Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Clinical characteristics and outcomes of patients operated for primary hyperparathyroidism at Tampere University Hospital in 2017-2018.

BACKGROUND AND OBJECTIVE: Studies on the outcomes of parathyroid surgery are scarce. The aim was to report the outcomes and to study the association between pre- and peri-operative information with the outcomes of patients operated for primary hyperparathyroidism. METHODS: This was a retrospective, descriptive study with unselected patients treated surgically for primary hyperparathyroidism from a catchment population of 704,500 in Finland. Data were acquired from the electronic hospital registers based on parathyroid surgery procedure codes between 1 January 2017 and 31 December 2018. Preoperative data, surgical data, preoperative and postoperative laboratory values, histopathological findings, and postoperative clinical data were recorded. RESULTS: During the 2-year study period, 149 patients with primary hyperparathyroidism were treated surgically with a 97% remission rate. Surgical complications included postoperative bleeding in two patients (1%) and vocal cord paralysis in one patient (0.6%). No postoperative infections were reported. Three patients (2%) developed postoperative hypoparathyroidism necessitating the use of alfacalcidol more than 1 month after surgery. Ionized calcium measured 0-1 days after surgery was not statistically significantly associated with remission or postoperative hypoparathyroidism. Serum parathyroid hormone (PTH) assessed 0-1 days postoperatively was associated with persistent disease, but not with postoperative hypoparathyroidism. The histopathological diagnosis was adenoma or hyperplasia in 112 patients (75%), atypical adenoma in 28 patients (19%), and carcinoma in five patients (3%). Patients with parathyroid carcinoma had higher preoperative ionized calcium and PTH values than those with adenoma or hyperplasia. CONCLUSIONS: Most patients who were operated due to primary hyperparathyroidism achieved normocalcemia after surgery, and the frequency of complications was low. Ionized calcium taken 0-1 days after surgery was not associated with remission of hyperparathyroidism or postoperative hypoparathyroidism. High postoperative serum PTH predicted persistent disease.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Stress hormone response to instrumented elective lumbar spine fusion surgery.

PURPOSE: To understand the systemic effect of major spine surgery, we investigated stress, anabolic and catabolic hormonal levels and their association with interleukin 6 (IL-6) in patients undergoing elective lumbar spine fusion surgery. METHODS: Blood samples were collected preoperatively, and at 1, 3, 42, 90 days postoperatively (POD) from 49 patients who underwent elective lumbar spine fusion surgery. RESULTS: Serum concentration of cortisol was below the preoperative value at POD 1 but did not differ from the baseline values thereafter. Adrenocorticotropic hormone (ACTH) decreased at PODs 1 and 3. Testosterone decreased at PODs 1 and 3 in men, and at POD 3 in women. Sex hormone-binding globulin decreased at PODs 1 and 3 in both genders. No changes were observed in free testosterone or growth hormone concentrations. Insulin-like growth factor 1 increased significantly above the preoperative level at PODs 42 and 90 in women, and at POD 42 in men. IL-6 was significantly elevated at PODs 1 and 3. Increases in IL-6 from the preoperative level to POD 1 correlated significantly with decreases of cortisol at POD 1 but not with ACTH. CONCLUSIONS: There were only short-term stress hormonal changes after elective lumbar spine fusion surgery. Cortisol changes after elective lumbar spine surgery are transient and might be partly cytokine induced and non-ACTH driven since there was association between cortisol and IL-6 but not with ACTH and IL-6.

Thyroid function test variability and cardiovascular morbidity in hyperthyroidism.

OBJECTIVE: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8-2.0). The coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) -associated hospital visits were assessed with logistic regression analyses. RESULTS: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03-1.09), male gender (OR: 2.33, 95% CI: 1.03-5.28) and fT4-CV (OR: 1.02, 95% CI: 1.01-1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14-0.61). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00-1.05). CONCLUSIONS: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs.

Gorham-Stout disease with life-threatening pleural effusion treated with a pleuro-peritoneal shunt: a case report.

Summary: Gorham-Stout disease (GSD) is a rare bone disease characterized by massive osteolysis and lymphatic proliferation. The origin of the condition is unknown, and no established treatment protocol exists. Massive pleural effusion is a frequent complication of GSD in the thoracic region. We present the case of a 23-year-old male with thoracic GSD, subsequent paraparesis, and life-threatening pleural effusion. The patient was managed by a multidisciplinary team with a good recovery. The pleural effusion was successfully treated with a pleuro-peritoneal shunt. This is the first report of the use of this mini-invasive technique in the management of pleural effusion related to GSD. Further, we present the potential role of interleukin-6 and bone resorption markers in the measurement of the disease activity. Learning points: Multidisciplinary approach is important in the management of rare and severe disorders such as Gorham-Stout disease. Pleuro-peritoneal shunting is a valuable option in the treatment of pleural effusion related to GSD. Interleukin-6 and bone resorption markers appear useful in measuring the disease activity of GSD.

Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1.

OBJECTIVE: MEN1 is associated with an increased risk of developing tumors in different endocrine organs. Neuroendocrine tumors of the thymus (TNETs) are very rare but often have an aggressive nature. We evaluated patients with MEN1 and TNET in three university hospitals in Finland. DESIGN/METHODS: We evaluated patient records of 183 MEN1-patients from three university hospitals between the years 1985-2019 with TNETs. Thymus tumor specimens were classified according to the new WHO 2021 classification of TNET. We collected data on treatments and outcomes of these patients. RESULTS: There were six patients (3.3%) with MEN1 and TNET. Five of them had the same common gene mutation occurring in Finland. They originated from common ancestors encompassing two pairs of brothers from sequential generations. The mean age at presentation of TNET was 44.7 ± 11.9 years. TNET was classified as atypical carcinoid (AC) in five out of six patients. One patient had a largely necrotic main tumor with very few mitoses and another nodule with 25 mitoses per 2 mm2, qualifying for the 2021 WHO diagnosis of large cell neuroendocrine carcinoma (LCNEC). In our patients, the 5-year survival of the TNET patients was 62.5% and 10-year survival 31.3%. CONCLUSION: In this study, TNETs were observed in one large MEN1 founder pedigree, where an anticipation-like earlier disease onset was observed in the most recent generation. TNET in MEN1 patients is an aggressive disease. The prognosis can be better by systematic screening. We also show that LCNEC can be associated with TNET in MEN1 patients.

Role of an automated screening tool for familial hypercholesterolemia in patients with premature coronary artery disease.

Background and aims: To validate an automated screening tool for patients with premature coronary artery disease (CAD) and high total cholesterol or LDL-C levels and assess if it would provide clinicians with additional support in identifying patients with Familial Hypercholesterolemia (FH). Methods: An IT-based automated screening tool based on coronary angiography data recorded in the KARDIO registry and laboratory values was validated among patients undergone coronary angiography in the Heart Hospital at Tampere University Hospital between 2007 and 2017 fulfilling the criteria of premature CAD (men <55 years and women <60 years) and history of high total cholesterol (>8 mmol/l) or LDL-cholesterol (>5 mmol/l) levels. Electronic health records were retrospectively analyzed to determine if these patients had been diagnosed with FH based on clinical features and whether genetic testing had been conducted. Results: The automated screening tool identified 0.7% (211/28295) of all patients undergone coronary angiography and revealed history of high cholesterol in 8% (211/2678) of patients with premature CAD during the study period. Fifty-one percent (107/211) of these patients fulfilled the clinical criteria for probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria.None of the patients had been diagnosed with FH based on clinical criteria before or after diagnosis of CAD. Thirteen percent of patients (n = 14) with probable/definite FH had been tested for genetic mutations of FH before or after CAD, five (36%) of them having a pathogenic FH variant. Two patients were referred to cascade screening. Conclusions: FH was underdiagnosed among the population studied. An automated screening tool in cardiac care could provide additional support for clinicians in diagnosing patients potentially having FH.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort.

PURPOSE: Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs. METHODS: The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC). RESULTS: The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival. CONCLUSIONS: NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.

Students' perceptions of interprofessional collaboration on the care of diabetes: A qualitative study.

Interprofessional education can promote healthcare professionals' competence to work in interprofessional collaboration, which is essential for the quality and safety of care. An interprofessional approach is particularly important in complex, chronic diseases like diabetes. This qualitative study evaluated changes in medical and nursing students' perceptions of interprofessional collaboration, induced by a novel interprofessional education course on diabetes care with practical elements. Data from focus-group interviews of 30 students before and after the course were analyzed by using inductive and deductive content analysis. The students' perceptions were illustrated as Elements of Collaborative Care (e.g. Quality of professional care relationship) and Elements of Interprofessional Collaboration (e.g. Importance of communication and Valuation of collaboration). The post-course interviews added one subcategory (Need of resources) to the pre-course perceptions, and there was improvement in ten areas of self-perceived competence in performing or understanding interprofessional collaboration on diabetes care. The course improved the students' self-perceived competence and confidence in interprofessional collaboration on the care of patients with diabetes, and their understanding of interprofessional collaboration changed towards a more patient-centred and holistic perspective. The findings support further implementation of IPE with practical elements in future health professionals' education.

A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. METHODS: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. RESULTS: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. CONCLUSION: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism.

OBJECTIVE: Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA. DESIGN: We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery. METHODS: Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2. RESULTS: In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma. CONCLUSIONS: The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.

Characteristics and Outcomes of 79 Patients with an Insulinoma: A Nationwide Retrospective Study in Finland.

OBJECTIVE: Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. DESIGN AND METHODS: Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. RESULTS: Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0.002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p < 0.001). Seventy-one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. CONCLUSIONS: The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.

Cardiovascular Morbidity and Mortality After Treatment of Hyperthyroidism with Either Radioactive Iodine or Thyroidectomy.

BACKGROUND: Hyperthyroid patients remain at an increased risk of cardiovascular diseases (CVDs) after restoring euthyroidism. The impact of the different treatment modalities of hyperthyroidism on future CVD risk remains unclear. The aims of this study were to assess cardiovascular morbidity and mortality in hyperthyroidism before and after treatment, and to compare the effects of two different treatment modalities: radioactive iodine (RAI) and thyroid surgery. METHODS: A comparative cohort study was conducted among 6148 hyperthyroid patients treated with either RAI or thyroidectomy and 18,432 age- and sex-matched controls. First, hospitalizations due to CVDs prior to the treatment were analyzed. Second, the hazard ratios (HR) for any new hospitalization and mortality due to CVDs after treatment were estimated among all the hyperthyroid patients compared to the age- and sex-matched controls and also in the RAI-treated patients compared to the thyroidectomy-treated patients. The results were adjusted for prevalent CVDs at the time of treatment. RESULTS: Before treatment for hyperthyroidism, hospitalizations due to all CVDs were more common in the hyperthyroid patients compared to the controls (odds ratio = 1.61 [confidence interval (CI) 1.49-1.73]). During the post-treatment follow-up, hospitalizations due to CVDs remained more frequent among the patients (HR = 1.15 [CI 1.09-1.21]), but there was no difference in CVD mortality (HR = 0.93 [CI 0.84-1.03]). Compared to the patients treated with thyroidectomy, the RAI-treated patients had a higher risk of hospitalization due to all CVDs (HR = 1.17), atrial fibrillation (HR = 1.28), as well as a higher CVD mortality rate (HR = 2.56). Yet, treatment with RAI resulting in hypothyroidism was not associated with increased CVD morbidity compared to thyroidectomy. CONCLUSIONS: Hyperthyroidism increases the risk of CVD-related hospitalization, and the risk is sustained for up to two decades after treatment with RAI or surgery. Hyperthyroid patients treated with RAI remain at a higher CVD risk compared to patients treated with thyroidectomy. Hypothyroidism during follow-up, however, predicts better cardiovascular outcomes.

Long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer.

OBJECTIVES: Thyroid hormone suppression therapy has been widely used in the treatment of thyroid cancer, but concerns have been raised about the cardiovascular risks of this treatment. The objective of this study was to evaluate long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer (DTC) and to assess the effect of TSH suppression and radioiodine (RAI) treatment on the cardiovascular outcome. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Patients (n = 901) treated for DTC between 1981 and 2002 at 2 Finnish University hospitals were compared with a randomly chosen reference group (n = 4485) matched for age, gender and the place of residence. Kaplan-Meier and Cox regression analyses were used to estimate the risk of morbidity or death due to different cardiovascular diseases (CVD) after the diagnosis of DTC. RESULTS: Morbidity due to any CVD (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.05-1.28) and due to all arrhythmias (HR 1.25, CI 1.06-1.48) and atrial fibrillation (AF) (HR 1.29, CI 1.06-1.57) was more frequent in the DTC patients than in the controls. The increased cardiovascular morbidity was confined to patients with a mean TSH level below 0.1 mU/L (HR 1.27, CI 1.03-1.58) and to those treated with RAI (HR 1.18, CI 1.05-1.31). Cardiovascular mortality, however, was lower among the patients than the controls (HR 0.73, CI 0.58-0.92), due to a lower mortality from coronary artery disease. CONCLUSIONS: Differentiated thyroid cancer patients have an increased CVD morbidity, which is mostly accountable to AF and to TSH suppression below 0.1 mU/L.