Scientific Letter
T3-predominant Graves’ disease in paediatric patients
Enfermedad de Graves con predominio de T3 en la edad pediátrica
M. Martín-Frías
, P. Enes, M.B. Roldan, M. Alonso, R. Barrio
Corresponding author
Unidad de Endocrinología Pediátrica, Servicio de Pediatría, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
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Martín-Frías, P. Enes, M.B. Roldan, M. Alonso, R. Barrio" "autores" => array:5 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Martín-Frías" "email" => array:2 [ 0 => "mmartinf.hrc@salud.madrid.org" 1 => "maria.martin.sg@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Enes" ] 2 => array:2 [ "nombre" => "M.B." "apellidos" => "Roldan" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Alonso" ] 4 => array:2 [ "nombre" => "R." "apellidos" => "Barrio" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Endocrinología Pediátrica, Servicio de Pediatría, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad de Graves con predominio de T3 en la edad pediátrica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Graves’ disease (GD) is uncommon in the paediatric age group. In these patients, the course of the disease tends to be more severe, with a lesser frequency of remissions and a greater number of relapses.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,2</span></a> The initial diagnosis is usually made based on clinical manifestations and later confirmed by the detection of decreased thyroid-stimulating hormone (TSH) levels and high serum levels of free thyroxine (fT4) and free triiodothyronine (fT3) associated with the presence of thyroid-stimulating immunoglobulin (TSI). The first-line treatment consists of the administration of antithyroid drugs. A form of GD known as triiodothyronine-predominant GD (T3-P-GD) has been described in the literature. It is characterised by sustained high levels of fT3 with normal or low levels of fT4 during part of the treatment and the followup.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a> This form, described in up to 10% of adult patients, is associated with a more severe course of disease and a poorer response to treatment. Its pathogenesis is not well understood, although type 1 and 2 deionidases, which catalyse the conversion of T4 to T3 and increase intracellular levels of T3, are known to be overexpressed in the thyroid tissues of these patients.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,5</span></a> T3-P-GD had not been described in the paediatric population until the recent publication of the data of a French cohort of 60 paediatric patients with GD in which the T3-predominant pattern was identified in 13% of the patients. These patients had more severe forms of disease, were diagnosed earlier, and required higher doses of antithyroid drugs to control their disease.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In our experience, in a cohort of 20 paediatric patients with GD in which we analysed the clinical data at the time of diagnosis, the levels of TSH, fT3 (normal range [NR] 1.7–4.53<span class="elsevierStyleHsp" style=""></span>pg/mL), fT4 (NR 0.7–1.48<span class="elsevierStyleHsp" style=""></span>ng/dL), and the fT4:fT3 ratio, as well as their clinical outcomes in relation to the treatment received, T3-P-GD was identified in three patients that exhibited clinical and laboratory patterns similar to those described in the case series published by Harvengt et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> All patients in the cohort received pharmacological treatment with thionamide-derived antithyroid drugs. The overall mean age at diagnosis of GD was 12.5 years (8.5–15.1), and 75% of the patients were female. Remission occurred in 12/20 patients (60%) after a mean 41.5 months of treatment (18–58.7), and relapses in 5/12 (42%). Of all the patients, three (15%) had transient fT3 predominance over fT4 after initiation of treatment, with the pattern lasting between one and four months. The data for these patients showed that they have higher levels of fT4 and fT3 at diagnosis, and a tendency to be diagnosed at earlier ages, have a higher prevalence of eye disease, and require higher doses of antithyroid medication to control their GD (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). We did not find any differences in the levels of TSI between both groups.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Triiodothyronine-predominant GD also occurs in the paediatric age group. In these patients, GD tends to have an earlier onset, a more severe course and a poorer response to treatment. Our experience is based on a small number of cases, but nevertheless we believe that it is important to identify these patients as soon as they are diagnosed by the serial measurement of not only fT4, but also fT3 levels. A better hormonal and molecular characterisation of these patients (study of type 1 and type 2 iodothyronine deiodinases DIO1, DIO2) could be significant in the diagnosis of this subset of patients and in determining the best therapeutic approach.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Martín-Frías M, Enes P, Roldan MB, Alonso M, Barrio R. Enfermedad de Graves con predominio de T3 en la edad pediátrica. An Pediatr (Barc). 2016;84:119–120.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Data expressed as percentage, median and interquartile range (<span class="elsevierStyleItalic">Q</span>1–<span class="elsevierStyleItalic">Q</span>3).</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Dx, diagnosis; F, female; fT3 predominance, presence of elevated fT3 with normalisation of fT4 during treatment with antithyroid drugs; fT3, (free T3) normal range, 1.7–4.53<span class="elsevierStyleHsp" style=""></span>pg/mL; fT4, (free T4) normal range, 0.7–1.48<span class="elsevierStyleHsp" style=""></span>ng/dL.</p>" "tablatextoimagen" => array:1 [ 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="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">No fT3 predominance <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">fT3 predominance</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.2 (8.6–15.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.9 (5.3–14.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex (F, %) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 (12/17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (3/3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">fT4 Dx (ng/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.4 (1.7–3.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0 (1.9–4.2)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">fT3 Dx (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.6 (6.4–16.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.9 (8.7–16.1)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">fT4:fT3 ratio at diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.23 (0.17–0.42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.21 (0.15–0.24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Goitre \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88% (15/17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100% (3/3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eye disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30% (5/17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67% (2/3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Laboratory tests showing T3-predominant pattern</td><td class="td" title="table-entry " rowspan="2" align="char" valign="top"></td><td class="td" title="table-entry " align="char" valign="top">fT4 (ng/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">fT3 (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="char" valign="top"><span class="elsevierStyleBold">Treatment and followup</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dosage (mg/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 (0.22–0.61) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 (0.16–0.70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 (15.5–57.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (11–115) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">115 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Remission (yes, %) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Relapse (yes, %) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 (4/11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (1/1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I-131 (yes, %) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab982527.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Statistical significance: <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical, laboratory and follow-up characteristics of the patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thyrotoxicosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 18 | 10 | 28 |
| 2024 October | 66 | 43 | 109 |
| 2024 September | 71 | 40 | 111 |
| 2024 August | 74 | 54 | 128 |
| 2024 July | 56 | 30 | 86 |
| 2024 June | 74 | 42 | 116 |
| 2024 May | 56 | 45 | 101 |
| 2024 April | 56 | 33 | 89 |
| 2024 March | 42 | 28 | 70 |
| 2024 February | 47 | 29 | 76 |
| 2024 January | 45 | 22 | 67 |
| 2023 December | 43 | 19 | 62 |
| 2023 November | 50 | 34 | 84 |
| 2023 October | 49 | 26 | 75 |
| 2023 September | 27 | 28 | 55 |
| 2023 August | 44 | 19 | 63 |
| 2023 July | 48 | 25 | 73 |
| 2023 June | 39 | 32 | 71 |
| 2023 May | 51 | 29 | 80 |
| 2023 April | 47 | 21 | 68 |
| 2023 March | 39 | 20 | 59 |
| 2023 February | 55 | 8 | 63 |
| 2023 January | 36 | 26 | 62 |
| 2022 December | 64 | 30 | 94 |
| 2022 November | 71 | 42 | 113 |
| 2022 October | 74 | 35 | 109 |
| 2022 September | 40 | 50 | 90 |
| 2022 August | 69 | 51 | 120 |
| 2022 July | 37 | 54 | 91 |
| 2022 June | 43 | 30 | 73 |
| 2022 May | 44 | 35 | 79 |
| 2022 April | 77 | 43 | 120 |
| 2022 March | 93 | 48 | 141 |
| 2022 February | 102 | 26 | 128 |
| 2022 January | 51 | 33 | 84 |
| 2021 December | 52 | 40 | 92 |
| 2021 November | 66 | 54 | 120 |
| 2021 October | 51 | 55 | 106 |
| 2021 September | 37 | 31 | 68 |
| 2021 August | 28 | 32 | 60 |
| 2021 July | 32 | 45 | 77 |
| 2021 June | 33 | 33 | 66 |
| 2021 May | 48 | 29 | 77 |
| 2021 April | 132 | 91 | 223 |
| 2021 March | 47 | 31 | 78 |
| 2021 February | 30 | 21 | 51 |
| 2021 January | 32 | 21 | 53 |
| 2020 December | 38 | 25 | 63 |
| 2020 November | 34 | 19 | 53 |
| 2020 October | 25 | 21 | 46 |
| 2020 September | 24 | 27 | 51 |
| 2020 August | 26 | 16 | 42 |
| 2020 July | 20 | 17 | 37 |
| 2020 June | 15 | 6 | 21 |
| 2020 May | 40 | 23 | 63 |
| 2020 April | 26 | 10 | 36 |
| 2020 March | 52 | 15 | 67 |
| 2020 February | 36 | 15 | 51 |
| 2020 January | 26 | 19 | 45 |
| 2019 December | 41 | 21 | 62 |
| 2019 November | 20 | 6 | 26 |
| 2019 October | 19 | 25 | 44 |
| 2019 September | 14 | 5 | 19 |
| 2019 August | 31 | 17 | 48 |
| 2019 July | 21 | 38 | 59 |
| 2019 June | 17 | 23 | 40 |
| 2019 May | 36 | 33 | 69 |
| 2019 April | 51 | 28 | 79 |
| 2019 March | 28 | 12 | 40 |
| 2019 February | 24 | 26 | 50 |
| 2019 January | 22 | 8 | 30 |
| 2018 December | 27 | 29 | 56 |
| 2018 November | 54 | 24 | 78 |
| 2018 October | 71 | 22 | 93 |
| 2018 September | 43 | 23 | 66 |
| 2018 August | 1 | 0 | 1 |
| 2018 July | 2 | 0 | 2 |
| 2018 June | 2 | 0 | 2 |
| 2018 May | 7 | 0 | 7 |
| 2018 April | 19 | 0 | 19 |
| 2018 March | 25 | 0 | 25 |
| 2018 February | 12 | 0 | 12 |
| 2018 January | 14 | 0 | 14 |
| 2017 December | 16 | 0 | 16 |
| 2017 November | 9 | 0 | 9 |
| 2017 October | 13 | 0 | 13 |
| 2017 September | 10 | 0 | 10 |
| 2017 August | 9 | 0 | 9 |
| 2017 July | 5 | 2 | 7 |
| 2017 June | 18 | 7 | 25 |
| 2017 May | 20 | 7 | 27 |
| 2017 April | 9 | 10 | 19 |
| 2017 March | 6 | 3 | 9 |
| 2017 February | 12 | 3 | 15 |
| 2017 January | 10 | 3 | 13 |
| 2016 December | 28 | 10 | 38 |
| 2016 November | 36 | 5 | 41 |
| 2016 October | 26 | 13 | 39 |
| 2016 September | 34 | 3 | 37 |
| 2016 August | 35 | 3 | 38 |
| 2016 July | 17 | 5 | 22 |
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