Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey.

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement: The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

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.

Mild hypercalcitoninaemia and sporadic thyroid disease.

BACKGROUND: Not operating on patients with mild hypercalcitoninaemia (MHCT) and sporadic thyroid disease carries the risk of omitting curative surgery for medullary thyroid cancer, but systematic surgery would result in unnecessary treatment of benign pathology. This study reviewed the management of MCHT and non-hereditary thyroid disease in one centre. METHODS: MCHT was defined as an increase in basal and stimulated calcitonin levels not exceeding 30 and 200 pg/ml respectively. Over 15 years, 125 patients who presented with MCHT and sporadic thyroid disease were followed. Surgery was indicated only if there were local pressure symptoms or suspicious histomorphological changes in solitary nodules. RESULTS: Fifty-five patients underwent total thyroidectomy and 18 unilateral total lobectomy. Histological examination revealed medullary microcarcinoma in six patients (two women and four men). C-cell hyperplasia was found in 54 patients (74 per cent) and 13 (18 per cent) harboured no C-cell pathology. Calcitonin levels stabilized after lobectomy and became undetectable following thyroidectomy. They normalized during follow-up in a third of patients who did not have surgery. CONCLUSION: Not all patients with MHCT and sporadic thyroid disease require surgery.

Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. AIMS AND METHODS: The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. RESULTS: A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)), FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast, QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI changes were only affected by the modality of TSH stimulation performed for RRA. From 3 to 9 months, changes of QoL scales and subscales were no longer statistically different in both groups of patients. Based on serum rhTSH-stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and 97.1%, respectively. A higher rate of persistent thyroid remnants was observed in the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical significance. CONCLUSIONS: rhTSH preserves QoL of patients undergoing RRA with similar rates of ablation success compared to hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.

Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential.

AIMS: To evaluate the reliability of desmoplasia as a reproducible morphological parameter indicating the metastatic potential of medullary thyroid carcinoma (MTC). METHODS AND RESULTS: One hundred and twenty cases of MTC of the Medical University of Vienna, Austria and 76 cases from the School of Medicine of Marseille, France were analysed for the presence of desmoplastic stroma reaction by four endocrine pathologists. Intra- and interobserver concordance was assessed. The Austrian cases were also analysed for various morphological parameters. Intra- and interobserver concordance were highly significant with a kappa value of 0.883 for intra-observer reliability and 0.837, 0.79 and 0.758, respectively, when pathologists N.N., C.D.M. and K.W.S. reviewed the Austrian cases. The cases from France were reviewed by C.D.M. and K.K. with a kappa value of 0.759. None of the cases that were categorized as desmoplasia negative by any of the investigators showed lymph node metastasis. No other distinct morphological characteristics could be assigned to the MTCs without desmoplasia. CONCLUSIONS: Our data indicate desmoplasia to be a reliable and highly reproducible parameter with regard to lymph node metastatic potential.

[The diagnosis and surgical treatment of neck tumors]. / Diagnostika i khirurgicheskoe lechenie opukholei shei.

On the basis of the analysis of the results of diagnosis and treatment of 319 patients with a tumour of the neck, sequence of the use of a complex of diagnostic methods, including puncture biopsy, has been substantiated. The results of subsequent histologic and cytologic study of a biopsy specimen in 89% of the patients coincided with the findings of a postoperative histologic study of the tissue removed.