Treatment of solitary thyroid nodules according to size, preoperative fine-needle aspiration cytology and frozen section: a retrospective single centre study.

Background: In order to avoid unnecessary thyroidectomies, it is important to predict the nature of thyroid nodules the more accurately possible. The size of the nodule as a predictive factor for malignancy is very controversial. Another point of debate is the accuracy of preoperative fine-needle aspiration cytology (FNAC) and frozen section (FS). The aim of our study is to correlate the nodule size with the final histological diagnosis and to estimate the accuracy of preoperative FNAC and FS. Methods: Retrospective study including 387 operated patients with ultrasound-detected solitary thyroid nodules from 01 January 2001 to 31 December 2013. The following data were collected: patient age and sex, nodule size, FNAC, FS and final histology results. Results: The odds ratio for malignancy within nodules <40 mm was 2.12 (95% CI: 1.104-4.084). The specificity of FNAC was 97.78% and the negative predictive value (NPV) was 97.78% for nodules ≥40 mm and 93.2% and 96.5% for nodules <40 mm, respectively. The observed specificity and NPV of FS ranged from 98% to 100% and from 87.4% to 98%, respectively. When combining FNAC and FS, the specificity and the NPV were 99% and 98%, respectively. Conclusions: The nodule size is not a predictive factor for thyroid cancer and therefore nodules ≥40 mm should not be routinely resected. A lege artis preparation and performance of FNAC along with an expertise on cytological interpretation can considerably diminish false-negative rate. FS can offer additional accuracy on FNAC results and should, therefore, be a part of patient treatment.

Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism?

OBJECTIVE: The effects of endogenous subclinical hyperthyroidism (eSCH) on heart and bone have been well documented. There are only limited data available regarding the impact of eSCH on weight regulation and lipid metabolism. Our aim was to evaluate the changes in body weight and metabolic parameters after total thyroidectomy in patients with pre-operative eSCH compared with pre-operative patients with euthyroid (EUT). DESIGN: A retrospective study of 505 patients who underwent total thyroidectomy for benign multinodular goitre in an academic hospital in Brussels (Belgium) was performed. PATIENT'S MEASUREMENTS: Two hundred and 25 patients were included (eSCH group: n = 74; EUT group: n = 151). The mean follow-up time was 26·1 ± 0·8 months and was similar in both groups. RESULTS: Absolute BMI gain was significantly greater in the eSCH group than in the EUT group (1·11 ± 0·17 vs 0·33 ± 0·13 kg/m2 ; P = 0·003). A significant increase in LDL cholesterol was observed in the eSCH group (16·1 ± 3·8 mg/dl; P < 0·001) but not in the EUT group (0·0 ± 3·0 mg/dl; P = 0·88). In a multivariate model, pre-operative TSH levels were the main factor significantly associated with increases in BMI or LDL cholesterol. Post-operative median TSH levels and L-thyroxine substitution were similar in both groups. CONCLUSION: After total thyroidectomy, increases in weight and serum cholesterol were observed in the eSCH group. Given that post-operative TSH levels were similar in the two groups, these observations are probably due to the correction of eSCH, suggesting a direct effect of eSCH on body weight regulation and lipid metabolism.

Thyroid lobectomy is an effective option for unilateral benign nodular disease.

OBJECTIVE: The use of thyroid lobectomy in the treatment of unilateral, benign nodules is limited by the potential of nodular recurrence in the remaining lobe. This study aimed to assess the rate and clinical impact of nodular recurrence in the contralateral lobe after thyroid lobectomy and to identify predictive factors of recurrence. DESIGN: Single-centre retrospective study. PATIENTS: Records of patients that underwent lobectomy for unilateral thyroid nodules between 1991 and 2010 were reviewed and 270 patients were included. Exclusion criteria were: presence of contralateral nodule(s) ≥5 mm on preoperative ultrasound, diagnosis of cancer necessitating completion thyroidectomy or pseudonodules. Recurrence was defined as the occurrence of nodule(s) ≥5 mm in the remaining lobe on at least one postoperative ultrasound. A set of clinical, imaging, histological and biochemical parameters was tested as predictors of recurrence using logistic regression. RESULTS: After a median follow-up of 78 months (range, 12-277 months), the global recurrence rate was 42% and recurrence of nodules of a size ≥1 cm occurred in 19%. Reoperation rate was 1·1%. 90% of patients were treated postoperatively by levothyroxine. Median time to nodular recurrence was 4 years. Preoperative contralateral lobe volume and resected thyroid weight were identified as significant predictors of recurrence (P = 0·045 and P = 0·03 respectively). CONCLUSIONS: Thyroid lobectomy is an effective therapeutic strategy for unilateral, benign nodules, resulting in a low rate of clinically relevant nodular relapse in a mildly iodine-deficient area. Patients with uninodular disease and a contralateral lobe of normal size are particularly good candidates for lobectomy.

Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients.

CONTEXT: Prolactinoma is the most frequent pituitary tumour among women of child-bearing age. Only a few studies have addressed the outcome of prolactinoma after pregnancy. OBJECTIVE: To study remission, defined as prolactin normalization without medical treatment, after pregnancy and lactation in women with prolactinoma. PATIENTS AND METHODS: A retrospective study conducted in 2 Belgian academic centres including 73 patients (54 microprolactinomas and 19 macroprolactinomas) with 104 pregnancies continuing beyond first trimester. Dopamine agonists were stopped in early pregnancy in all treated cases. Prolactin level and adenoma size at pituitary magnetic resonance imaging (MRI) were recorded before pregnancy and throughout follow-up. RESULTS: Thirty of 73 women (41%) were in remission after a median follow-up of 22 months after delivery or cessation of lactation. Adenoma size at diagnosis was smaller in women in remission (5 vs 8 mm). There was a nonsignificant higher rate of remission for microprolactinomas than for macroprolactinoma (46% vs 26%). The first pituitary MRI after pregnancy and lactation showed no tumour and a decreased adenoma size in 23% and 39% of women, respectively. MRI normalization was associated with remission. The number of pregnancies per woman as well as breastfeeding and its duration did not influence remission rate. CONCLUSION: More than 40% of women with previous diagnosis of prolactinoma have normal PRL level without medical treatment for a median follow-up of 22 months after pregnancy and lactation. The likelihood of remission is associated with a smaller initial adenoma size and normalization of pituitary MRI after pregnancy.

Thyroid function monitoring during pregnancy in euthyroid women with thyroid autoimmunity.

BACKGROUND: Thyroid autoimmunity (TAI) may be present in 1-17% of pregnant women. Monitoring of thyroid function in euthyroid pregnant women positive for anti thyroperoxidase antibodies (TPOAb +) is recommended. OBJECTIVE: To determine the prevalence and possible clinical and biological risk factors of biochemical progression (rise in serum TSH> 2.5 mU/L) at second blood sampling during pregnancy, in euthyroid women (TSH ≤ 2.5 mU/L) according to their TPOAb status. METHODS: This study included demographic and biological data from two previously published cohorts (n=274 women from August 1996 to May 1997 Copenhagen cohort, and n=66 women from January 2013 to December 2014 Brussels cohort) having at least two measurements of TSH and free thyroxine (FT4) and at least one of TPOAb during spontaneously achieved singleton pregnancies. RESULTS: The majority of women studied did not show biochemical progression. Only 4.2% progressed, significantly more frequently among TPOAb + women, as compared to TPOAb - group (9.4% vs 2.7%, p=0.015). No rise in serum TSH > 4 mU/L at 2nd sampling was observed. Higher baseline TSH levels were associated with biochemical progression in both TPOAb+ (p=0.05) and TPOAb - women (p<0.001), whereas maternal age, BMI, multiparity, smoking, FT4 and TPOAb concentrations were not significantly different between women with and without progression. CONCLUSIONS: Only a minority of euthyroid women with thyroid autoimmunity presented biochemical progression and none with a TSH > 4mU/L. Larger studies are needed to better target the subset of women that would benefit most from repeated thyroid function monitoring during pregnancy.

Thyrotropin (TSH) and thyroid autoimmunity are predictive factors for the incidental discovery of papillary thyroid microcarcinoma during thyroidectomy.

PURPOSE: To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions. METHODS: Cross sectional, single center study, involving all consecutive patients (N = 3015) who were submitted to thyroid surgery between 2001-2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed. RESULTS: No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99-2.28) and certain (OR: 1.74, 95% CI: 1.09-2.78) thyroid autoimmunity (p = 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08-1.45, p = 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24-0.67, p < 0.001). The most frequent genetic alteration was BRAFV600E mutation, found in 56.3% of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAFV600E mutation was observed. CONCLUSIONS: Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression.

Autonomously functioning thyroid nodules present intermediate malignancy risk according to European Thyroid Imaging Reporting and Data System (EU-TIRADS) and yield indeterminate cytology results.

Objectives: The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients. Methods: A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 - scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis. Results: More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03-0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1-35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12). Conclusions: Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

PAI-BEL: a Belgian multicentre survey of primary adrenal insufficiency.

Objective: Primary adrenal insufficiency (PAI) is a rare disease with an increasing prevalence, which may be complicated by life-threatening adrenal crisis (AC). Good quality epidemiological data remain scarce. We performed a Belgian survey to describe the aetiology, clinical characteristics, treatment regimens, comorbidities and frequency of AC in PAI. Methods: A nationwide multicentre study involving 10 major university hospitals in Belgium collected data from adult patients with known PAI. Results: Two hundred patients were included in this survey. The median age at diagnosis was 38 years (IQR 25-48) with a higher female prevalence (F/M sex ratio = 1.53). The median disease duration was 13 years (IQR 7-25). Autoimmune disease was the most common aetiology (62.5%) followed by bilateral adrenalectomy (23.5%) and genetic variations (8.5%). The majority (96%) of patients were treated with hydrocortisone at a mean daily dose of 24.5 ± 7.0 mg, whereas 87.5% of patients also received fludrocortisone. About one-third of patients experienced one or more AC over the follow-up period, giving an incidence of 3.2 crises per 100 patient-years. There was no association between the incidence of AC and the maintenance dose of hydrocortisone. As high as 27.5% of patients were hypertensive, 17.5% had diabetes and 17.5% had a diagnosis of osteoporosis. Conclusion: This study provides the first information on the management of PAI in large clinical centres in Belgium, showing an increased frequency of postsurgical PAI, a nearly normal prevalence of several comorbidities and an overall good quality of care with a low incidence of adrenal crises, compared with data from other registries.

18F-Fluorocholine PET/CT Is More Sensitive Than 11C-Methionine PET/CT for the Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism.

Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of 18F-fluorocholine (18F-FCH) PET/CT compared with 11C-methionine (11C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive 99mTc-sestaMIBI (99mTc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive 99mTc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by 11C-MET and 18F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. 18F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for 11C-MET PET/CT. 18F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with 11C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, 18F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by 11C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for 18F-FCH and 60% and 94%, respectively, for 11C-MET (P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for 18F-FCH and 52% and 94%, respectively, for 11C-MET (P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive 99mTc-MIBI SPECT findings, 18F-FCH PET/CT performs better than 11C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients.

SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules : What is the role of functional imaging and isotopic treatment?

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the role of thyroid scintigraphy in the diagnosis of autonomous thyroid nodules, nuclear medicine in nodules with indeterminate cytology and iodine treatment for autonomous thyroid nodules.

Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey.

BACKGROUND: Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available. METHOD: Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys. RESULTS: Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms. CONCLUSIONS: LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit.

Seasons but not ethnicity influence urinary iodine concentrations in Belgian adults.

BACKGROUND: Mild iodine deficiency (MID) is endemic in Belgium. Previous surveys, which assessed iodine nutrition in Belgium, focused on children. The iodine status of adults and the influence of ethnicity or seasonality on urinary iodine concentrations (UIC) have not been investigated. Since the nutritional profile of children differs from that of adults, we may anticipate similar differences in iodine status. Seasonal fluctuations in UIC have also been reported from other MID regions. AIM OF THE STUDY: We aimed at assessing iodine status and its association with ethnicity and seasonality in adults. METHODS: A stratified random sample of 401 healthy subjects aged between 40 and 60 years, of Belgian, Moroccan, Turkish and Congolese descent residing in Brussels was obtained. Iodine status and thyroid function were determined. RESULTS: Median UIC was 68 µg/L. The frequency of UIC below 100 µg/L was 73.3%, of which 41.9% fell between 50 and 99 µg/L, and 29.8% between 49 and 20 µg/L. There was no difference in UIC and thyroid function between subjects of different ethnic origins. The frequency of UIC below 50 µg/L was higher in the fall-winter compared to spring-summer periods (P = 0.004). Serum FT3 concentrations, but not FT4 and TSH, were significantly greater in winter than in summer. CONCLUSION: Seasonal fluctuations in UIC suggest that the risk of iodine deficiency among adults living in Brussels is higher in fall-winter than in spring-summer. The prevalence of MID in Brussels is high among adults but ethnicity does not appear to influence iodine status.

Two-day low-dose dexamethasone suppression test more accurate than overnight 1-mg in women taking oral contraceptives.

INTRODUCTION: Late-night salivary cortisol (LSaC) and 24-h urinary free cortisol measurement, and overnight 1-mg dexamethasone suppression test (1 mg-DST) are the first-line screening tests recommended for Cushing's syndrome. Through elevations in the level of cortisol-binding globulin, oral contraceptive agents lead to increases in the total plasma cortisol concentration, yielding false-positive 1 mg-DST results. OBJECTIVE: To compare the accuracy of the overnight 1-mg DST and two-day low-dose DST (2d-DST) in female volunteers taking combined oestrogen-progestin oral contraceptives (COCs). METHODS: This prospective study enrolled 30 healthy participants. Their plasma cortisol response levels were compared after the 1-mg DST and 2d-DST and classified into three categories: normal (≤50 nmol/L), doubtful (51-138 nmol/L) and abnormal (>138 nmol/L). Salivary cortisol was also measured at late night and after the DSTs. RESULTS: Following the 1-mg DST and 2d-DST, the plasma cortisol concentrations decreased to a median of 69 nmol/L and 37 nmol/L, respectively (p < 0.001). A statistically significant higher proportion of unclear or abnormal results were observed after the 1-mg DST (63%) than after the 2d-DST (27%) (p = 0.004). None of the values were >138 nmol/L after the 2d-DST, while 11% of them were abnormal after the 1-mg DST (p = 0.25). No LSaC value was abnormal. CONCLUSION: Our results suggest that, when late-night salivary cortisol is not available, the 2d-DST could be a better screening option than the 1-mg DST for women taking oral contraceptive agents who are reluctant to stop them. This finding requires confirmation in those with a suspicion of hypercortisolism.

Iron Deficiency Is a Risk Factor for Thyroid Dysfunction During Pregnancy: A Population-Based Study in Belgium.

Background: Iron deficiency affects thyroid hormone synthesis by impairing the activity of the heme-dependent thyroid peroxidase. The prevalence of iron deficiency is elevated particularly in pregnant women. This study aimed to investigate the effects of iron status on thyroid function in a nationally representative sample of mildly iodine-deficient pregnant women. Methods: The study population comprised a sample of pregnant women in Belgium during the first and third trimesters of pregnancy (n = 1241). Women were selected according to a multistage proportional-to-size stratified and clustered sampling design. Urine and blood samples were collected, and a questionnaire was completed face to face with the study nurse. Concentrations of free thyroxine (fT4), total thyroxine (T4), free triiodothyronine, thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibodies, Tg antibodies, hemoglobin, serum ferritin (SF), soluble transferrin receptor, urinary iodine concentrations (UICs) were measured and body iron stores (BIS) were calculated. Results: Median UICs were 117 and 132 µg/L in the first and third trimesters of pregnancy, respectively (p < 0.05). The frequency of SF <15 µg/L was 6.2% in the first trimester and 39.6% in the third trimester of pregnancy (p < 0.05). UIC was a significant predictor of serum Tg concentrations (p < 0.01) but not of thyroid hormone or TSH concentrations. The frequency of fT4

Metabolic Changes after Radioiodine Correction of Grade 1 and Grade 2 Subclinical Hyperthyroidism.

OBJECTIVE: Endogenous subclinical hyperthyroidism (eSCH) is defined by subnormal serum thyroid-stimulating hormone (TSH) level. There is limited evidence of metabolic changes induced by eSCH. The aim of our work was to evaluate changes in BMI and lipid parameters after radioiodine treatment in patients with grade 1 (TSH: 0.1-0.39 mlU/L) and 2 (TSH <0.1 mlU/L) eSCH. DESIGN: A retrospective study was performed on 74 patients with eSCH caused by benign autonomous nodular goiter which was treated with radioiodine. METHODS: We assessed BMI, lipids parameters, and TSH after radioiodine therapy. The 12-month follow-up time point was used to compare the primary outcome variables. TSH was measured by the electrochemiluminescence method. RESULTS: After radioiodine therapy, the absolute and relative increases in BMI at 12 months were significantly higher in the grade 2 group than in the grade 1 group (1.07 ± 0.27 kg/m2 vs. 0.26 ± 0.15 kg/m2, respectively; p = 0.023 and 4.01 ± 0.98% vs. 1.01 ± 0.56%, respectively; p = 0.026). Compared to baseline, significant increases in the levels of total cholesterol and LDL were observed after treatment in the grade 2 eSCH group (16.7 ± 4.5 mg/dL p < 0.01 and 14.3 ± 4.1 mg/dL p < 0.01, respectively) but not in the grade 1 group. In a multivariate model, a negative correlation was observed between pretreatment TSH levels and absolute BMI gain (p < 0.01). CONCLUSIONS: After correction of eSCH, increases in BMI and LDL levels were observed only in patients with grade 2 eSCH. Pretreatment serum TSH was the main independent factor associated with BMI changes after radioiodine treatment.

Etomidate infusion at low doses is an effective and safe treatment for severe Cushing's syndrome outside intensive care.

INTRODUCTION: Intravenous etomidate infusion is effective to rapidly lower cortisol levels in severe Cushing's syndrome (CS) in the intensive care unit (ICU). Recently, etomidate treatment has also been proposed at lower doses in non-ICU wards, but it is not yet clear how this approach compares to ICU treatment. METHODS: We compared data from patients with severe CS treated with high starting doses of etomidate (median: 0.30 mg/kg BW/day) in ICU or with lower starting doses (median: 0.025 mg/kg BW/day) in non-ICU medical wards. RESULTS: Fourteen patients were included, among which ten were treated with low starting doses (LD) and four with high starting doses etomidate (HD). All patients had severe and complicated CS related to adrenal carcinoma (n = 8) or ectopic ACTH secretion (n = 6). Etomidate was effective in reducing cortisol levels below 500 nmol/L in a median of 1 day in the HD group compared to 3 days in the LD group (P = 0.013). However, all patients of the HD group had etomidate-induced cortisol insufficiency and needed frequent monitoring, while no patient from the LD group required hydrocortisone supplementation. No patient in either group died from complications of CS or etomidate treatment, but final outcome was poor as six patients in the LD group and all four patients in the HD group died from their cancer during follow-up. CONCLUSION: Our study suggests that, for patients with severe CS who do not require intensive organ-supporting therapy, the use of very low doses of etomidate in medical wards should be considered.

Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions.

CONTEXT: Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult. OBJECTIVE: The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions. DESIGNS AND METHODS: We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology. RESULTS: Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)). CONCLUSION: We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin.

Dissecting the Role of Thyrotropin in the DNA Damage Response in Human Thyrocytes after 131I, γ Radiation and H2O2.

BACKGROUND: The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes. METHODS: Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (ß radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response. RESULTS: Overall, the thyrocyte responses following exposure to ß or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. ß and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to ß/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure. CONCLUSIONS: TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.