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Introduction: DICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre, which is the most common manifestation among individuals carrying pathogenic DICER1 variants. This is the first study estimating the prevalence of pathogenic DICER1 variants in young individuals with multinodular goitre., Methods: Danish individuals diagnosed with nodular goitre based on thyroidectomy samples in 2001-2016 with the age limit at time of operation being ≤ 25 years were offered germline DICER1 gene testing., Results: Six of 46 individuals, 13% (CI [3.3;22.7], p <0.05), diagnosed with nodular goitre on the basis of thyroidectomy samples under the age of 25 years had pathogenic germline variants in DICER1 . They were found in different pathoanatomical nodular goitre cohorts i.e. nodular goitre (n=2), colloid nodular goitre (n=3) and hyperplastic nodular goitre (n=1)., Conclusions: We recommend referral of patients thyroidectomised due to goitre aged <21 years and patients thyroidectomised due to goitre aged <25 years with a family history of goitre to genetic counselling. Patients of all ages thyroidectomised due to goitre, who are affected by another DICER1 manifestation should be referred to genetic counselling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KT declared a past collaboration with one of the authors KW to the handling editor., (Copyright © 2021 Altaraihi, Hansen, Santoni-Rugiu, Rossing, Rasmussen, Gerdes and Wadt.)

Background: Dementia is an increasing burden to the health care system. It is currently debated whether hyperthyroidism is associated with a risk of dementia. Our aim was to determine the risk of dementia in hyperthyroid individuals and whether this was associated with duration of hyperthyroidism. Methods: Risk of dementia in hyperthyroid individuals was evaluated in two cohorts and matched reference populations. The Danish National Patient Registry (DNPR) cohort is a registry-based Danish nationwide cohort followed for a median of 7.2 years (from 1995 to 2013), whereas the OPENTHYRO registry cohort comprises 235,547 individuals who had at least one serum thyrotropin (TSH) measurement in the period from 1995 to 2011 and was followed for a median of 7.3 years. Each hyperthyroid case was matched with four controls according to age and sex using density sampling. Hyperthyroidism was defined as either an International Classification of Diseases Version 10 (ICD-10) diagnosis of toxic nodular goiter (TNG) or Graves' disease (GD), or two measurements of a TSH below 0.3 mU/L in the DNPR and OPENTHYRO registry cohort, respectively. The primary outcome was all-cause dementia, defined as either an ICD-10 code of dementia or prescription of medicine for dementia, with subgroup analyses of vascular dementia and Alzheimer's disease. Results: The DNPR cohort had 56,128 patients with hyperthyroidism, 2689 of whom were registered with dementia. The reference population had 224,512 individuals, of whom 10,199 had dementia (hazard ratio 1.17; 95% confidence interval [CI]: 1.12-1.23). Risk of dementia, whether Alzheimer's or vascular, was higher in both GD and TNG. The OPENTHYRO registry cohort constituted 2688 hyperthyroid individuals and 10,752 euthyroid control individuals of whom 190 and 473 individuals, respectively, were subsequently diagnosed with dementia (HR 1.06; 95% CI: 0.89-1.26). For each 6 months of decreased TSH, the risk of all-cause dementia was significantly higher (HR 1.16; 95% CI: 1.12-1.22). Conclusions: Using large-scale registry-based data, we found increased risk of dementia in hyperthyroid individuals. Every 6 months of decreased TSH was associated with increased risk of dementia by 16%, compared with individuals with normal TSH. Our data support early diagnosis and intervention in patients with hyperthyroidism.

Background and Objective: Hyperthyroid patients treated with radioiodine have increased morbidity and mortality from cerebrovascular events. This risk has until now has been attributed to the hyperthyroidism. However, radioiodine therapy of benign thyroid diseases exposes the carotid arteries to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity., Methods: In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated with radioiodine between 1975 and 2008 were matched 1:4 on age and sex with random controls. The cohort was followed from the date of treatment until hospitalization due to cerebrovascular event, death, 20 years of follow-up or March 2013. Data were analyzed in competing risk models adjusting for age, sex, Charlson's comorbidity score, atrial fibrillation and previous cerebrovascular events., Results: Mean follow-up time was 11.5 years, mean age 61 years, with a total number of 3228 events. Comparing all radioiodine-treated patients with controls, the fully adjusted model showed increased risk of cerebrovascular events among all treated patients, hazard ratio (HR) 1.18 (95% CI 1.09-1.29). The risk was increased among hyperthyroid (HR 1.17; 95% CI 1.07-1.28) as well as euthyroid patients (HR 1.21; 95% CI 1.02-1.44)., Conclusions: We report an increased risk of cerebrovascular events in hyperthyroid as well as euthyroid patients treated with radioiodine for benign thyroid disorders. That these patient groups have similar risks suggests the possibility that radiation from radioiodine contributes to cerebrovascular morbidity via acceleration or initiation of atherosclerosis., (© 2015 European Society of Endocrinology.)

Background: Routine measurement of serum calcitonin to detect medullary thyroid carcinoma (MTC) continues to be fiercely debated, although less attention has been paid to the positive predictive value (PPV) of this method., Methods: We collected data from 959 patients with nontoxic nodular goiter; thyroidectomy was performed in 307 of these patients., Results: Thirty-nine patients had elevated serum calcitonin; 6 of these patients had MTC detected by the initial diagnostic setup. No additional patient in the cohort was registered in the Danish Thyroid Cancer Database, reflecting that all patients with MTC were classified correctly initially. The sensitivity of serum calcitonin for detection of MTC was 100%, the specificity was 95.3%, the positive predictive value was 15.4%, and the negative predictive value was 100%., Conclusion: Serum calcitonin has high sensitivity and specificity for detection of MTC. The low PPV might lead to unnecessary thyroid surgery. Thus, the result of serum calcitonin measurement should always be interpreted in the context of other clinical variables.

Aim: To study fracture risk in patients with hyperthyroidism and hypothyroidism., Subjects and Methods: All patients with hyperthyroidism or autoimmune hypothyroidism diagnosed for the first time between 1983 and 1996 in Denmark were identified through the National Patient Discharge Register. Each patient was compared with three age- and gender-matched controls randomly selected from the general population. Fracture occurrence before and after diagnosis was compared between patients and controls., Results: 11,776 patients with hyperthyroidism (6301 patients with diffuse toxic goiter, mean age, 52.1 +/- 18.6 years, and 5475 with nodular toxic goiter, mean age, 60.4 +/- 15.9 years), and 4473 patients with hypothyroidism (mean age, 66.1 +/- 17.3) were identified. In patients with hyperthyroidism, fracture risk was only significantly increased around the time of diagnosis (incidence rate ratio [IRR] between 1.26 and 2.29), but decreased to normal levels after diagnosis. Surgical treatment of hyperthyroidism was associated with a decreased fracture risk after diagnosis (RR = 0.66, 95% confidence interval [CI]: 0.55-0.78). In hypothyroidism, fracture risk was significantly increased both before and after diagnosis with a peak around the time of diagnosis (IRR between 2.17 and 2.35)., Conclusions: Fracture risk is increased in hyperthyroidism and hypothyroidism. Thyroid surgery seems associated with a decreased fracture risk in hyperthyroid patients.