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Hypothyroidism is Strongly Correlated with Mean Platelet Volume and Red Cell Distribution Width

: Objective: Hypothyroidism is characterized with insufficient production and release of thyroid hormones, and cause a variety symptoms including cold intolerance, constipation, deceleration in movement, and hair loss. It is associated with increased inflammatory burden. Therefore, we aimed to observe red cell distribution width (RDW) and mean platelet volume (MPV) levels, novel predictors of inflammation, in patients with hypothyroidism and to compare to those in healthy subjects. Materials and Methods: The subjects with hypothyroidism that show up in internal medicine outpatient clinics of Abant Izzet Baysal University Hospital between January 2020 and January 2021 were enrolled to the retrospective study. Healthy volunteers were enrolled as control subjects. MPV and RDW of the study groups were compared. Results: The median RDW level of hypothyroid and control groups were 13.3 (10-20.7) % and 15.3 (11.8-21.3) %, respectively (p<0.001). The median MPV level of hypothyroid and control groups were 10.2 (6.4-12.4) fL and 8.1 (5.4-11.5) fL, respectively (p<0.001). MPV levels greater than 9.47 fL have 80% sensitivity and 72% specificity in predicting hypothyroidism (AUC: 0.66 [95% CI: 0.58-0.74]; p<0.001). RDW levels greater than 13.4% have 80% sensitivity and 50% specificity in predicting hypothyroidism (AUC: 0.67 [0.82 [95% CI: 0.59-0.75]; p<0.001). Conclusion: We suggest that elevated MPV and reduced RDW levels should alert physicians for hypothyroidism in otherwise healthy subjects.

SPSS software (SPSS for Windows 15.0, IBM Co, Chicago, IL, USA) was used in conduction of the statistical analyses. Normality of the study variables was analyzed by Shapiro Wilk test. Independent samples t-test was used in comparison of the normally distributed variables and these variables were expressed as mean ± standard deviation. Mann Whitney U test was used comparison of the non-normally distributed variables and these variables were expressed as median (min-max). Categorical variables were expressed as numbers and percentage and compared with X 2 test. ROC curve analysis was also performed to determine the predictive ability of MPV and RDW in detecting hypothyroidism. It was considered statistically significant when the p value was lower than or equal to 5%.

RESULTS
We analyzed data of 188 subjects in the study; 94 were in group A (hypothyroidism) and 94 in group B (healthy control). Median age of group A and group B were 50  years and 55(26-79) years, respectively (p=0.53). The group A consisted of 12 (12.8%) men and 82 (87.2%) women while group B consisted of 56 (59.6%) men and 38 (40.4%) women (p<0.001).

DISCUSSION
In present study, we showed that hypothyroid subjects have greater MPV levels compared to healthy control group. MPV has significant positive correlation with the presence of hypothyroidism. Moreover, MPV has considerable sensitivity and specificity in detecting hypothyroidism. Another important outcome of the study was reduced RDW levels in hypothyroid subjects compared to healthy control group. In addition, RDW was inversely and significantly correlated with the presence of hypothyroidism in present retrospective cohort study.
Mean platelet volume is associated with infectious, metabolic and inflammatory conditions. There are also various studies in the literature regarding the relationship between MPV and thyroid diseases. Kutluturk et al. reported that MPV level were greater in subclinic hyperthyroid subjects than euthyroid subjects [23]. Kim et al. showed that MPV level were greater in subclinic hypothyroid patients [24]. Another study showed that patients with subclinical hypothyroidism had significantly higher MPV levels than those with euthyroid [25]. Sit et al. reported that higher MPV levels in malignant thyroid nodules compared to benign nodules [15]. In our study, we found that MPV levels were significantly higher in patients with hypothyroidism compared to the healthy control group. Moreover, we showed that MPV was inversely and significantly correlated with hypothyroidism.
We shall speculate about the possible mechanisms of MPV elevation in hypothyroidism. Hypothyroidism is considered as a condition characterized with clinic/subclinic inflammation [26]. Inflammatory markers increase in blood during inflammatory process and could interfere with platelet production in bone marrow, resulting in production of larger platelet. This situation become overt with increased MPV in laboratory studies.
RDW levels, another important point in our study, were found to be significantly lower in the hypothyroid group. Similarly, when the literature was examined, lower RDW values were found in patients with hypothyroidism [26]. It has been reported increased RDW values in patients with Hashimoto's thyroiditis [22]. It has been also reported that higher RDW values in malignant thyroid nodules compared to benign nodules [21]. Min Yu et al. reported that RDW levels were correlated with subclinical hypothyroidism subjects than euthyroid subjects [27]. In the literature, different studies have been stated about whether RDW is high or low in thyroid disorders.

LIMITATIONS
Our study has two limitations: first limitation could be relatively small study population and second limitation could be retrospective design. These limitations make our results difficult to interpret in clinical practice. However, present study is important by showing increased MPV and decreased RDW in subjects with hypothyroidism, which may add a lot to the current literature knowledge.

CONCLUSION
We suggest that elevated MPV and reduced RDW levels should alert physicians for hypothyroidism in otherwise healthy subjects. Yet, prospective studies with greater study population are required to confirm our results.