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Fighting thyrotoxicosis with therapeutic plasma exchange: A case report
Combatiendo la tirotoxicosis con recambio plasmático terapéutico: reporte de un caso
Álvaro Valverde Márquez
Corresponding author
alvarovalverdemarquez@gmail.com

Corresponding author.
, María Teresa Mories Álvarez, Heather Stacey Villanueva Alvarado, Ximena Carolina Vivas Vaca, Manuel Delgado Gómez
Endocrinology and Nutrition Department, Salamanca University Healthcare Complex, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">The patient is a 20-year-old woman with a history of Gilbert&#39;s syndrome&#46; At age 14 she had her first episode of Graves&#8211;Basedow disease&#44; which was adequately controlled with thiamazole for two years&#46; At age 18 she had her first recurrence and received antithyroid drug therapy for a year&#46; This treatment and follow-up were conducted in another medical department&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Eight months later&#44; she was admitted again with weight loss of 2<span class="elsevierStyleHsp" style=""></span>kg in two months and the following blood results&#58; TSH 0&#46;44<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;0&#46;48&#8211;4&#46;17&#41;&#44; free T4 1&#46;44<span class="elsevierStyleHsp" style=""></span>ng&#47;dl &#40;0&#46;83&#8211;1&#46;43&#41;&#44; free T3 3&#46;26<span class="elsevierStyleHsp" style=""></span>pg&#47;ml &#40;3&#8211;4&#46;7&#41;&#44; TSI 2 &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46; TPO and antithyroglobulin antibodies were positive&#46; Neck ultrasound suggested thyroiditis&#44; and no nodules were observed&#46; As it was mild subclinical hyperthyroidism&#44; a wait-and-see approach was adopted&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">After two months of monitoring&#44; the patient developed clear symptoms of hyperthyroidism with a significant increase in thyroid hormones&#58; TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;0&#46;55&#8211;4&#46;78&#41;&#44; free T4 9&#46;09<span class="elsevierStyleHsp" style=""></span>ng&#47;dl &#40;0&#46;89&#8211;1&#46;76&#41;&#44; free T3<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>pg&#47;ml &#40;2&#46;3&#8211;4&#46;2&#41;&#46; Considering the clinical and analytical situation&#44; treatment with thiamazole was reintroduced at a dose of 10<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">However&#44; seven days later the treatment was interrupted due to a persistent elevation of thyroid hormones levels&#46; Instead&#44; propylthiouracil 200<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h and propranolol 20<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h were administered&#44; with clinical improvement&#46; After 10 days with this treatment&#44; the patient went to Accident and Emergency with fever and general malaise&#44; and blood tests showed a significant increase in transaminases and lymphopenia &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; A concomitant infection was ruled out and the patient was admitted to hospital&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The propylthiouracil was discontinued and the patient was started on dexamethasone 2<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h&#44; propranolol 20<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h and cholestyramine 4<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;this last drug was later withdrawn due to poor tolerance&#44; including abdominal discomfort and nausea&#41;&#46; The patient also received her first cycle of therapeutic plasma exchange &#40;TPE&#41;&#44; with partial clinical improvement and a decrease in thyroid hormones by approximately 25&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Despite having completed four sessions of TPE with a total reduction of free T4 by 35&#46;71&#37;&#44; a significant elevation of thyroid hormones &#40;particularly free T3&#41;&#44; palpitations and heat intolerance persisted&#44; and lithium carbonate 400<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h and Lugol&#39;s iodine 0&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h were added&#46; The patient&#39;s thyroid hormone levels returned to within normal range after one week and total thyroidectomy was performed the next day&#44; without complications &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">As secondary effects of the TPE cycles&#44; only itching without skin lesions was described&#44; exclusively after first cycle&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Management</span><p id="par0040" class="elsevierStylePara elsevierViewall">Thyrotoxicosis is described as the clinical condition resulting from an excess of thyroid hormones for any reason&#46; Moreover&#44; thyroid storm is an acute&#44; life-threatening complication of hyperthyroidism which presents with multi-system involvement&#46; The main causes of thyrotoxicosis are hyperthyroidism caused by Graves&#8211;Basedow disease&#44; toxic multinodular goitre &#40;MNG&#41; and toxic adenoma&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> The medical treatment to control thyroid function includes antithyroid drugs&#44; beta blockers&#44; iodine solutions&#44; corticosteroids and cholestyramine&#44; before evaluating the possibility of definitive therapy with surgery or radioactive iodine&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The use of TPE to control thyrotoxicosis was first described in 1970 by Ashkar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> This procedure was applied in cases of toxic MNG&#44; thyrotoxicosis secondary to Graves&#8211;Basedow disease and thyrotoxicosis induced by iodine or amiodarone&#46; It was even used successfully in a case of thyrotoxicosis secondary to interferon alpha&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">TPE involves the extracorporeal filtration of blood to eliminate plasma and other substances &#40;autoantibodies&#44; immune complexes&#44; cryoglobulins&#44; endotoxins&#44; lipoproteins and free and bound thyroid hormones&#41; which play a role in pathologic immune responses&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a> It may also eliminate amiodarone and its metabolites&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> Afterwards&#44; plasma from a donor&#44; fresh frozen plasma&#44; albumin or a similar colloidal solution is administered&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> Although albumin binds thyroid hormone less avidly than thyroxine-binding globulin &#40;TBG&#41;&#44; it provides a much larger capacity for low-affinity binding&#44; which may contribute to lower free thyroid hormone levels&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Since its side effects include haemolysis&#44; allergic reaction&#44; infection&#44; coagulation disorders&#44; haemorrhage&#44; hypocalcaemia&#44; hypotension&#44; vasovagal reactions&#44; dyspnoea and seizure&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">8&#44;9</span></a> it is contraindicated in cases of haemodynamic instability&#44; active infection or increased risk of bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Areas of uncertainty</span><p id="par0060" class="elsevierStylePara elsevierViewall">Although dexamethasone and Lugol&#39;s solution particularly helped to reduce thyroid hormone levels&#44; this was not enough to effectively control thyroid function &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; TPE is not part of the general treatment for thyrotoxicosis&#44; but it is an alternative when the medical treatment is contraindicated or ineffective&#44; as a preliminary stage before the definitive treatment&#46; In general terms&#44; more than one cycle is required&#44;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">1&#8211;3</span></a> either daily or every three days&#44; until clinical improvement is observed&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> It is possible to achieve a decrease in thyroid hormones by over 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> The effect on thyrotoxicosis is temporary&#44; with an approximate duration of 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> A multicentre retrospective study analysed the results of TPE on 22 patients with thyrotoxicosis &#40;9 with Graves&#8211;Basedow disease and 13 with toxic nodules&#41;&#46; An average of four cycles of TPE were administered &#40;range&#58; 2&#8211;9 cycles&#41;&#44; and the levels of free T4 decreased by 41&#46;7&#37;&#46; Clinical improvement was observed in most cases &#40;91&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Guidelines</span><p id="par0065" class="elsevierStylePara elsevierViewall">The American Society for Apheresis recommends this procedure on patients with thyroid storm and severe symptoms if no improvement is observed after 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h of medical treatment or if there may be potentially severe effects due to the use of antithyroid drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a> Similar indications are included in the Japanese guidelines&#44; which specify acute liver failure as a side effect&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">TPE has been suggested as a safe and effective alternative when the medical treatment is contraindicated or ineffective&#44; as a previous step before total thyroidectomy&#44; in cases of multiple organ failure or when emergency surgery is required&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">17&#44;18</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions and recommendations</span><p id="par0075" class="elsevierStylePara elsevierViewall">In line with the medical literature&#44; TPE achieved a considerable reduction in free T4 in our patient&#44; which led to better hormonal control prior to surgery&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Although the American Society for Apheresis recommends this procedure with a 2C grade of evidence&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a> it should be considered an adequate therapeutic alternative&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Its effect is temporary&#44; with a decrease in the levels of hormones and TSI&#46; It improves the clinical symptoms and reduces the risk of thyrotoxicosis during surgery&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Funding</span><p id="par0090" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "identificador" => "sec0025"
          "titulo" => "Conclusions and recommendations"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Funding"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conflicts of interest"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-11-30"
    "fechaAceptado" => "2024-01-19"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1820522"
          "palabras" => array:5 [
            0 => "Thyrotoxicosis"
            1 => "Thyroid"
            2 => "Graves"
            3 => "Plasma"
            4 => "Exchange"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1820521"
          "palabras" => array:5 [
            0 => "Tirotoxicosis"
            1 => "Tiroides"
            2 => "Graves"
            3 => "Plasma"
            4 => "Recambio"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thyrotoxicosis is the clinical condition resulting from an excess of thyroid hormones for any reason&#46; The main causes are Graves&#8211;Basedow disease&#44; toxic multinodular goitre and toxic adenoma&#46; The medical treatment to control thyroid function includes antithyroid drugs&#44; beta blockers&#44; iodine solutions&#44; corticosteroids and cholestyramine&#46; Although therapeutic plasma exchange is not generally part of the therapy&#44; it is an alternative as a preliminary stage before the definitive treatment&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This procedure makes it possible to eliminate T4&#44; T3&#44; TSI&#44; cytokines and amiodarone&#46; In most cases&#44; more than one cycle is necessary&#44; either daily or every three days&#44; until clinical improvement is observed&#46; The effect on thyrotoxicosis is temporary&#44; with an approximate duration of 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This approach has been proposed as a safe and effective alternative when the medical treatment is contraindicated or not effective&#44; and when there is multiple organ failure or emergency surgery is required&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La tirotoxicosis es el estado cl&#237;nico resultado del exceso de hormonas tiroideas por cualquier causa&#46; Las principales causas son la enfermedad de Graves-Basedow&#44; el bocio multinodular t&#243;xico y el adenoma t&#243;xico&#46; El tratamiento m&#233;dico para controlar la funci&#243;n tiroidea incluye antitiroideos&#44; betabloqueadores&#44; preparaciones de yodo&#44; corticoides y colestiramina&#46; Aunque el recambio plasm&#225;tico terap&#233;utico no forma parte habitualmente de dicho tratamiento&#44; resulta otra opci&#243;n como paso previo a un tratamiento definitivo&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Dicho procedimiento permite eliminar T4&#44; T3&#44; TSI&#44; citoquinas y amiodarona&#46; Suele ser necesario m&#225;s de un ciclo&#44; diario o cada tres d&#237;as hasta que se observe una mejor&#237;a cl&#237;nica&#46; El efecto sobre la tirotoxicosis es transitorio&#44; con una duraci&#243;n aproximada de 24 a 48 horas&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se ha planteado como alternativa terap&#233;utica segura y eficaz cuando el tratamiento m&#233;dico est&#225; contraindicado o es inefectivo&#44; en presencia de fracaso multiorg&#225;nico o necesidad de cirug&#237;a de emergencia&#46;</p></span>"
      ]
    ]
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      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Day 13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dexamethasone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cholestyramine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Withdrawn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Propranolol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#8211;30&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;89&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FT3 &#40;2&#46;3&#8211;4&#46;2<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41;<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">h</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#46;84&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#62;20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#62;20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46;45&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46;99&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46;13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&#46;55&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&#46;54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;04&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">TPOAb &#40;&#60;60<span class="elsevierStyleHsp" style=""></span>kIU&#47;l&#41;<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">i</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#62;1300&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">310&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">384&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">TSI &#40;&#60;0&#46;1<span class="elsevierStyleHsp" style=""></span>U&#47;l&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">j</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Lymphocytes &#40;1&#8211;4&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">3</span>&#47;&#956;l&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;49&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;72&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;67&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;44&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;83&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;35&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;84&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Lithium &#40;1&#8211;1&#46;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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