Pia Lindblom

Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial.

ObjectiveTo compare unilateral and bilateral neck exploration for primary hyperparathyroidism in a prospective randomized controlled trial. Summary Background DataBased on the assumption that unilateral neck exploration for a solitary parathyroid adenoma should reduce operating time and morbidity, a variety of minimally invasive procedures have challenged the idea that bilateral neck exploration is the gold standard for the surgical treatment of primary hyperparathyroidism. However, to date, no open prospective randomized trial has been published comparing unilateral and bilateral neck exploration. MethodsNinety-one patients with the preoperative diagnosis of primary hyperparathyroidism were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. The primary end-point was the use of postoperative medication for hypocalcemic symptoms. ResultsEighty-eight patients (97%) were cured. Histology and cure rate did not differ between the two groups. Patients in the bilateral group consumed more oral calcium, had lower serum calcium values on postoperative days 1 to 4, and had a higher incidence of early severe symptomatic hypocalcemia compared with patients in the unilateral group. In addition, for patients undergoing surgery for a solitary parathyroid adenoma, unilateral exploration was associated with a shorter operative time. The cost for the two procedures did not differ. ConclusionsPatients undergoing a unilateral procedure had a lower incidence of biochemical and severe symptomatic hypocalcemia in the early postoperative period compared with patients undergoing bilateral exploration. Unilateral neck exploration with intraoperative parathyroid hormone assessment is a valid surgical strategy in patients with primary hyperparathyroidism with distinct advantages, especially for patients with solitary parathyroid adenoma.

Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment.

Valdemarsson S, Lindblom P, Bergenfelz A (Departments of Internal medicine and surgery, Lund University Hospital, Lund Sweden). Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 1998; 244: 241–49.

Sestamibi versus thallium subtraction scintigraphy in parathyroid localization : a prospective comparative study in patients with predominantly mild primary hyperparathyroidism

BACKGROUND Technetium 99m sestamibi was recently introduced for the preoperative localization of abnormal parathyroid glands in patients with primary hyperparathyroidism with promising results. However, the sensitivity of sestamibi and thallium to detect abnormal parathyroid glands is partly dependent on the gland size. In this study we compared the sensitivity of sestamibi subtraction scintigraphy with thallium subtraction scintigraphy in patients with predominantly mild increase in serum calcium level. METHODS Thirty-nine patients with primary hyperparathyroidism were included. The mean (+/-SD) serum level of calcium was 2.75 +/- 0.17 mmol/L. In 28 (72%) of the patients the serum level of calcium was less than 2.85 mmol/L. These patients were classified as having mild abnormalities in serum calcium. All patients were investigated before operation with both sestamibi and thallium subtraction scintigraphy. RESULTS In two patients autonomous thyroid adenomas precluded subtraction scintigraphy. Sestamibi subtraction scintigraphy correctly localized 31 (86%) of 36 parathyroid adenomas compared with only 17 (47%) of 36 by thallium subtraction scintigraphy (p < 0.001). There was one false-positive result in the sestamibi group because of a thyroid adenoma, and two of the scans were negative. Both the sestamibi and the thallium subtraction scintigraphy localized one single enlarged gland in all three patients with multiple gland involvement. In no case was multiglandular disease predicted. CONCLUSIONS Sestamibi subtraction scintigraphy is superior to thallium subtraction scintigraphy and has a high sensitivity to localize a solitary parathyroid adenoma in patients with mild increase in serum calcium level. The sensitivity decreases in patients with multiglandular parathyroid disease and concomitant thyroid nodular abnormalities.

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.

Postoperative Elevated Serum Levels of Intact Parathyroid Hormone after Surgery for Parathyroid Adenoma: Sign of Bone Remineralization and Decreased Calcium Absorption

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.

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.

Preoperative normal level of parathyroid hormone signifies an early and mild form of primary hyperparathyroidism.

Contemporary patients are often diagnosed with mild or intermittent hypercalcemia. In addition, most studies demonstrate patients with parathyroid (PTH) levels in the upper normal range. The aim of the present investigation was to define subgroups of patients with mild primary hyperparathyroidism (pHPT), which could be of importance in the decision for or against surgical treatment. Two-hundred and eleven patients, operated for pHPT were investigated with biochemical variables known to reflect PTH activity, renal function, and bone mineral content. The preoperative diagnosis of pHPT was based on the presence of hypercalcemia combined with an inappropriate serum concentration of PTH. The mean age of the patients was 64 ± 14 years and the mean serum level of calcium was 2.78 ± 0.19 mmol/L. One hundred and sixty-two patients (77%) had raised levels of calcium and PTH the day before surgery (overt pHPT), 25 patients (12%) had a normal level of calcium and a raised PTH level (normal calcium group), and 20 patients (9%) had a raised level of calcium and a normal level of PTH (normal PTH group). In four patients the level of calcium and PTH was normal. Between-group analysis demonstrated no major difference in symptom and signs of pHPT. Except for lower adenoma weight, patients in the normal calcium group did not essentially differ from the patients in the overt pHPT group. However, patients in the normal PTH group were a decade younger, and had better renal function, lower bone turnover, and a preserved bone density compared with patients in the overt pHPT group. In conclusion, the data from the present investigation show that pHPT patients with a preoperative normal PTH level have an early and mild form of the disease. Furthermore, the serum calcium concentration does not reflect disease severity in pHPT.

Hyperthyroidism after surgery for primary hyperparathyroidism

Abstract  Background: The coexistence of hyperthyroidism and primary hyperparathyroidism (pHPT) has been reported. We have questioned whether hypercalcemia or surgical trauma contribute to transient hyperthyroidism following parathyroid surgery. Methods: Twenty-six pHPT and eleven breast cancer patients were compared regarding pre-, peri- and postoperative thyrotropin (TSH), free thyroxine (T4) and free triiodothyronine (T3) concentrations. Thyroglobulin concentration, occurrence of autonomous thyroid nodules, and variables reflecting surgical trauma were compared in pHPT patients with and without postoperative hyperthyroidism. Results: Postoperatively, eleven pHPT patients demonstrated T4 and T3 concentrations above normal, and nine developed symptoms of mild thyrotoxicosis. A parallel rise in TSH and T4 concentrations was seen during both parathyroid and breast cancer surgery. Compared with patients with no postoperative hyperthyroidism, patients with postoperative hyperthyroidism showed a parallell rise in mean thyroglobulin and T4/T3 concentrations as well as higher thyroglobulin concentrations. However, there was no difference in variables assessing surgical trauma nor in occurrence of autonomous thyroid nodules. The peri-operative rise in TSH was preceded by a decrease in calcium. Conclusion: Transient hyperthyroidism after parathyroid surgery is not infrequent. The condition seems to be self-limiting, since symptoms invariably subsided without treatment. Manipulation of the thyroid gland is most likely the major contributing factor to postoperative hyperthyroidism. However, it may not be the sole explanation, since our data suggest a more multifactorial scenario.

Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

BackgroundDisseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer.MethodsBetween 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately.ResultsDTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples.ConclusionsThe detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.

Urate and arteriosclerosis in primary hyperparathyroidism

OBJECTIVE An increased mortality due to cardiovascular disease has been reported in patients with primary hyperparathyroidism (pHPT). An association between urate and cardiovascular disease has been suggested. Metabolic abnormalities in pHPT may include urate. We therefore evaluated the metabolic arteriosclerotic risk profile in pHPT with special focus on the role of urate.