Prothrombotic changes due to an increase in thyroid hormone levels.

OBJECTIVE: With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. RESULTS: During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 µg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

[The occurrence of agranulocytosis due to antithyroid drugs in a cohort of patients with Graves disease treated with radioactive iodine 131I during 14 years]. / Výskyt agranulocytózy po tyreostaticích v kohorte pacientu s Gravesovou nemocí lécených radioaktivním jodem 131I v prubehu 14 let.

INTRODUCTION: Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit. PATIENTS AND METHODS: We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU). RESULTS: Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8). CONCLUSION: Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.

Follicular variant of papillary carcinoma presenting as a hyperfunctioning thyroid nodule.

In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.

Pneumocystis pneumonia during medicamentous treatment of Cushing's syndrome--a description of two cases.

Only a few cases of pneumocystis pneumonia (PCP) in Cushing's syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushing's syndrome. A 60-year-old woman and 20-year-old man with Cushing's syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.

Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case finding.

OBJECTIVE: Screening of thyroid disorders in pregnancy has been controversial. Recent recommendations favour targeted high-risk case finding, though this approach may miss a significant number of those affected. We aimed to assess the prevalence of accepted high-risk criteria in women with autoimmune thyroiditis and/or hypothyroidism detected from universal screening in an iodine-sufficient population. DESIGN: In 400 non-selected women in the 9-11th gestational week, thyroid-related tests were performed, and those with abnormalities were offered consultation. METHODS: TSH was determined by IRMA, and the upper cut-off value for screening was set at 3.5 mIU/l. For free thyroxine (FT(4)) and thyroperoxidase antibodies (TPO-Ab), RIAs were used, with cut-offs of <10 pmol/l and >50 IU/ml respectively. Endocrinological consultation included Doppler ultrasonography and was aimed to confirm autoimmune thyroiditis and/or hypothyroidism. The prevalence of consensus high-risk criteria was assessed. RESULTS: Among the 400 women, 65 (16.3%) had ≥1 abnormality: higher TSH was found in 10.3%, lower FT(4) in 2% and positive TPO-Ab in 8.3%. Fifty-one women were examined and followed up. Levo-T(4) treatment was initiated in 49 women for autoimmune thyroiditis (in 42), hypothyroidism (in 34) or both (in 27). Only 22 (45%) of 49 treated women fulfilled ≥1 high-risk criterion: most commonly family history (31%), history of miscarriage or preterm delivery (14%) and personal history (8%). CONCLUSIONS: Over half (55%) of pregnant women with abnormalities suggestive of autoimmune thyroiditis and/or hypothyroidism would be missed if only those with high-risk criteria were examined. A more extensive screening of thyroid autoimmunity and dysfunction seems warranted.