The Combination of Absent Thyroid Peroxidase Antibodies and High Thyroid-Stimulating Immunoglobulin Levels in Graves' Disease Identifies a Group at Markedly Increased Risk of Ophthalmopathy

Thyroid ◽  
1999 ◽  
Vol 9 (12) ◽  
pp. 1175-1180 ◽  
Author(s):  
D.H.C. KHOO ◽  
S.C. HO ◽  
L.L. SEAH ◽  
K.S. FONG ◽  
E.S. TAI ◽  
...  
2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A935-A936
Author(s):  
Joseph Arguinchona ◽  
Anusha Pinjala ◽  
Andrea George

Abstract Background: Cerebral venous thrombosis (CVT) accounts for <1% of strokes. In most cases, there is a predisposition to hypercoagulability; however, in about 30% of cases there is no identifiable etiology. Risk factors include pregnancy, puerperium, oral contraceptives, and coagulopathies and rarely hyperthyroidism. To the best of our knowledge there is no reported cases of CVT in uncontrolled hyperthyroidism with no underlying hypercoagulable disorder. We present a case where a woman developed CVT in the setting of uncontrolled hyperthyroidism. Clinical Case: A 24 year-old Caucasian woman was diagnosed with hyperthyroidism during 1st trimester of pregnancy based labs and was treated with propylthiouracil (PTU) 150 mg bid. At 34 weeks of pregnancy her FT4 normalized and PTU was discontinued. Three and half months post-partum she presented with left frontal headache, photophobia, phonophobia and transient visual loss on the right. Physical exam revealed right homonymous hemianopia without meningismus and an enlarged thyroid. Vitals showed BP 108/57 mm of Hg, HR 162 beats/min, RR of 23/min. CT head without contrast showed 8 mm focal hyperdensity along the left tentorium projecting at the left occipital lobe. She developed seizures after admission. MRI brain with and without contrast showed diffusely small left transverse and sigmoid sinus with a focal area of dural sinus thrombosis. MRI venogram of head confirmed CVT. She was started on levetiracetam and low dose heparin drip. Further workup showed: TSH <0.005 UIU/ml with FT4>8 ng/dl, TSH receptor antibodies 11.10 (normal range 0.00 - 1.75 IU/L), thyroid peroxidase antibody >1300 (normal range <=59 u/ml), and thyroid stimulating antibodies 6.85 (0.00 - 0.55 IU/L) suggestive of Graves disease. She was initiated on PTU 200 mg Q8hrs, propranolol 80 mg Q8hrs and lugol’s iodine 5 drops Q8hrs. Hypercoagulable workup except for protein C and S returned unremarkable. Over the next several days, thyroid levels improved significantly. She was discharged home on warfarin and methimazole. Conclusion: The exact pathophysiology of CVT in hyperthyroidism remains unclear. Some proposed mechanisms include increased activity of pro coagulative plasma constituents including Von Willebrands Factor, Factor IX, X, antithrombin, and fibrinogen as well as an increased aPTT and a decrease in thrombolytic factors like t-PA. These changes result in an increased risk of thrombosis. This case demonstrates the potential development of CVT as a result of untreated overt hyperthyroidism. It highlights the importance of treatment and close follow up of Graves’ disease to prevent severe complications. Further studies need to be done to understand the process of coagulation in hyperthyroidism and this could allow clinicians to better identify hyperthyroid patients at risk for clotting.


2019 ◽  
Vol 12 (3) ◽  
pp. 131-135
Author(s):  
Adam Grice

Subclinical hypothyroidism is a common condition associated with a raised thyroid-stimulating hormone and a normal serum free thyroxine that affects about 10% of females over 55 years in age. The most common cause is autoimmune thyroid disease, with 2.5% of patients with subclinical hypothyroidism progressing to clinically overt hypothyroidism each year. The rate of progression is higher in patients with anti-thyroid peroxidase antibodies and higher levels of thyroid-stimulating hormone. Only a small proportion of patients with subclinical hypothyroidism have symptoms, and although there is some debate in the literature about which patients should be treated, the National Institute for Health and Care Excellence clinical knowledge summaries give clear recommendations. There is an increased risk of cardiovascular disease in patients with subclinical hypothyroidism; it is uncertain whether treatment with levothyroxine reduces this risk. When deciding whether to treat subclinical hypothyroidism consider the patient’s age, symptoms, presence of anti-thyroid peroxidase antibodies, thyroid-stimulating hormone levels and risk factors such as cardiovascular disease.


Author(s):  
S. Khamisi ◽  
M. Lundqvist ◽  
P. Emadi ◽  
K. Almby ◽  
Ö. Ljunggren ◽  
...  

Abstract Purpose Serum thyroglobulin levels are often elevated in Graves’ disease (GD) and in most cases decrease during treatment. Its relation to Graves’ orbitopathy (GO) has not been clarified. Previously, a risk of GO has been linked to smoking, TSH receptor stimulation, high TSH-receptor antibodies (TRAb), low thyroid peroxidase and thyroglobulin antibodies (TPOAb, TgAb). Methods We examined Tg levels in 30 consecutive patients with GD were given drug therapy (methimazole + thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. 17 patients had GO, 11 of whom had it at diagnosis while 6 developed GO during treatment. During the study, 5 subjects were referred to radioiodine treatment, 3 to surgery. The remaining 22 subjects (GO n = 12, non-GO n = 10) completed the drug regimen. Results At diagnosis, Tg levels in GO patients (n = 11) were higher (84, 30–555 µg/L, median, range) than in non-GO patients (n = 19) (38, 3.5–287 µg/L), p = 0.042. Adding the 6 subjects who developed eye symptoms during treatment to the GO group (n = 17), yielded p = 0.001 vs. non-GO (n = 13). TRAb tended to be higher, while TPOAb and TgAb tended to be lower in the GO group. For the 22 patients who completed the drug regimen, Tg levels were higher in GO (n = 12) vs. non-GO (n = 10), p = 0.004, whereas TRAb levels did not differ. Conclusion The data may suggest that evaluation of thyroglobulin levels in GD could contribute to identify patients at increased risk of developing GO. Possibly, thyroidal release of Tg in GD reflects a disturbance that also impacts retroorbital tissues.


2020 ◽  
Vol 26 (9) ◽  
pp. 1026-1030 ◽  
Author(s):  
Christopher A. Muir ◽  
Graham R.D. Jones ◽  
Jerry R. Greenfield ◽  
Andrew Weissberger ◽  
Katherine Samaras

Objective: Graves’ disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRAbs) are clearly pathogenic, but the role of thyroidperoxidase antibodies (TPOAbs) in Graves disease is unknown. Methods: We retrospectively studied whether TPOAb positivity reduced risk of relapse following antithyroid drug (ATD) treatment in newly diagnosed Graves disease. Results: During follow-up of 204 patients with TRAb-positive Graves disease, 107 (52%) relapsed following withdrawal of ATD. Mean age was 40.0 years, and 82% were female. The average duration of ATD treatment was 23.5 months and was not different between patients who relapsed and those with sustained remission. Absence of TPOAbs significantly increased risk of Graves relapse (odds ratio, 2.21). Male sex and younger age were other factors significantly associated with increased risk of relapse. Conclusion: TPOAb positivity significantly improves the odds of remission following ATD treatment in newly diagnosed Graves’ disease. Abbreviations: ATD = antithyroid drug; CI = confidence interval; FT3 = free triiodothyronine; FT4 = free thyroxine; GD = Graves’ disease; HR = hazard ratio; IQR = interquartile range; OR = odds ratio; TPOAb = thyroid-peroxidase antibody; TRAb = thyrotropin-receptor antibody; TSH = thyroid-stimulating hormone


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Christopher Alan Muir ◽  
Jerry Richard Greenfield ◽  
Andrew Weissberger ◽  
Graham R D Jones ◽  
Katherine Samaras

Abstract Objective: Graves disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRABs) are clearly pathogenic, but the role of thyroid-peroxidase antibodies (TPOAb) in Graves disease is unknown. Design: We retrospectively studied whether TPOAb positivity reduced risk of relapse following anti-thyroid drug treatment in newly diagnosed Graves disease. Results: During follow-up of 204 patients with TRAB positive Graves disease, 107 (52%) relapsed following withdrawal of anti-thyroid medication. Mean age was 40.0 years and 82% were female. The average duration of anti-thyroid drug (ATD) treatment was 23.5 months and was not different between patients who relapsed and those with sustained remission. Absence of TPOAb significantly increased risk of Graves relapse (OR 2.21) and displayed a trend towards shorter time to relapse. Male sex and younger age were additional factors significantly associated with increased risk of relapse. Conclusion: TPO-antibody positivity significantly improves odds of remission following ATD treatment in newly diagnosed Graves disease.


Author(s):  
Sofie Bliddal ◽  
Nielsen Henriette Svarre ◽  
Aase Krogh-Rasmussen ◽  
Kolte Astrid Marie ◽  
Christiansen Ole Bjarne ◽  
...  

Author(s):  
Yi Wang ◽  
Fengjiang Sun ◽  
Ping Wu ◽  
Yichao Huang ◽  
Yi Ye ◽  
...  

Abstract Context While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear. Objective We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species. Methods This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants. Results Mean age of the participants was 26.6 ± 3.7 years, and mean gestational age was 10.3 ± 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR=0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, Ptrend =0.043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR=1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, Ptrend =0.010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate adjusted P<0.05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids. Conclusions Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM. The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.


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