Positive Effect of Parathyroidectomy Compared to Observation on BMD in a Randomized Controlled Trial of Mild Primary Hyperparathyroidism.

Mild or asymptomatic disease is now the dominating presentation of primary hyperparathyroidism (PHPT). However, bone involvement with decreased bone mineral density (BMD) and an increased risk of fractures has been demonstrated. Indications for parathyroidectomy (PTX) in mild PHPT have been debated for years. There is a need of long-term randomized studies comparing PTX with observation without intervention (OBS). Here, we present bone health data from the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH), a randomized controlled trial, comparing PTX to OBS. This study included 191 patients (96 OBS/95 PTX), and 129 patients (64 OBS/65 PTX) were followed for 10 years to the end of study (EOS). BMD was measured with dual-energy X-ray absorptiometry (DXA), peripheral fractures were noted, and spine radiographs were obtained for vertebral fracture assessment. There was a significant treatment effect of PTX on BMD compared with OBS for all analyzed compartments, most explicit for the lumbar spine (LS) and femoral neck (FN) (p < 0.001). The mean changes in T-score from baseline to 10 years were from 0.41 for radius 33% (Rad33) to 0.58 for LS greater in the PTX group than in the OBS group. There was a significant decrease in BMD for all compartments in the OBS group, most pronounced for FN, Rad33, and ultradistal radius (UDR) (p < 0.001). Even though there was a significant treatment effect of PTX compared with OBS, there was only a significant increase in BMD over time for LS (p < 0.001). We found no difference between groups in fracture frequency in the 10-year cohort, neither with modified intention-to-treat (mITT) analysis nor per protocol analysis. Because BMD is only a surrogate endpoint of bone health and PTX did not reduce fracture risk, observation could be considered a safe option for many patients with mild PHPT regarding bone health in a 10-year perspective. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

Effects of Parathyroidectomy on Quality of Life: 10 Years of Data From a Prospective Randomized Controlled Trial on Primary Hyperparathyroidism (the SIPH-Study).

Primary hyperparathyroidism (PHPT) was previously considered a disease presenting with multiorgan involvement and a wide range of symptoms. Today, the disease presents with no symptoms or mild symptomatology in most patients. Data regarding nonspecific symptoms such as pain, fatigue, memory loss, depression, and other neuropsychiatric signs have been ambiguous, and results from prospective long-term randomized control trials are lacking. The Scandinavian Investigation on Primary Hyperparathyroidism (SIPH) is a prospective randomized controlled trial (RCT) with 10-year follow up, comparing parathyroidectomy (PTX) to observation without any treatment (OBS). From 1998 to 2005, 191 patients with mild PHPT were included from Sweden, Norway, and Denmark. A total of 95 patients were randomized to PTX and 96 to OBS. The generic Short Form-36 survey (SF-36) and the Comprehensive Psychopathological Rating Scale (CPRS) were studied at baseline, 2, 5, and 10 years after randomization. After 10 years, the PTX group scored significantly better on vitality (PTX 65.1 ± 20.2 versus OBS 57.4 ± 22.7; p = .017) compared to the OBS group in SF-36. We found no differences between the groups in the physical subscales. The OBS group had no significant change in any of the SF-36 scores throughout the study. The CPRS showed an improvement of symptoms in both groups for single items and sum scores after 10 years compared to baseline. There were, however, no significant differences between the two groups in the CPRS data. The results of this large and long-term RCT indicate improvement in some of the mental domains of SF-36 following PTX. However, the treatment effects between the groups were subtle with uncertain clinical significance. The observation group had stable SF-36 values and improvement in CPRS symptom-scores. Thus, in considering only quality of life (QoL) and in the absence of declines in renal and skeletal parameters, it may be safe to observe patients with mild PHPT for a decade. © 2020 American Society for Bone and Mineral Research (ASBMR).

Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations.

INTRODUCTION: Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. MATERIAL AND METHODS: Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. RESULTS: Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [3 H]thymidine in cultured granulosa cells. CONCLUSIONS: Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.

The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism

Context: Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective: To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design, patients, interventions, main outcome measures: 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results: In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion: In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.

Effect of Surgery Versus Observation: Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study).

Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm2 and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p < 0.001) and CTX-1 (p < 0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm2 ) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p < 0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p < 0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm2 ) for all compartments (FN, p < 0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p < 0.001) with the exception of the LS, where BMD was stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT. © 2017 American Society for Bone and Mineral Research.

Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study.

BACKGROUND: Energy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time. MATERIALS AND METHODS: The Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88% of the thyroid procedures performed during 2008­2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used. RESULTS: The thyroid procedures performed included C-A-T (16.6%), bipolar electrosurgery (ES: 56.5%), electronic vessel sealing (EVS: 12.2%), and ultrasonic dissection (UD: 14.5%). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T. CONCLUSION: In this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.

Revising the embryonic origin of thyroid C cells in mice and humans.

Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail-chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca(2+) homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development.

Effects of parathyroidectomy versus observation on the development of vertebral fractures in mild primary hyperparathyroidism.

CONTEXT: Mild primary hyperparathyroidism (PHPT) is a common disease especially in middle-aged and elderly women. The diagnosis is frequently made incidentally and treatment strategies are widely discussed. OBJECTIVE: To study the effect of parathyroidectomy (PTX) compared with observation (OBS) on biochemistry, safety, bone mineral density (BMD), and new fractures. DESIGN: Prospective, randomized controlled study (SIPH study), with a 5-year follow-up. SETTING: The study was conducted at multicenter, tertiary referral centers. PATIENTS: Of 191 randomized patients with mild PHPT, biochemical data were available for 145 patients after 5 years, with a mean age at inclusion of 62.8 years (OBS group, 9 males) and 62.1 years (PTX group, 10 males). INTERVENTION: Parathyroidectomy vs observation. MAIN OUTCOME MEASURES: Biochemistry, BMD, and new radiographic vertebral fractures. RESULTS: Serum-calcium and PTH-levels normalized after surgery and did not deteriorate by observation. BMD Z-scores were normal at inclusion in the lumbar spine (LS) and femoral neck (FN). For LS, BMD Z-scores were stable for 5 years with observation, but decreased in FN (P < .02). After surgery, BMD Z-scores increased significantly in both compartments (P < .02 for both), with a highly significant treatment effect of surgery compared to observation (P < .001). During follow-up, five new clinically unrecognized vertebral fractures were found in 5 females, all in the OBS group (P = .058). CONCLUSION: Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.

Quality of life and health care consumption in primary care patients with elevated serum calcium concentrations in - a prospective, case control, study.

BACKGROUND: Patients with elevated calcium concentrations have an increased morbidity due to various underlying illnesses. However, there is a lack of studies of quality of life and health care consumption in patients with hypercalcaemia per se. The study aims to investigate quality of life and health care consumption, as measured by, sick leave, drug prescriptions and the number of visits and admissions to health care centres and hospitals, in primary care patients with elevated calcium concentrations. METHODS: A prospective, case control, study in primary care centre, in Sweden. Patients with elevated, (n=127, 28 men), and normal calcium concentrations, (n=254, 56 men), mean age 61.4 year, were recruited in the study and followed during 10 years. Eighty-six percent of those alive at the time of follow up participated in a follow up visit. The study participants completed a quality of life survey, SF-36, which also were compared with the Swedish SF-36 national normative database. RESULTS: Patients with elevated calcium concentrations had significantly lower quality of life both compared with the control group (patients with normal calcium concentrations) and compared with age and gender-matched reference material from the Swedish SF-36 national normative database. The group with elevated calcium concentrations had significantly more hospitalisations (p=0.017), subsequently cancer diagnoses (p<0.003), sick leave (p=0.007) and medication (p=0.002) compared with patients with normal calcium concentrations. Men with elevated calcium concentrations had more contacts with the psychosocial team (p=0.02) at the health care centre. CONCLUSIONS: Elevated calcium concentrations are associated with significantly reduced quality of life and increased health care consumption and should therefore be an important warning flag that should alert the physician to further investigate and care for the patient. This is the first study in this field and the results need to be confirmed in further studies.

Multifocal papillary thyroid carcinoma--a consensus report of the European Society of Endocrine Surgeons (ESES).

BACKGROUND: Multifocal papillary thyroid carcinoma (MPTC) has been reported in literature in 18-87 % of cases. This paper aims to review controversies in the molecular pathogenesis, prognosis, and management of MPTC. METHODS: A review of English-language literature focusing on MPTC was carried out, and analyzed in an evidence-based perspective. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to surgery of thyroid carcinoma. RESULTS: Literature reports no prospective randomized studies; thus, a relatively low level of evidence may be achieved. CONCLUSIONS: MPTC could be the result of either true multicentricity or intrathyroidal metastasis from a single malignant focus. Radiation and familial nonmedullary thyroid carcinoma are conditions at risk of MPTC development. The prognostic importance of multifocal tumor growth in PTC remains controversial. Prognosis might be impaired in clinical MPTC but less or none in MPTC <1 cm. MPTC can be diagnosed preoperatively by FNAB and US, with low sensitivity for MPTC <1 cm. Total or near-total thyroidectomy is indicated to reduce the risk of local recurrence. Prophylactic central node dissection should be considered in patients with total tumor diameter >1 cm, or in cases with high number of cancer foci. Completion thyroidectomy might be necessary when MPTC is diagnosed after less than near-total thyroidectomy. Radioactive iodine ablation should be considered in selected patients with MPTC at increased risk of recurrence or metastatic spread.

Long-term follow-up of patients with elevated serum calcium concentrations in Swedish primary care.

OBJECTIVE: To follow up patients with elevated calcium concentrations after 10 years. DESIGN: Longitudinal, using medical records, questionnaires, and clinical investigation. SETTING: Primary care in Tibro, Sweden, 2008-2010. SUBJECTS: 127 patents with elevated calcium concentrations and 254 patients with normal calcium concentrations from the local community, attending the health care centre. MAIN OUTCOME MEASURES: Diagnoses and mortality in patients with elevated calcium concentrations in 1995-2000, compared with patients with normal calcium concentrations and the background population. RESULTS: The proportion of patients for whom no underlying cause was detected decreased from 55% at baseline to 12% at follow-up. Primary hyperparathyroidism was most common in women, 23% at baseline and 36% at follow-up, and the cancer prevalence increased from 5% to 12% in patients with elevated calcium concentration. Mortality tended to be higher in men with elevated calcium concentrations compared with men with normal calcium concentrations, and was significantly higher than in the background population (SMR 2.3, 95% CI 1.3-3.8). Cancer mortality was significantly increased in men (p = 0.039). Low calcium concentrations were also associated with higher mortality (p = 0.004), compared with patients with normal calcium concentrations. CONCLUSION: This study underscores the importance of investigating patients with increased calcium concentrations suggesting that most of these patients--88% in our study--will turn out to have an underlying disease associated with hypercalcaemia during a 10-year follow-up period. Elevated calcium concentrations had a different disease pattern in men and women, with men showing increased cancer mortality in this study.

Routine preoperative (111)In-octreotide scintigraphy in patients with medullary thyroid cancer.

BACKGROUND: Surgery is the only potential cure for patients with medullary thyroid carcinoma (MTC). Preoperative ultrasound, computed tomography and magnetic resonance imaging are not sensitive enough for detection of microscopic disease. The aim of this study was to investigate if routine preoperative (111)In-labelled (DTPA-D-Phe(1))-octreotide scintigraphy (SRS) could be used as a staging procedure in planning primary surgery in patients with MTC. METHODS: This study included patients with primary sporadic clinically overt MTC diagnosed between 1996 and 2009. All patients underwent conventional imaging of neck and thorax and SRS prior to standardised surgery. The findings on SRS were correlated to the findings on conventional imaging, histopathology and to postoperative biochemical results and survival. RESULTS: A total of 19 patients with sporadic MTC were enrolled. Median follow-up was 77(9-184) months. SRS visualised the primary tumour in 16 (84 %) patients. Fifteen (79 %) patients had locoregional lymph node metastases, but SRS detected metastatic lesions in only 8 (53 %) patients. In three patients with distant spread, SRS failed to detect metastatic lesions in two. At latest follow-up, six (32 %) patients had died, nine (47 %) patients were alive with elevated tumour markers, and four (21 %) patients were considered in complete biochemical remission. CONCLUSIONS: This study provided further evidence that SRS, compared to conventional imaging, is fairly sensitive for detection of primary MTC but not metastatic disease. Although preoperative SRS may be of prognostic value, there is no indication for its routine use as a staging procedure in planning primary surgery.

Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003-2005.

OBJECTIVES: To study hyperthyroidism in long-term iodine sufficiency (IS), as iodine supply affects its occurrence. DESIGN: Prospective descriptive study. PATIENTS: In 2003-2005, all referred cases of subclinical (SH) and overt hyperthyroidism (OH) were registered at diagnosis from a population (n = 631 239) in Gothenburg, Sweden. MEASUREMENTS: Information on age, gender, smoking, thyroid associated ophthalmopathy (TAO), thyroid hormones and TSH receptor antibodies (TRab) was collected. Incidences were calculated. SH and OH cases with Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA) were compared. In GD, TRab+ and TRab- cases and patients with (TAO+) and without TAO (TAO-) were compared. RESULTS: The total incidence (n/100 000/year) of hyperthyroidism was 27·6; OH 23·8; SH 3·8; GD 21·4; TMNG 4·3; and STA 1·8. SH was more common among TMNG (40·2%) and STA (45·7%) than in GD (5·9%). SH-GD patients were older, more often smokers and had lower TRab levels than OH-GD patients. FreeT4 and T3 levels in GD were higher than in TMNG and STA. FreeT4, T3 and TRab decreased with age in patients with GD, P < 0·0001. TRab- patients had lower T3 than TRab+ patients, P < 0·001. TRab was positively correlated to FreeT4, P < 0·0001. TAO occurred in 20% of patients with GD. TAO+ patients were younger than TAO- patients. Smokers did not have more TAO. CONCLUSION: The total incidence of hyperthyroidism was low. GD dominated with an age-related decline of thyroid hormones and TRab levels. The spectrum of hyperthyroidism in this long-term IS area may represent the future situation for countries with shorter history of IS.

Iodine Content and Distribution in Thyroid Specimens from Two Patients with Graves' Disease Pretreated with Either Propylthiouracil or Stable Iodine: Analysis Using X-Ray Fluorescence and Time-of-Flight Secondary Ion Mass Spectrometry.

Patients with Graves' disease can be medically prepared before surgery in different ways, which may have various effects on iodine stores. Thyroid specimens were collected at surgery from two patients pretreated with propylthiouracil (PTU) and stable iodine, respectively. A quantitative analysis of iodine content was performed using X-ray fluorescence (XRF) in frozen tissue and a qualitative analysis of aldehyde-fixed material with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS). Iodine concentrations were 0.9 mg/mL and 0.5 mg/mL in the thyroid tissue from the patients treated with PTU and stable iodine respectively. TOF-SIMS showed iodine in the follicle lumina in both. However, in the PTU case, iodine was also seen within the thyrocytes indicating accumulation of iodinated compounds from uninhibited hormone release. XRF and TOF-SIMS can be used to follow iodine distribution within the thyroid and the intricate processes following the different medical treatment alternatives in Graves' disease.

Prevalence of germline mutations in patients with pheochromocytoma or abdominal paraganglioma and sporadic presentation: a population-based study in Western Sweden.

BACKGROUND: Germline mutations in the susceptibility genes RET, SDHB, SDHD, and VHL have been reported in 7.5-24% of patients with pheochromocytoma (Pheo) or paraganglioma (PGL) and sporadic presentation. The purpose of the present study was to establish population-based data on the frequency of germline mutations in patients with apparently sporadic Pheo or abdominal PGL in Western Sweden. METHODS: From the Swedish National Cancer Registry, all patients with Pheo or PGL in Western Sweden (population 1.72 million) registered between 1958 and 2009 were identified (n = 256). Patients were characterized using register data, hospital records, and clinical interviews. All living patients with Pheo or abdominal PGL and sporadic presentation (n = 81) were invited to genetic screening; 71 patients accepted. Germline mutations were investigated by using direct sequencing for point mutations in RET, SDHB, SDHD, and VHL, and multiplex ligation-dependent probe amplification for gross deletions in SDHB, SDHC, SDHD, and VHL. Plasma or urinary metanephrines and/or urinary catecholamines were used for biochemical follow-up. RESULTS: The prevalence of germline mutations was 5.6%. Mutations were only seen in RET (n = 1) and SDHB (n = 3). Notably, in the patients with SDHB mutations, no malignant phenotype was observed during a mean follow-up of 23.3 years. CONCLUSIONS: The frequency of germline mutations in patients with apparently sporadic Pheo and abdominal PGL in Western Sweden was lower than in previous studies. Variations in reported frequencies of germline mutations in patients with clinically sporadic Pheo/PGL may reflect geographical differences or patient selection.

Incidence of hyperthyroidism in Sweden.

INTRODUCTION: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100,000 inhabitants per year. This extended study has evaluated the incidence for ~40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. METHODS: All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. RESULTS: A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100,000 inhabitants per year. The incidence of GD was 21.0/100,000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100,000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. CONCLUSION: The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.

Results of surgery for sporadic primary hyperparathyroidism in patients with preoperatively negative sestamibi scintigraphy and ultrasound.

PURPOSE: The purpose of this study is to investigate the results of first-time surgery for sporadic primary hyperparathyroidism (pHPT) in patients with preoperatively negative sestamibi scintigraphy and ultrasound. METHODS: Data were gathered prospectively in a multicenter database for quality control in parathyroid surgery. Between 2004 and 2008, 3,158 patients underwent first-time surgery for sporadic pHPT. A total of 984 patients were subjected to preoperative localization with ultrasound and sestamibi scintigraphy, and in 173 patients, both investigations were negative. Intraoperative findings and early outcome are reported. RESULTS: One hundred and fifty-five of 173 patients underwent bilateral neck exploration. The median weight of excised parathyroid tissue was 350 mg. In 23 patients (13.3%), the exploration was negative. A total of 112 patients (64.7%) had a histological diagnosis of parathyroid adenoma and 38 patients (22%) had multiglandular disease. Six weeks after operation, 164 patients were available for analysis, and 30 patients (18%) had persistent pHPT. The risk for persistent pHPT increased for patients with few intraoperatively identified (p = 0.001) and excised (p = 0.024) parathyroid glands. Patients operated with intraoperative parathyroid hormone (iOPTH) had lower risk for persistent pHPT 7/79 (9%) compared with 23/85 patients (27%) operated without iOPTH (p = 0.003). CONCLUSIONS: Negative localization with sestamibi and ultrasound in pHPT infers a highly selected patient population with small parathyroid adenomas, an alarmingly high rate of negative exploration, and an increased risk for persistent disease. The use of iOPTH influences cure rate favorably.