LA PRESION INTRAOCULAR DISMINUYE DURANTE EL TRATAMIENTO SUSTITUTIVO CON LEVOTIROxiNA EN EL HIPOTIROIDISMO CLINICO
Intraocular pressure decreases during levothyroxine replacement therapy for overt hypothyroidism
F. Almodóvar, F. Muñoz, HF. Escobar-Morreale, G. Rebolleda, C. Varela
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In 1965, McLenachan and Davies<span class="elsevierStyleSup">1</span> prospectively compared 100 patients diagnosed with POAG and 100 patients diagnosed with closed-angle glaucoma, and, based on the results of a <span class="elsevierStyleSup">131</span>I thyroid uptake, found thyroid hypofunction in 45% of POAG patients, as compared to 13% of the patients with closed-angle glaucoma. </p><p class="elsevierStylePara"> The association between hypothyroidism and POAG have been also supported by later studies, in which a 23.4% prevalence of hypothyroidism, as diagnosed by an increased plasma TSH concentration, was found in patients with POAG<span class="elsevierStyleSup">2</span>. Therefore, hypothyroidism has been considered as a risk factor for POAG<span class="elsevierStyleSup">3,4</span>. The pathophysiologic link between hypothyroidism and POAG is also supported by the recent finding of an increased intraocular pressure (IOP), in patients with subclinical hypothyroidism, which was decreased and even normalized after thyroid replacement therapy<span class="elsevierStyleSup">5</span>. However, in the latter study none of the patients matched criteria for clinically significant POAG<span class="elsevierStyleSup">5</span>, a result that might have been influenced by the lack of overt hypothyroidism in these subjects. </p><p class="elsevierStylePara"> Finaly, autoimmune diseases have been suggested to increase the risk for POAG<span class="elsevierStyleSup">6</span>, and POAG could not be related to thyroid function abnormalities, but to its autoimmune <br></br> origin. </p><p class="elsevierStylePara"> In the present survey we have studied the IOP and the prevalence of POAG in a group of patients with overt hypothyroidism, focusing on the role of autoimmunity, and on the influence of levothyroxine replacement therapy, on the changes in IOP. </p><p class="elsevierStylePara"><span class="elsevierStyleBold">SUBJECTS AND METHODS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Subjets</span></p><p class="elsevierStylePara"> Eighteen patients with overt hypothyroidism, 3 men and 15 women, age (mean ± SEM) 52 ± 6 years, range 20-80, were selected for the study. Patients were divided in two groups according to the etiology of the hypothyroidism. Group 1 included 7 patients with previous thyroid ablation because of differentiated thyroid carcinoma. These patients were studied 1 month after thyroid hormone withdrawal, which was routinely scheduled for a whole body <span class="elsevierStyleSup">131</span>I scan. Group 2 included 11 consecutive patients with overt primary autoimmune hypothyroidism. In this group, the time of duration of hypothiroidism prior to diagnosis was estimated from their clinical records. </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Methods</span></p><p class="elsevierStylePara"> At baseline, serum free T4 (FT4) and TSH concentrations, and microsomal (MSA) and thyroglobulin (TGA) antibodies were measured in all the patients. </p><p class="elsevierStylePara"> All patients underwent a complete ocular examination. Intraocular pressure was measured with a Goldmann tonometer. Each eye was explored separately, the right eye being examined first, the procedure was repeated 3 times and the mean values of IOP (MIOP) measurement for each eye was calculated. Visual fields and ophthalmoscopic exams were also performed in every patient to disclose visual field defects or optic nerve damage. Primary open-angle glaucoma was defined by a IOP > 21 mmHg in any eye, together with decreased visual sensitivity or optic nerve defects. Patients showing closed-angle glaucoma, pseudoexfoliation, pigment dispersion or secondary open-angle glaucoma were excluded from the study. </p><p class="elsevierStylePara"> Thyroid function tests and ocular examination were repeated after 3 months of levothyroxine replacement therapy. The MIOP determination, and the visual field and ophthalmoscopic exams were performed by the same observer at baseline and month 3. </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Assays</span></p><p class="elsevierStylePara"> Serum FT4 concentration was measured by radioimmunoassay (Biocode biotechnology, Sclessin, Belgium) with a normal range of 0.8-2.2 ng/dl. Serum TSH levels were performed by immunoradiometric assay (Count, Llambeis, United Kingdom) with a normal range of 0.31-5.56 µ U/ml. The serum titers of MSA and TGA were determined by agglutination assay (Serodia, Fujirato-In, Tokyo, Japan) with a normal range of 1 (logaritmic transformation). </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical Analysis</span></p><p class="elsevierStylePara"> The results are expressed as mean ± SEM in the text and table 1. The comparison between Groups were made by unpaired t test, and the evolution of MIOP before and during levothyroxine replacement therapy was evaluated by paired t test. The relationships between IOPM and other clinical or biochemical variables (visual acuity) were analyzed by Pearson's correlation analysis. The titers of microsomal and thyroglobulin autoantibodies underwent to logarithmic transformation before correlation analysis. </p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara"> Primary open-angle glaucoma was not present in any patient, either during overt hypothyroidism, or after replacement therapy with oral levothyroxine. As expected, serum FT4 levels were low, and serum TSH concentrations were elevated, at baseline (table 1). In Group 1 the dose of levothyroxine was titrated to obtain normal serum FT4 levels together with suppressed TSH values, in order to avoid stimulation of tumor growth by the latter (table 1). In Group 2, in which the estimated duration of hypothyroidism was 14 ± 4 months, the dose of levothyroxine was adjusted to maintain normal serum FT4 and TSH concentrations (table 1). As expected, serum FT4 was higher, and serum TSH was lower, in Group 1 as compared to Group 2 (table 1). </p><p class="elsevierStylePara"><img src="1621.GIF" width="476" height="114"></img></p><p class="elsevierStylePara"> At baseline, the MIOP was similar in both groups. When considering the 18 studied patients together, the MIOP decreased after replacement therapy (fig. 1). Despite the differences in the FT4 and TSH values reached after 3 months of replacement therapy among the groups of patients, the MIOP decreased to a similar extent in both groups (table 1). When studying patients individually, 2 patients presented increased IOP values (> 21 mmHg) in both eyes, and 2 patients presented increased IOP in 1 eye, at diagnosis. These increased IOP values decreased below 21 mmHg during replacement therapy in all these patients. </p><p class="elsevierStylePara"><img src="163F1.GIF" width="229" height="281"></img></p><p class="elsevierStylePara"> Finally, the MIOP showed no significant correlation with the logarithmic of the titers of microsomal (r = 0.26, nonsignificant) or thyroglobulin (r = 0.31, nonsignificant) antibodies in Group 2. No correlation was detected between the MIOP and the estimated duration of hypothyroidism (r = 0.25, nonsignificant). </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> Our results demonstrate that MIOP decreases after treatment of overt hypothyroidism with levothyroxine replacement therapy. These data are in agreement with the findings of a reversible increase in IOP in patients with subclinical hypothyroidism<span class="elsevierStyleSup">5</span>. However, none of the patients in our series presented POAG during overt hypothyroidism, as occurred in the patients with subclinical hypothyroidism described by Centanni et al<span class="elsevierStyleSup">5</span>. </p><p class="elsevierStylePara"> The association between hypothyroidism and POAG is, at least, controversial<span class="elsevierStyleSup">7</span>. An increased prevalence of thyroid dysfunction has been reported in patients with POAG<span class="elsevierStyleSup">1,2</span>, and therefore hypothyroidism has been considered as a risk factor for POAG<span class="elsevierStyleSup">3,4</span>. However, the methods for evaluating thyroid dysfunction in the study of McLenachan and Davies<span class="elsevierStyleSup">1</span> had low sensitivity and specificity, and the prevalence of newly diagnosed hypothyroidism in the study of Smith et al<span class="elsevierStyleSup">2</span> was not different in patients with POAG as compared to the control group. Thus, the increased prevalence of hypothyroidism in patients with POAG found in this study was related to a significant number of patients previously diagnosed of hypothyroidism, who were under replacement therapy<span class="elsevierStyleSup">2</span>, casting doubt upon the pathophysiologic link between thyroid hypofunction and the development of glaucoma in their series. In a recent study, Gillow et al have found a prevalence of hypothyroidism similar to that of the general population in a large series of POAG patients attending a specialist glaucoma clinic<span class="elsevierStyleSup">7</span>. Moreover, the high prevalence of POAG in patients with hypothyroidism reported by Smith et al in a previous study<span class="elsevierStyleSup">8</span> was mainly based on tonography and tonometry measurements, lacking loss of visual acuity or optic nerve damage as a requirement for the definition of POAG. </p><p class="elsevierStylePara"> Taken together with the results of Centanni et al<span class="elsevierStyleSup">5</span> in subclinical hypothyroidism, our present results in patients with overt primary hypothyroidism suggest that, in oposition to what was previously believed<span class="elsevierStyleSup">3,4</span>, clinically significant POAG is a rare complication of thyroid hypofunction, not warranting IOP measurement in otherwise asymptomatic hypothyroid patients. Moreover, as patients with increased IOP in our study, and in the study of Centanni et al<span class="elsevierStyleSup">5</span>, did not present full POAG criteria, the increase in IOP in hypothyroid patients, and the decrease in IOP during levothyroxine replacement therapy, suggests that thyroid hormones are involved in the physiologic control of IOP. The finding of similar MIOP after short and long standing hypothyroidism, along with a lack of correlation between the estimated duration of thyroid hypofunction and the MIOP in group 2, also suggests that changes in the latter are related to a decrease in thyroid hormone levels. </p><p class="elsevierStylePara"> Finally, our data do not support the previous hypothesis of an autoimmune origin of POAG<span class="elsevierStyleSup">6</span>, as no difference in MIOP was found among the groups of patients with autoimmune and non-autoimmune hypothyroidism. </p><p class="elsevierStylePara"> In conclusion, replacement therapy with levothyroxine for overt primary hypothyroidism results in a decrease in MIOP. However, only 4 patients had mildly increased IOP when hypothyroid, and none of them presented POAG. Therefore, our data do not support a primary role of thyroid hypofunction in the development of POAG, although it is possible that, in patients with previous abnormalities in the regulation of IOP, hypothyroidism might contribute to the development of POAG. </p>" "tienePdf" => false "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec204448" "palabras" => array:4 [ 0 => "Presión intraocular" 1 => "Hipotiroidismo" 2 => "Hormona tiroidea" 3 => "Levotiroxina" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec204449" "palabras" => array:4 [ 0 => "Intraocular pressure" 1 => "Hypothyroidism" 2 => "Thyroid hormone" 3 => "Levothyroxine" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span class="elsevierStyleBold">Objetivo:</span> Analizar la influencia del hipotiroidismo primario clínico sobre la presión intraocular (PIO). <br/> <span class="elsevierStyleBold">Plan:</span> Siete pacientes con hipotiroidismo primario no autoinmune (grupo I) y 11 pacientes con hipotiroidismo primario autoinmune (grupo 2) fueron evaluados antes y 3 meses después del tratamiento sustitutivo con levotiroxina. <br/> <span class="elsevierStyleBold">Sujetos y Métodos:</span> Todos los pacientes fueron sometidos a una exploración visual completa incluyendo campos visuales y medidas seriadas de PIO con un tonómetro de Goldmann, Se midieron T4 libre y tirotropina séricas, y se determinaron los títulos de anticuerpos microsomales y de tiroglobulina, basales y después de corregir el hipotiroidismo con levotiroxina. <span class="elsevierStyleBold">Resultados:</span> La PIO media (PIOM) disminuyó después de 3 meses de tratamiento sustitutivo con respeto a la situación basal de ambos grupos de pacientes hipotiroides (media ± EEM, grupo I: basal 19,0 ± 0,6 mmHg, después del tratamiento 17,1 ± 0,6 mmHg; p < 0,05; grupo 2: basal 17,8 ± 0,7, después del tratamiento 15,5 ± 0,8; p < 0,05). No hubo diferencias en la PIOM entre los grupos de pacientes. Dos pacientes presentaron PIO > 21 mmHg en ambos ojos, y 2 pacientes tuvieron PIO > 21 mmHg durante la administración de levotiroxina. Ninguno de los pacientes presentó disminución de la agudeza visual ni daño en el nervio óptico, y así, ningún paciente fue diagnosticado con glaucoma primario de ángulo abierto clínicamente significativo (GPAA). La PIOM no demostró ninguna correlación con la duración estimada del hipotiroidismo autoinmune, ni con los títulos de autoanticuerpos tiroideos. <br/> <span class="elsevierStyleBold">Conclusiones:</span> La presión intraocular disminuye durante el tratamiento con levotiroxina en pacientes con hipotiroidismo clínico, independientemente de la etiología y de la duración de la hipofunción tiroidea. A pesar del incremento en la PIO en algunos de estos pacientes, no se halló con frecuencia, un GPAA clínico, lo que sugiere que las hormonas tiroideas pueden estar implicadas en la regulación normal de la PIO" ] "en" => array:1 [ "resumen" => "<span class="elsevierStyleBold">Objective:</span> To analyze the influence of overt primary hypothyroidism on intraocular pressure (IOP). <br/> <span class="elsevierStyleBold">Design:</span> Seven patients with non-autoimmune primary hypothyroidism (Group 1) and 11 patients with autoimmune primary hypothyroidism (Group 2) were evaluated before and 3 months after replacement therapy with levothyroxine. <br/> <span class="elsevierStyleBold">Subjects and methods:</span> All patients underwent a complete ocular examination including visual fields and serial measurements of IOP with a Goldmann tonometer. Measurement of serum free T4 and thyrotropin concentrations, as well as determinations of the serum titers of microsomal and thyroglobulin autoantibodies, were performed at baseline and after correction of hypothyroidism with levothyroxine therapy. <br/> <span class="elsevierStyleBold">Results:</span> The mean IOP (MIOP) decreased after 3 months of replacement therapy with respect to baseline in both groups of hypothyroid patients (mean ± SEM, Group 1: baseline 19.0 ± 0.6 mmHg, after treatment 17.1 ± 0.6 mm Hg, p < 0.05; Group 2: baseline 17.8 ± 0.7, after treatment 15.5 ± 0.8, p < 0.05). There were no differences in the MIOP among the groups of patients. Two patients showed IOP > 21 mmHg in both eyes, and 2 patients had IOP > 21 mmHg in one eye. In all the patients, IOP decreased below 21 mmHg during levothyroxine administration. None of the patients presented decreased visual acuity or optic nerve damage, and thus no patient was diagnosed with clinically significant primary open-angle glaucoma (POAG). The MIOP showed no correlation with the estimated duration of autoimmune hypothyroidism, or with the titers of thyroid autoantibodies. <br/> <span class="elsevierStyleBold">Conclusions:</span> Intraocular pressure decreases during replacement therapy with levothyroxine in patients with overt hypothyroidism, independently of the etiology and the duration of thyroid hypofunction. Despite the increase in IOP in some of these patients, clinical POAG is not a frequent finding, suggesting that thyroid hormones might be involved in the normal regulation of IOP." ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Glaucoma and the thyroid." 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"idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Centanni M" 1 => "Cesareo R" 2 => "Verallo O" 3 => "Brinelli M" 4 => "Cannettieri G" 5 => "Viceconti N et al." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "1997" "volumen" => "136" "paginaInicial" => "595" "paginaFinal" => "598" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9225722" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Immune-related disease and normal-tension glaucoma. A case-control study." 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Article information
ISSN: 15750922Original language: English
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