Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol.

Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis: The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination: Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.

Electronic reporting of rare endocrine conditions within a clinical network: results from the EuRRECa project.

Objective: The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018. Methods: Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021. Results: The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33). Conclusions: e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network. Significance statement Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.

[Treatment of Graves' disease]. / Wat is de beste aanpak voor de ziekte van Graves?

This is a commentary on a retrospective study on the pros and cons of the treatment options in new-onset Graves' hyperthyroidism, including antithyroid drugs, radioactive iodine treatment and thyroidectomy. We discuss a number of methodological concerns limiting the interpretability and clinical impact of this study. We furthermore provide a short overview of the current state of the field and knowledge gaps.

Therapeutic applications of thyroid hormone analogues.

Cellular thyroid hormone homeostasis requires adequate function of: (1) thyroid hormone transporter proteins at the plasma membrane, (2) deiodinating enzymes and (3) nuclear thyroid hormone receptors (TRs). Defects in any of these processes give rise to distinct disease entities, collectively called thyroid hormone signaling disorders. Thyroid hormone analogues hold therapeutic potential in thyroid hormone signaling disorders by bypassing defective transporters or binding to mutant TRs. This review will focus on the application of analogues in thyroid hormone signaling disorders, particularly monocarboxylate transporter (MCT)8 deficiency, and resistance to thyroid hormone due to mutations in TRß (RTHß).

The current landscape of European registries for rare endocrine conditions.

Objective To identify cross-border international registries for rare endocrine conditions that are led from Europe and to understand the extent of engagement with these registries within a network of reference centres (RCs) for rare endocrine conditions. Methods Database search of international registries and a survey of RCs in the European Reference Network for rare endocrine conditions (Endo-ERN) with an overall response rate of 82%. Results Of the 42 conditions with orphacodes currently covered within Endo-ERN, international registries exist for 32 (76%). Of 27 registries identified in the Orphanet and RD-Connect databases, Endo-ERN RCs were aware of 11 (41%). Of 21 registries identified by the RC, RD-Connect and Orphanet did not have a record of 10 (48%). Of the 29 glucose RCs, the awareness and participation rate in an international registry was highest for rare diabetes at 75 and 56% respectively. Of the 37 sex development RCs, the corresponding rates were highest for disorders of sex development at 70 and 52%. Of the 33 adrenal RCs, the rates were highest for adrenocortical tumours at 68 and 43%. Of the 43 pituitary RCs, the rates were highest for pituitary adenomas at 43 and 29%. Of the 31 genetic tumour RCs, the rates were highest for MEN1 at 26 and 9%. For the remaining conditions, awareness and participation in registries was less than 25%. Conclusion Although there is a need to develop new registries for rare endocrine conditions, there is a more immediate need to improve the awareness and participation in existing registries.

Thyroid hormone and its metabolites in relation to quality of life in patients treated for differentiated thyroid cancer.

BACKGROUND: Levothyroxine (LT4) is the standard of care in patients with hypothyroidism. Despite this replacement therapy, quality of life (QoL) remains impaired in a substantial amount of patients. The reasons for this are still a matter of debate. Suggested causes include lack of endogenous T3 secretion by the thyroid, changes in other thyroid hormone metabolites and interference by autoimmune processes. OBJECTIVE: To investigate the association between thyroid function tests (TFTs) and QoL in patients with a history of differentiated thyroid cancer on LT4 monotherapy. These patients lack endogenous thyroidal T3 secretion in the absence of autoimmune disease. MATERIALS AND METHODS: This is a cross-sectional study in 143 patients (69·2% female). Initial therapy consisted of total thyroidectomy followed by radioiodine ablation minimally one year before inclusion. We assessed health-related QoL (RAND-36), thyroid-specific QoL (ThyPRO) and fatigue with the Multidimensional Fatigue Inventory. Extensive TFTs were assessed, including 3,5-diiodo-L-thyronine (3,5-T2). RESULTS: Mean age was 50·2 years and mean time since diagnosis was 8·4 years. Median TSH was 0·042 mU/l, total T4 145·0 nmol/l, free T4 25·6 pmol/l, total T3 1·93 nmol/l, reverse T3 0·53 nmol/l and 3,5-T2 0·86 nmol/l. Multiple linear regression analyses did not show any association between QoL and the different TFTs, including T4/T3 and 3,5-T2/T3 ratios reflecting peripheral metabolism. CONCLUSION: We did not find any association between TFTs and QoL in athyreotic patients on LT4 monotherapy. Our data do not provide evidence that a slight increase in dose improves fatigue or well-being in hypothyroid patients on LT4 therapy.

[Relapsing infections with Clostridium difficile]. / Recidiverende infecties met Clostridium dificile.

Two women, aged 78 and 85 years, presented with watery diarrhoea and fever after a course of antibiotic therapy. Pseudo-membranous colitis was diagnosed, which was adequately treated. In both patients the C. difficile colitis relapsed, which was successfully treated with a pulse and tapering scheme of vancomycin. C. difficile infection is a frequent cause of antibiotic-associated diarrhoea. Clinical presentation can vary in severity. Cytotoxin testing, immunoassay and endoscopy are important tools in diagnosing C. difficile colitis. Like the first infection, the first relapse must be treated with metronidazole or vancomycin. To treat a second relapse, a pulse and tapering dose of vancomycin has been recommended. Nevertheless, multiple recurrences may occur, which are difficult to treat.

[Still no indications that the treatment of growth hormone deficient adults with growth hormones is unsafe]. / Vooralsnog geen aanwijzingen voor onveiligheid van de behandeling met groeihormoon van volwassen patiënten met groeihormoondeficiëntie.

Although more than 100,000 patients worldwide are estimated to have received growth-hormone treatment, there are still widespread doubts about the safety aspects of growth-hormone treatment of adults with growth-hormone deficiency (GHD). The available data are scarce and the follow-up time is short. The data do not suggest that growth-hormone treatment increases the incidence or regrowth of pituitary adenomas in adults with GHD. Equally there are no data which suggest that growth-hormone treatment of adults with GHD increases the incidence of cancer, provided that concentrations of the insulin-like growth factor I (IGF-I) achieved in the blood remain within the normal range for the age of that patient. No increase in diabetes mellitus has been reported following the introduction of growth-hormone treatment in adult GHD patients. Insulin sensitivity does not appear to change in GHD patients on growth-hormone treatment as long as relatively low physiological doses of growth hormone are used. Whether growth-hormone therapy in adult patients with GHD will prove safe in the long term remains to be established.