have a history of malignancy (p = 0.001). There were no differences regarding age, gender, body mass index or mode of detection (incidental vs. clinical) between patients with benign and malignant diagnoses. A unilateral uptake on fluorine-18 deoxyglucose positron emission tomography was more frequent in malignant cases than in benign; however, this association did not reach statistical significance.ConclusionsSize of adrenal lesion, suspicious radiological findings and history of malignancy were factors associated with malignancy.