News Release 

Clinicians should consider screening for TSH-R-Abs before pregnancy in patients with history of autoimmune thyroid disorders

American College of Physicians

1. Clinicians should consider screening for TSH-R-Abs before pregnancy in patients with history of autoimmune thyroid disorders

Abstract: http://annals.org/aim/article/doi/10.7326/L19-0818
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Clinicians should consider screening for thyroid-stimulating hormone receptor antibodies (TSH-R-Abs) before pregnancy when the patient has a history of autoimmune thyroid disease or a history of radioactive iodine treatment or thyroidectomy. This is important because Graves' disease, an autoimmune disease caused by TSH-R-Abs, or its treatment, can lead to irreversible impairment in fetal neurodevelopment. A case report is published in Annals of Internal Medicine.

The antibodies produced in case of Graves' disease can be stimulating (TSAb), neutral, or blocking (TBAb). The net antibody activity determines the clinical phenotype. Typically, TSAbs dominate, resulting in hyperthyroidism. Rarely, TBAbs prevail, resulting in hypothyroidism. While treatment of Graves' disease dominated by TBAbs with L-T4 is straightforward, pregnancy complicates its management, as fetal hypothyroidism is a risk.

Clinicians cite the case of a 28-year-old woman with hypothyroidism caused by non-classical Graves' disease that was referred to a team at the University Hospitals Leuven in Belgium. Initially, she presented with hyperthyroidism due to a classical Graves' disease. After being treated for 36 months with high antithyroid drug doses along with L-T4 replacement to avoid hypothyroidism, she became overtly hypothyroid. TBAbs were shown to be prevailing. Two years later, she became pregnant, and the TBAbs persisted during pregnancy. Fetal development was normal with no evidence of hypothyroidism. In the postpartum period, the newborn developed transient subclinical hypothyroidism that spontaneously resolved during the next 3 months along with disappearance of maternal TSH-R-Abs. A second pregnancy followed 3 years later. The newborn developed a low normal free T4 and required treatment with L-T4 from post-natal day 18 until day 73. Both children have developed normally. The physicians caution that screening for TSH-R-Abs in such a patient is important because Graves' disease with TBAbs is rare and easy to overlook. In conclusion, this case presentation emphasizes the clinical relevance and clinical utility of measuring functional TSH-R-Ab prior, as well as during pregnancy in all patients with a history of autoimmune thyroid disease.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Brigitte Decallonne, MD, PhD, please contact sarah.cordie@uzleuven.be.

2. Interleukin-1β inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among patients with prevalent anemia

Abstract: http://annals.org/aim/article/doi/10.7326/M19-2945
Editorial: http://annals.org/aim/article/doi/10.7326/M20-0887
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Compared with placebo, interleukin-1β (IL-1β) inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among patients with prevalent anemia. A pronounced effect was seen in participants with the most anti-inflammatory response. A secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial is published in Annals of Internal Medicine.

Inflammation contributes to the development of anemia in patients with chronic disease or infection and may play a role in anemia onset in older adults. Several factors contribute to the anemia that accompanies chronic inflammation, and inflammatory cytokines, such as IL-1β and IL-6 participate in its pathogenesis. It is not clear if anti-inflammatory therapy targeting IL-1β can reverse these effects.

Researchers from Brigham and Women's Hospital, Harvard Medical School analyzed data from the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) randomized controlled trial to determine whether IL-1β inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among those with prevalent anemia. They found that IL-1β inhibition reduced the incidence of anemia by 16 percent, with a pronounced effect in participants with the most robust anti-inflammatory response. According to the authors, these hypothesis-generating data highlight the role of IL-1β /IL-6 pathway signaling in anemia onset in a large population with chronic inflammation and motivates the design of prospective confirmatory studies to identify populations that might benefit from anti-inflammatory therapies for anemia.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Paul M Ridker, MD, please contact Haley Bridger at hbridger@bwh.harvard.edu.

3. Iron chelation therapy shows clinical benefit in patients with lower risk for myelodysplastic syndromes

Abstract: http://annals.org/aim/article/doi/10.7326/M19-0916
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Iron chelation therapy with deferasirox had clinical benefit in infusion-dependent patients with lower-risk myelodysplastic syndromes (MDS). Findings from a randomized, placebo-controlled trial are published in Annals of Internal Medicine.

MDS comprise a group of disorders characterized by bone marrow failure, cytogenetic and molecular alterations, and potential for progression to acute myeloid leukemia. In patients with low risk for MDS, treatment goals primarily involve management of cytopenias, including anemia. Anemia is often treated with red blood cell transfusions that can lead to iron overload, which may have a negative impact on organs and progression to leukemia. ICT therapy for these patients has not been evaluated in randomized studies.

Researchers, including those from IRCCS Ospedale Policlinico San Martino, conducted a multicenter, randomized, double-blind, placebo-controlled trial (TELESTO) to evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with lower risk for MDS. Participants were randomly assigned to either deferasirox dispersible tablets (n=149) or matching placebo (n=76) and followed to determine EFS, or death, whichever occurred first. Median time on treatment was 1.6 years in the deferasirox group and 1.0 year in the placebo group. The researchers found that median EFS was prolonged by approximately 1 year with deferasirox versus placebo and adverse events occurred in 97.3 percent of deferasirox recipients compared to 90.8 percent in placebo recipients. Deferasirox had a clinically manageable safety profile similar to placebo, except for a non-severe, manageable increase in serum creatinine with deferasirox. However, most adverse events were likely related to the underlying disease and/or the iron overloaded state of patients. The researchers note that TELESTO is the first prospective, randomized, placebo-controlled study demonstrating clinical benefit of ICT.

Media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Emanuele Angelucci, MD, please contact Emma Houghton at emma.houghton@mudskipper.biz.

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