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Article ; Online: Effects of Supra-Physiological Levothyroxine Dosages on Liver Parameters, Lipids and Lipoproteins in Healthy Volunteers: A Randomized Controlled Crossover Study.

Sjouke, Barbara / Elbers, Laura P B / van Zaane, Bregje / Kastelein, John J P / Hovingh, G Kees / Gerdes, Victor E A

2017 Volume 7, Issue 1, Page(s) 14174

Abstract: Eprotirome, a liver specific thyroid hormone agonist, was shown to induce significant increases in markers of liver injury along with a modest decrease in atherogenic lipids and lipoproteins. To get more insight into whether these effects on liver ... ...

Abstract	Eprotirome, a liver specific thyroid hormone agonist, was shown to induce significant increases in markers of liver injury along with a modest decrease in atherogenic lipids and lipoproteins. To get more insight into whether these effects on liver parameters were compound specific or the effect of mimicking thyrotoxicosis, we studied the effects of supra-physiological levothyroxine dosages on liver parameters, lipids and lipoproteins. We used data of a single-blinded, randomized controlled crossover trial. Herein, healthy volunteers received levothyroxine or no medication for 14 days. Thyroid hormone excess did not induce clinically relevant changes in liver parameters, while significant reductions in total cholesterol, low-density lipoprotein-cholesterol as well as apolipoprotein-B levels were observed in the intervention periods compared with the control periods. Supra-physiological thyroid hormone levels did not induce clinically relevant increases in markers of liver injury after 2 weeks of exposure, while it reduced total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B levels. This suggests that the effects of eprotirome on liver parameters in previous studies were either off-target and compound specific or due to drug-drug interaction at the level of the liver. The results of our study are relevant for the development of novel thyroid hormone agonists to reduce atherogenic lipoproteins.
MeSH term(s)	Adult ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Enzymes/blood ; Female ; Healthy Volunteers ; Humans ; Lipids/blood ; Lipoproteins/blood ; Liver/drug effects ; Liver/metabolism ; Male ; Thyroxine/administration & dosage ; Triiodothyronine/blood
Chemical Substances	Enzymes ; Lipids ; Lipoproteins ; Triiodothyronine (06LU7C9H1V) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2017-10-26
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-14526-2
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Article ; Online: Is catheter-related thrombosis after cardiac surgery clinically relevant?

Squizzato, Alessandro / Manfredi, Elisa / van Zaane, Bregje / Gerdes, Victor E

Internal and emergency medicine

2009 Volume 4, Issue 3, Page(s) 267–268

MeSH term(s)	Cardiac Surgical Procedures ; Catheterization, Central Venous/adverse effects ; Humans ; Postoperative Complications ; Thrombosis/etiology
Language	English
Publishing date	2009-03-19
Publishing country	Italy
Document type	Letter
ZDB-ID	2454173-4
ISSN	1970-9366 ; 1828-0447
ISSN (online)	1970-9366
ISSN	1828-0447
DOI	10.1007/s11739-009-0238-3
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Article ; Online: Arterial and venous thrombosis in endocrine diseases.

van Zaane, Bregje / Stuijver, Danka J F / Squizzato, Alessandro / Gerdes, Victor E A

Seminars in thrombosis and hemostasis

2013 Volume 39, Issue 5, Page(s) 489–495

Abstract: Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of ... ...

Abstract	Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency, pheochromocytoma, hyperparathyroidism, hyperaldosteronism, hyperprolactinemia, and growth hormone excess and deficiency; on parameters of hemostasis; and on arterial and venous thrombotic events. All these endocrine diseases do have, or may have, influence either on hemostasis or on the risk of thrombotic events. Future studies are needed to establish the clinical relevance of these associations.
MeSH term(s)	Arterial Occlusive Diseases/complications ; Endocrine System Diseases/complications ; Growth Hormone/deficiency ; Growth Hormone/metabolism ; Hemostasis ; Humans ; Hydrocortisone/deficiency ; Hydrocortisone/metabolism ; Thrombosis/complications ; Thyroid Diseases/complications ; Venous Thrombosis/complications
Chemical Substances	Growth Hormone (9002-72-6) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0033-1343889
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Article ; Online: Schildklierdiagnostiek bij dyslipidemie.

Stuijver, Danka J F / van Zaane, Bregje / Gerdes, Victor E A / Stroes, Erik S

Nederlands tijdschrift voor geneeskunde

2012 Volume 156, Issue 2, Page(s) A4301

Abstract: We describe 2 patients, a 49-year-old man presenting with dyspnoea and fatigue, and a 50-year-old woman referred for hypercholesterolaemia and hypertension. Both patients appeared to have hypothyroidism-induced dyslipidaemia. The lipid abnormalities ... ...

Title translation	Screening for thyroid dysfunction in dyslipidaemia patients.
Abstract	We describe 2 patients, a 49-year-old man presenting with dyspnoea and fatigue, and a 50-year-old woman referred for hypercholesterolaemia and hypertension. Both patients appeared to have hypothyroidism-induced dyslipidaemia. The lipid abnormalities resolved completely following thyroid hormone replacement therapy. Hypothyroidism is a well-known cause of secondary dyslipidaemia and may therefore predispose to the development of atherosclerotic disease. Measurement of thyroid hormone levels are, however, often not included in the screening of dyslipidaemia patients. The cases presented illustrate the insidious and diverse clinical presentations and diagnostic challenges of hypothyroidism. In addition, these cases demonstrate that clinical and biochemical screening for thyroid dysfunction is of paramount importance in all dyslipidaemia patients to prevent inappropriate initiation of lipid-lowering therapy.
MeSH term(s)	Diagnosis, Differential ; Diagnostic Errors ; Dyslipidemias/diagnosis ; Dyslipidemias/drug therapy ; Dyslipidemias/etiology ; Female ; Humans ; Hypolipidemic Agents/therapeutic use ; Hypothyroidism/complications ; Hypothyroidism/diagnosis ; Hypothyroidism/drug therapy ; Male ; Middle Aged ; Thyroid Hormones/therapeutic use ; Treatment Outcome
Chemical Substances	Hypolipidemic Agents ; Thyroid Hormones
Language	Dutch
Publishing date	2012
Publishing country	Netherlands
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Under-reporting of venous and arterial thrombotic events in randomized clinical trials: a meta-analysis.

Stuijver, Danka J F / Romualdi, Erica / van Zaane, Bregje / Bax, Leon / Büller, Harry R / Gerdes, Victor E A / Squizzato, Alessandro

Internal and emergency medicine

2015 Volume 10, Issue 2, Page(s) 219–246

Abstract: For the detection of unwanted outcomes of new interventions, physicians rely on adverse event reporting. We attempt to quantify the reported incidence of venous thromboembolism (VTE) and arterial thrombosis (AT) in randomized clinical trials (RCTs), and ... ...

Abstract	For the detection of unwanted outcomes of new interventions, physicians rely on adverse event reporting. We attempt to quantify the reported incidence of venous thromboembolism (VTE) and arterial thrombosis (AT) in randomized clinical trials (RCTs), and evaluate the extent of under-reporting. We selected all therapeutic RCTs published in the four highest-impact general medicine journals between January 2011 and July 2011. Patients were categorized according to VTE risk. The occurrences of VTE and AT, either as predefined outcome or adverse event, were assessed. We identified 131 RCTs. VTE and AT were not reported in 89 and 70 % of these studies, respectively. The raw-unweighted reported incidence in the 3 studies with predefined outcomes for VTE was 8.4 (7.8-9.1) per 1,000 person-years. In the 128 studies without predefined outcomes for VTE, (consisting of 322,029 individuals, including patients with cancer, inflammatory disease, cardiovascular disease, surgery, adding up to a follow-up >500,000 person-years), an incidence of 0.4 (0.4-0.5) per 1,000 person-years was found. The reported incidence of AT in 18 studies in which AT was part of predefined outcomes was 25.6 (24.9-26.3) per 1,000 person-years. In 92 studies without predefined outcomes for AT (231,638 individuals, follow-up >200,000 person-years,), the incidence was 2.5 (2.3-2.7) per 1,000 person-years. The incidence of VTE and AT in RCTs is highly under-reported. Uniform registration of adverse events, even when unlikely to be related to the intervention, is necessary to be able to inform physicians about the potential toxicities of new therapeutic strategies.
MeSH term(s)	Arteries/pathology ; Embolism/epidemiology ; Humans ; Incidence ; Randomized Controlled Trials as Topic/methods ; Randomized Controlled Trials as Topic/standards ; Research Design/standards ; Risk Factors ; Venous Thromboembolism/epidemiology
Language	English
Publishing date	2015-03
Publishing country	Italy
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2454173-4
ISSN	1970-9366 ; 1828-0447
ISSN (online)	1970-9366
ISSN	1828-0447
DOI	10.1007/s11739-014-1168-2
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Article ; Online: The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis.

Squizzato, Alessandro / Van Zaane, Bregje / Gerdes, Victor E A / Büller, Harry R

Seminars in thrombosis and hemostasis

2011 Volume 37, Issue 1, Page(s) 41–48

Abstract: Endocrine disorders can influence the hemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. The present review updates the available evidence on the influence of pituitary, adrenal, and ... ...

Abstract	Endocrine disorders can influence the hemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. The present review updates the available evidence on the influence of pituitary, adrenal, and parathyroid hormones on the coagulation and the fibrinolytic system, and their possible clinical implications. The literature supports a possible relevant clinical effect of the imbalance between coagulation and fibrinolysis on thrombotic events in endogenous Cushing's syndrome. An effect on markers of coagulation and fibrinolysis has been shown for hyperprolactinemia, growth hormone excess or deficiency, exogenous hypercortisolism, pheochromocytoma, primary hyperaldosteronism, and hyperparathyroidism. However, the clinical relevance is still unproven. Until definitive evidence is available, clinicians should be aware of the possibility that endocrine disorders may be risk factors for thrombotic events.
MeSH term(s)	Adrenal Glands/physiology ; Blood Coagulation Disorders/blood ; Endocrine System Diseases/blood ; Hemostasis ; Humans ; Parathyroid Hormone/blood ; Peptide Hormones/blood ; Pituitary Hormones/blood ; Thrombosis/blood
Chemical Substances	Parathyroid Hormone ; Peptide Hormones ; Pituitary Hormones
Language	English
Publishing date	2011-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0030-1270070
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Article ; Online: The effect of subclinical hypothyroidism on vitamin K antagonist treatment.

Squizzato, Alessandro / Galli, Luca / van Zaane, Bregje / Romualdi, Erica / Stuijver, Danka J / Dentali, Francesco / Ageno, Walter / Gerdes, Victor E A

Thrombosis research

2012 Volume 129, Issue 4, Page(s) 520–522

MeSH term(s)	Aged ; Anticoagulants/therapeutic use ; Comorbidity ; Female ; Humans ; Hypothyroidism/drug therapy ; Hypothyroidism/epidemiology ; Male ; Netherlands/epidemiology ; Prevalence ; Risk Assessment ; Risk Factors ; Thrombosis/drug therapy ; Thrombosis/epidemiology ; Treatment Outcome ; Vitamin K/antagonists & inhibitors
Chemical Substances	Anticoagulants ; Vitamin K (12001-79-5)
Language	English
Publishing date	2012-04
Publishing country	United States
Document type	Clinical Trial ; Letter
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2011.11.009
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Article: Plasma Levels of Free Thyroxine and Risk of Major Bleeding in Bariatric Surgery.

Elbers, Laura P B / Boon, Hjalmar A / Moes, Maaike I / van Zaane, Bregje / Brandjes, Dees P M / Fliers, Eric / Büller, Harry R / Cannegieter, Suzanne / Gerdes, Victor E A

European thyroid journal

2016 Volume 5, Issue 2, Page(s) 139–144

Abstract: Background: In a recent study of patients using vitamin K antagonists, those with low free thyroxin (FT4) levels within the normal range had a 3- to 5-fold increased risk of major bleeding. We tested the hypothesis that low levels of preoperative FT4 ... ...

Abstract	Background: In a recent study of patients using vitamin K antagonists, those with low free thyroxin (FT4) levels within the normal range had a 3- to 5-fold increased risk of major bleeding. We tested the hypothesis that low levels of preoperative FT4 within the reference range are associated with an increased risk of major bleeding during and after bariatric surgery. Methods: The charts of 2,872 consecutive patients undergoing bariatric surgery were retrospectively screened for bleeding episodes. Patients with major bleeding until 1 month after surgery were compared to randomly selected control patients without bleeding, in a ratio of 1:4. We evaluated the association between preoperative FT4 levels and the risk of major bleeding by logistic regression. Results: Seventy-two cases (2.5%) with major bleeding were identified and 288 controls were selected. The median plasma level of FT4 was 13 pmol/l (interquartile range: 12-14) in the cases as well as in the controls. No clear effect was observed of low levels of FT4 on the risk of major bleeding: odds ratio 1.48 (95% CI: 0.46-4.80) for patients with an FT4 level <11 pmol/l, 1.03 (0.49-2.18) for patients with an FT4 level <12 pmol/l, and 1.12 (0.65-1.94) for patients with an FT4 level <13 pmol/l as compared to patients with FT4 values greater than or equal to these cutoff levels. Interpretation: We did not observe an increased risk of major bleeding with low levels of FT4 in patients undergoing bariatric surgery.
Language	English
Publishing date	2016-06-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2659767-6
ISSN	2235-0802 ; 2235-0640
ISSN (online)	2235-0802
ISSN	2235-0640
DOI	10.1159/000446431
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Article ; Online: The Hypercoagulable state in Hyperthyroidism is mediated via the Thyroid Hormone β Receptor pathway.

Elbers, Laura P B / Moran, Carla / Gerdes, Victor Ea / van Zaane, Bregje / Meijers, Joost / Endert, Erik / Lyons, Greta / Chatterjee, V Krishna / Bisschop, Peter H / Fliers, Eric

European journal of endocrinology

2016

Abstract: Objective: Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor β (TRβ) exhibit elevated circulating thyroid ... ...

Abstract	Objective: Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor β (TRβ) exhibit elevated circulating thyroid hormones (TH) with refractoriness to TH action in TRβ-expressing tissues. We tested the hypothesis that the hypercoagulable state in hyperthyroidism is mediated via the TRβ. Design: We conducted a cross-sectional study from November 2013 to January 2015 in 3 hospitals in the Netherlands and the United Kingdom. Methods: Patients with RTH due to defective TRβ (n=18), patients with hyperthyroidism (n=16) and euthyroid subjects (n=18) were included. TH concentrations and markers of coagulation and fibrinolysis were measured. Data are expressed as median [interquartile range]. Results: Free thyroxine (FT4) levels were slightly higher in hyperthyroid patients than in RTH patients (53.9 [30.5-70.0] and 34.9 [28.4-42.2]pmol/l, respectively, P=0.042). Both groups had raised FT4 levels compared to euthyroid subjects (14.0 [13.0-15.8] pmol/l, P≤0.001). Levels of von Willebrand factor (VWF), factor (F) VIII, fibrinogen, and D-dimer were significantly higher in hyperthyroid patients than in RTH patients (VWF 231 [195-296] vs. 111 [82-140]%, FVIII 215 [192-228] vs. 145 [97-158]%, fibrinogen 3.6 [3.0-4.4] vs. 2.8 [2.5-3.2]g/L, D-dimer 0.41 [0.31-0.88] vs. 0.20 [0.17-0.26]mg/L, respectively, P≤0.001), while there were no differences between RTH patients and euthyroid controls. Conclusions: Parameters of coagulation and fibrinolysis were elevated in hyperthyroid patients compared to patients with RTH due to defective TRβ, whereas these parameters were not different between euthyroid controls and RTH patients, despite elevated FT4 concentrations in RTH patients. This indicates that the procoagulant effects observed in hyperthyroidism are mediated via the TRβ.
Language	English
Publishing date	2016-03-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1530/EJE-15-1249
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Article: Arterial and Venous Thrombosis in Endocrine Diseases

van Zaane, Bregje / Stuijver, Danka J. F. / Squizzato, Alessandro / Gerdes, Victor E. A.

Seminars in Thrombosis and Hemostasis

(Disease-Specific Thrombosis)

2013 Volume 39, Issue 05, Page(s) 489–495

Series title	Disease-Specific Thrombosis
Abstract	Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency, pheochromocytoma, hyperparathyroidism, hyperaldosteronism, hyperprolactinemia, and growth hormone excess and deficiency; on parameters of hemostasis; and on arterial and venous thrombotic events. All these endocrine diseases do have, or may have, influence either on hemostasis or on the risk of thrombotic events. Future studies are needed to establish the clinical relevance of these associations.
Keywords	thrombosis ; thyroid hormone ; cortisol ; parathyroid hormone ; aldosterone ; pheochromocytoma ; hyperprolactinemia ; growth hormone
Language	English
Publishing date	2013-04-30
Publisher	Thieme Medical Publishers
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0033-1343889
Database	Thieme publisher's database

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