TSH and TPOAB as Predictors of Thyroid Disease in
                        Diabetic Patients...
Bedone et al                                                                                    The Endocrinologist • Volu...
The Endocrinologist • Volume 18, Number 2, April 2008                                                                     ...
Bedone et al                                                                            The Endocrinologist • Volume 18, N...
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TSH and TPOAB as Predictors of Thyroid Disease in Diabetic ...

  1. 1. PRELIMINARY STUDY TSH and TPOAB as Predictors of Thyroid Disease in Diabetic Patients Raquel V. Bedone, MD,* Walkyria P. Pimenta, MD, PhD,* Lıdia R. Carvalho, PhD,† ´ and Glaucia M.F.S. Mazeto, MD, PhD* ´ diabetic patients followed up in our Diabetes Clinic between Abstract: We tested the values of antithyroid peroxidase antibody and thyrotropin levels for the development of thyroid dysfunction in 2000 and 2005. 109 diabetic patients. Baseline thyrotropin level was a predictor of Demographic data, DM type and year of diagnosis, thyroid dysfunction in diabetic patients, excluding nodular disease. details of previous thyroid diagnoses, and results of thyroid The antithyroid peroxidase antibody had no predictive value for autoantibody and hormone measurements, as well as thyroid thyroid dysfunction. ultrasound (US) were taken from records of first visit to the clinic. Thyroid function testing and US were also performed Key Words: TSH, TPOAB, thyroid dysfunction, diabetes for each subsequent year of follow-up. Thyroid disorder was mellitus, predictors defined as thyroid dysfunction or thyroid nodular disease. (The Endocrinologist 2008;18: 81– 84) Thyroid function was classified as normal, if both TSH and free T4 were within their reference ranges; hypothyroid if TSH was elevated and hyperthyroid if TSH was suppressed. Hypothyroidism and hyperthyroidism were further classified as overt if free T4 was outside the reference range, and D iabetes mellitus (DM) is a chronic disease with an increasing incidence.1 Some studies show that the prev- alence of thyroid dysfunction,2,3 and thyroid disease4 is subclinical if free T4 was normal. Nodular disease was confirmed by the presence of higher in patients with DM than in the general population.5 nodules on US. The development of nodules was considered Thus, screening for thyroid disorders in individuals with to have occurred when the baseline US was normal and diabetes might be recommended. However, there is no con- thyroid nodules were found during follow-up. sensus as to best markers for this screening. Auto antibodies were considered positive when Thyroid autoantibodies are more frequent in patients TPOAB levels exceeded the reference values. with DM than in the general population. Higher prevalence Free T4 and TSH were measured by chemiluminis- rates have been reported in type 1 DM6 than in type 2 DM.7 cence with normal values ranging from 0.8 to 1.9 ng/dL and In the first Whickham survey, the presence of autoantibodies 0.4 to 4.0 UI/mL, respectively (DPC, Los Angeles, CA). was associated with a 13-fold increase in the likelihood of TPOAB was determined by chemiluminiscence with values developing thyroid dysfunction over 20 years.5 Warren et al considered normal when 35 UI/L (DPC). showed that a high-normal thyroid-stimulating hormone Nodular disease was assessed by thyroid US (Toshiba, (TSH) could predict later thyroid dysfunction.8 10 MHz transducer). The aim of this study was to compare the predictive value of antithyroid peroxidase antibody (TPOAB) and TSH Data Analysis levels for later thyroid disease in patients with DM. Categorical variables were compared by the 2 test. Means were compared with Student t test. Receiver-operating PATIENTS AND METHODS characteristics (ROC) curves were used to determine TSH and thyroid outcome “threshold values.” Data Collected Thyroid outcomes were analyzed by the method of This study was approved by the Committee of Research Kaplan-Meier using the log-rank test and Cox regression.9 Ethics of Botucatu Medical School. This retrospective anal- TSH levels between groups were compared using Student t ysis was based on the case notes and medical records of 180 test for quantitative variables and test of the difference between proportions for the remaining variables Significance level was set at 5.0%. From the *Departments of Medicine and †Bioestatistic, Botucatu Medical School, Sao Paulo State University, Unesp, Brazil. ˜ Reprints: Glaucia M.F.S. Mazeto, MD, PhD, Departamento de Clınica ´ ´ Medica, FMB, Unesp 18618-000, Botucatu, SP, Brazil. E-mail: gmazeto@ ´ RESULTS Copyright © 2008 by Lippincott Williams & Wilkins Thyroid Autoantibodies ISSN: 1051-2144/08/1802-0081 Among the 109 patients studied, positive TPOAB lev- DOI: 10.1097/TEN.0b013e318169e3b2 els were found in 4 individuals. Two had type 1 DM and 2 The Endocrinologist • Volume 18, Number 2, April 2008 81
  2. 2. Bedone et al The Endocrinologist • Volume 18, Number 2, April 2008 TABLE 1. Characteristics of the 109 Patients Studied line TSH in these patients was 2.44 1.23 UI/mL. Two patients, whose mean baseline TSH was 0.65 0.08 UI/ Patients With Patients With mL, developed subclinical hyperthyroidism. Total of Patients Type 1 DM Type 2 DM Parameter (n 109) (n 25) (n 84) No. males (%) 41 (37.6) 10 (40) 31 (36.9) Nodular Development During Follow-Up Mean (SD) age (yr) 55.5 (16.4) 33.6 (8.32) 62.37 (11.26) A total of 21 patients developed nodules during the at baseline follow-up period: 19 of these had type 2 DM. The mean Number (%) with 4 (3.6) 2 (8) 2 (2.4) baseline TSH was 1.96 0.73 UI/mL. positive TPOAB Mean (SD) baseline 1.8 (0.88) 1.94 (0.85) 1.78 (0.91) TSH ( UI/mL) Predictors of Thyroid Dysfunction and Nodular DM mean (SD) 15.2 (7.0) 14.84 (7.27) 15.45 (7.01) Development duration (yr) Figure 1 shows the ROC curve for baseline TSH as a DM indicates diabetes mellitus; SD, standard deviation; TPOAB, antithyroid predictor of thyroid dysfunction. The intersection with a peroxidase antibody; TSH, thyrotropin. diagonal was assumed to provide optimum specificity and sensitivity, and corresponded to a baseline TSH concentration had type 2 DM. All were women. Mean baseline TSH value of 2.48 UI/mL. This was taken as a threshold to classify was 2.09 1.29 UI/mL in these patients and 1.8 0.88 patients into 2 categories: baseline TSH 2.48 UI/mL, and UI/mL in those with negative autoantibodies (P 0.54) baseline TSH 2.48 UI/mL. (Table 1). Six of 25 patients (24.0%) with baseline TSH 2.48 UI/mL developed thyroid dysfunction, whereas only 5 of 84 Thyroid Dysfunction During Follow-Up patients (6.0%) with baseline TSH 2.48 UI/mL did it All 109 patients were followed for a mean period of 35 (P 0.009). Curves for survival free of thyroid dysfunction, months (range, 2–100 months). During follow-up, 11 patients constructed for possible predictors, also differed statistically develop thyroid dysfunction: 2 had type 1 DM and 9 had type in both groups (Fig. 2). Mean time to develop dysfunction 2 DM. Nine patients developed hypothyroidism. Mean base- was 30 14 months in the group with baseline TSH 2.48 1 0,9 0,8 0,7 0,6 sensitivity 0,5 0,4 0,3 0,2 0,1 0 0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 1-specificity FIGURE 1. Receiver-operating characteristics curve for TSH as a predictor of thyroid dysfunction (threshold: TSH 2.48 UI/mL). 82 © 2008 Lippincott Williams & Wilkins
  3. 3. The Endocrinologist • Volume 18, Number 2, April 2008 TSH and TPOAB FIGURE 2. Kaplan-Meier curves for survival free of thyroid dysfunction in diabetic patients ac- cording to TSH levels (log-rank, P 0.018). TABLE 2. Outcomes in 109 Patients Categorized by TABLE 3. Characteristics of 109 Diabetic Patients, Baseline TSH Concentration and TPOAB Status Categorized by Baseline TSH Level Negative TPOAB Positive TPOAB Baseline TSH Baseline TSH Baseline TSH (n 105) (n 4) <2.48 >2.48 UI/mL UI/mL 2.48 UI/mL 77 Euthyroid 2 Euthyroid Parameter (n 84) (n 25) P 4 Thyroid dysfunction 1 Thyroid dysfunction 2 Subclinical 1 Subclinical No. males (%) 35 (41.6) 6 (24) 0.11 hyperthyroid hyperthyroid Mean (SD) age (yr) at 56.1 (17.2) 53.7 (13.7) 0.53 1 Hypothyroid baseline 1 Subclinical Number (%) with positive 3 (3.6) 1 (4) 0.54 hypothyroid TPOAB 2.48 UI/mL 19 Euthyroid 1 Thyroid dysfunction: Mean (SD) baseline TSH 1.44 (0.57) 3.1 (0.52) 0.00 ( UI/mL) 5 Thyroid dysfunction: 1 Hypothyroid DM mean (SD) duration 15.4 (7.2) 14.7 (6.6) 0.65 3 Subclinical (yr) hypothyroid No. patients with type 1 19 (22.6) 6 (24) 0.56 2 Hypothyroid DM (%) TSH indicates thyrotropin; TPOAB, antithyroid peroxidase antibody. No. patients with type 2 65 (77.4) 19 (76) 0.44 DM (%) TSH indicates thyrotropin; SD, standard deviation; TPOAB, antithyroid peroxidase antibody; DM, diabetes mellitus. UI/mL and 25 14 months in the group with baseline TSH 2.48 UI/mL. Table 2 shows thyroid function characteris- tics according to baseline TSH concentration. previous study,4 in which a frequency of 52% was observed No differences in gender, mean age, positive TPOAB in the same geographical area. percent, mean DM duration, type 1 and type 2 DM rates were We found that 10.1% of diabetic patients with normal found between groups (Table 3). baseline thyroid status developed thyroid dysfunction during TPOAB status and TSH concentration were entered as a mean follow-up of 35 months. In studies performed at covariates in a Cox regression model, to determine whether primary care centers in England, the prevalence of thyroid the presence of TPOAB and TSH 2.48 UI/mL were dysfunction was 11% in patients with DM.3 In the United predictive regardless of thyroid dysfunction. TPOAB status Kingdom, 6% of euthyroid diabetic patients developed ab- was not significant in this model (risk ratio 3.24; 95% normal thyroid function over a mean follow-up period of 6 confidence interval 0.67–15.76), whereas TSH was signifi- years.8 Our data show that the development of thyroid dys- cant (risk ratio 4.93, 95% confidence interval 1.38 –17.58). function is more frequent in patients with higher normal Therefore, baseline TSH 2.48 UI/mL remained indepen- baseline TSH levels. Vanderpump et al5 and Warren et al,8 dently predictive of thyroid dysfunction (Table 2). demonstrated that the risk of developing thyroid dysfunction Neither TSH nor TPOAB concentrations were predic- was increased when baseline TSH 2.0 mU/L, and 1.53 tive of nodular development. mU/L, respectively. Our group of patients with baseline TSH 2.48 UI/mL and TSH 2.48 UI/mL developed thyroid dys- DISCUSSION function over a mean period of 25.00 14.35 and 30 14 The prevalence of thyroid disorder in diabetic patients months, respectively. This finding suggests that annual TSH in our study was 57%. This is similar to the rate found in a measurement is advisable in diabetic patients. © 2008 Lippincott Williams & Wilkins 83
  4. 4. Bedone et al The Endocrinologist • Volume 18, Number 2, April 2008 CONCLUSIONS 5. Vanderpump MPJ, Tunbridge WMG, French JM, et al. The incidence of thyroid disorders in the community. A twenty-year follow-up of the In our study, an increased TSH predicted thyroid dysfunc- Whickham survey. Clin Endocrinol. 1995;43:55– 68. ´ tion but not nodular disease. Elevated TPOAB was not predic- 6. Souza OLR, Diehl LA, Carleto LD Jr, et al. Prevalencia de auto- ˆ tive for either thyroid dysfunction or nodule development. imunidade tireoideana em um grupo de pacientes com diabetes mel- litus Tipo 1 em Londrina, PR. Ar Qbras Endocrinol Metab. 2005;49: REFERENCES 228 –233. 1. Sherwin RS. Diabete melito. In: Goldman L, Ausiello D, eds. Cecil-Tratado de 7. Landin-Olsson M, Karlsson FA, Lenmark A, et al. Islet cell and thyro- Medicina Interna. Rio deJaneiro, RJ: Guanabara Koogan; 2005:1658–1692. gastric antibodies in 633 consecutive 15- to 34-year old patients in 2. Perros P, McCrimmon RJ, Shaw G, et al. Frequency of thyroid dysfunction in diabetes incidence study in Sweden. Diabetes. 1992;41:1022–1027. diabetic patients: value of annual screening. Diabet Med. 1995;12:622–627. 8. Warren RE, Perros P, Nyirenda MJ, et al. Serum thyrotropin is a better 3. Smithson MJ. Screening for thyroid dysfunction in a community popu- predictor of future thyroid dysfunction than thyroid autoantibody status in lation of diabetic patients. Diabet Med. 1998;15:148 –150. biochemically euthyroid patients with diabetes: implications for screen- 4. Pimenta WP, Mazeto GMFS, Callegaro CF, et al. Associacao de Tire-¸˜ ing. Thyroid. 2004;14:853– 857. opatias em Uma Populacao de Pacientes com Diabetes. Ar Qbras Endo- ¸˜ 9. Matthews DE, Farewell VT. Using and Understanding Medical Statistics. crinol Metab. 2005;49:234 –240. Karger Basel; 1996. 84 © 2008 Lippincott Williams & Wilkins