Hypothyroidism is a clinical disorder, characterized by inadequate production or action of thyroid hormones. It is the most common endocrine disorder affecting individuals globally. It presents itself in the form of either overt hypothyroidism characterized by high levels of thyroid-stimulating hormone (TSH) and low free thyroxine (FT4) or subclinical hypothyroidism whereby TSH is high with FT4 being on the normal level. Clinical manifestations can consist of fatigue, weight gain, intolerance to colds, constipation, and anemia among others, and it can resemble other systemic diseases which makes this condition difficult to diagnose [1, 2]. There is a close relationship between iron metabolism and thyroid functions. Erythropoiesis and iron metabolism require thyroid hormones, and thyroid peroxidase (TPO), which takes part in thyroid hormone synthesis, is an important cofactor of iron [3]. The presence of iron deficiency can worsen the thyroid and the presence of hypothyroidism can interfere with the iron pathways, resulting in reduced gastrointestinal absorption of iron and distorted iron storage. One of the established symptoms in hypothyroid patients is anemia which is often accompanied by normocytic normochromic or microcytic hypochromic forms [4]. Serum ferritin is an acute phase reactant and intracellular iron storage protein that shows the body's iron stores. It plays an important key to the early detection of iron deficiency which may be identified prior to the occurrence of overt anemia. Low ferritin concentration in hypothyroid patients may be explained by long-standing blood loss in women with menorrhagia or reduced absorption due to intestinal hypomotility [5]. On the other hand, increased ferritin can be seen in hypothyroidism, which could be suggestive of inflammation or metabolic disturbances such as in cases of autoimmune thyroiditis [6]. Several studies have shown that there is a strong correlation between levels of serum ferritin and the thyroid condition. Because serum ferritin may be disproportionately affected compared with hemoglobin or other hematologic indices in hypothyroid patients. This makes ferritin a potentially useful marker in these conditions as a measure both of diagnosis and progress of the disease [7]. In hypothyroid persons, the measurement of ferritin may be used to identify comorbid iron deficiency, guide iron supplementation, and improve response to thyroid hormone replacement therapy. Moreover, treating the underlying iron deficiency has been shown to improve thyroid functions in patients, particularly in cases of subclinical hypothyroidism [8]. Since there are overlapping symptoms and physiological interdependence of iron metabolism and thyroid functions, the evaluation of serum ferritin in patients with hypothyroidism is clinically significant. Early identification and correction of iron imbalance can improve treatment outcomes, reduce fatigue, and improve cognitive functions as well as metabolic recovery. The current study aimed to evaluate the serum ferritin levels in patients with hypothyroidism and assess its clinical relevance, particularly in relation to anemia, symptom severity, and treatment response.

This cross-sectional analytical study was done in the Department of General Medicine along with the Department of Biochemistry at a tertiary care teaching hospital. The duration of the study was 12 months. Institutional ethical approval was obtained for the study after explaining the nature of the study in vernacular language. Written consent was obtained from all the participants of the study before enrolment.

A total of 100 individuals aged 18 to 65 years were recruited and divided into two groups:

• Group A (Cases): 50 patients newly diagnosed with primary hypothyroidism, based on elevated serum TSH and low free T4 levels.
• Group B (Controls): 50 age- and sex-matched healthy euthyroid individuals with no known thyroid disorder or chronic illness.

Inclusion Criteria

1. Patients with confirmed primary hypothyroidism (TSH > 10 μIU/mL and/or low FT4).
2. Both males and females aged between 18–65 years.
3. Patients not on thyroid hormone or iron supplementation at the time of recruitment.
4. Willing to participate in the study voluntarily

Exclusion Criteria

1. Pregnant or lactating women.
2. Individuals with chronic inflammatory diseases, liver disorders, renal failure, or malignancy.
3. Patients with a history of recent blood transfusion or hemoglobinopathies.
4. Patients on corticosteroids, antiepileptics, or other medications are known to affect iron or thyroid metabolism.

After enrolment, a detailed history and clinical examination were recorded using a structured proforma from all the cases of the study. Venous blood samples were collected after overnight fasting. The following investigations were carried out which included Thyroid function tests: TSH and free T4 measured by chemiluminescence immunoassay. Serum ferritin: Measured using electrochemiluminescence immunoassay (ECLIA). Hemoglobin, and RBC indices: Analyzed using an automated hematology analyzer. Serum iron, total iron-binding capacity (TIBC), and peripheral smear were done where indicated to assess iron status comprehensively.

The primary outcome was the comparison of serum ferritin levels between hypothyroid and euthyroid individuals. Secondary outcomes included correlation of ferritin with hemoglobin levels, severity of hypothyroidism (based on TSH values), and clinical symptoms like fatigue and pallor.

Statistical Analysis: All the available data was refined, segregated, and uploaded to an MS Excel spreadsheet and analyzed by SPSS version 23 in Windows format. The continuous variables were represented as frequency, mean, standard deviation, and percentages. Categorical variables were analyzed by the Mann-Whitney U test for continuous variables and the Chi-square test for categorical data. Spearman’s correlation was used to assess associations. A p-value < 0.05 was considered statistically significant.

Table 1 depicts the baseline characteristics of each participant. A critical analysis of the table shows that the mean age of the cohort was similar (44.6 vs. 43.2 years) p = 0.51 and not significant. The gender distribution showed a female predominance in both groups, with no significant difference (p = 0.82). The mean BMI of the hypothyroid group A was higher as compared to the euthyroid patients group B however the values did not reach levels of significance (p=0.23). The thyroid function tests showed marked and significant differences between the two groups. The mean TSH levels were significantly elevated in hypothyroid patients compared to euthyroid patients (38.7 ± 16.9 μIU/mL vs. 2.4 ± 0.9 μIU/mL) and p= < 0.001. The free T4 levels were significantly lower in Group A which confirms the biochemical diagnosis of hypothyroidism in Group A.

      *Significant

The iron profile of the cases and controls is presented in Table 2. The analysis of the table shows that serum ferritin was significantly lower in Group A (32.6 ± 14.2 ng/mL) than in Group B (68.9 ± 22.5 ng/mL) the p-value was (<0.001). In addition, serum iron levels were significantly reduced in hypothyroid individuals (48.3 vs. 92.1 μg/dL) p < 0.001. These results show that iron deficiency was highly prevalent among hypothyroid patients and could be the cause of anemia and clinical symptoms.

     *Significant

Table 3 below is a comparison of the hematological indices and peripheral smear results of the two groups. There was a significant reduction in the mean hemoglobin (11.2 ± 1.4 g/dL) in hypothyroid patients than euthyroid controls (13.8 ± 1.1 g/dL; p < 0.001). Indices of red blood cells also significantly changed: reduced volume of mean corpuscle (MCV: 78.5 vs. 88.2 fL), hemoglobin of corpuscle (MCV: 25.8 vs. 29.7 pg), and red cell distribution width (RWD: 16.9% vs. 13.1%) was observed in the hypothyroid group (p < 0.001 for all). Moreover, 76 percent of the hypothyroid group showed microcytic hypochromic changes on peripheral smears as opposed to 6 percent of euthyroid subjects (p < 0.001), thereby demonstrating a high correlation between hypothyroidism and iron-deficiency anemia.

            *Significant

There is a strong correlation between a range of biochemical parameters in the hypothyroid group, as depicted in Table 4. The serum ferritin had a strong negative correlation with TSH (ρ = -0.72; p<0.01) and a positive correlation with hemoglobin (ρ = 0.68) and free T4 (ρ = 0.61) indicating that the lower ferritin, the more severe hypothyroidism and anemia. The hemoglobin also had a negative correlation with TSH (ρ = -0.65), and a positive one with free T4 (ρ = 0.59). The severity of the symptoms had moderate negative correlations with ferritin (ρ = -0.57) and hemoglobin (ρ = -0.52), which seemed to imply worsened clinical manifestations related to increased iron loss and anemia. All of the correlations proved to be significant.

                                              *Significant

Table 5 presents the comparison of clinical symptoms and laboratory parameters according to the ferritin level in hypothyroid patients. Within the group of ferritin <30 ng/mL (n=32) the prevalence of fatigue and pallor was considerably higher (96.9% and 87.5%, respectively) than in the group with ferritin >=30 ng/mL (66.7% and 44.4%; p < 0.05). There were more cases of hair loss in the group of low ferritin, without a statistically significant result (p = 0.09). Cold intolerance: There was no difference. Notably, mean hemoglobin levels were very low in the low ferritin group (10.2 + 1.1 g/dL vs. 12.9 + 1.0 g/dL; p < 0.001) and TSH was much higher (46.3 vs. 24.1 l/mL; p < 0.001) showing that ferritin cardinality is of clinical importance when considering hypothyroid patients.

      *Significant

This current study evaluated serum ferritin values and their clinical indications in patients with hypothyroidism. The results of this study show that hypothyroid patients have significantly low serum ferritin, serum iron, and transferrin saturation along with elevated total iron-binding capacity (TIBC), implying a high prevalence of iron deficiency. Furthermore, hematological abnormalities like low hemoglobin, microcytosis, and high RDW were prevalent also supporting the association between hypothyroidism and iron-deficiency anemia. Such results are in agreement

with various previous studies [9, 10]. In a similar study, Chatterjee et al. [6] found that ferritin levels were lower in hypothyroid subjects and especially in those with autoimmune thyroiditis, supporting the hypothesis that iron metabolism is disturbed in cases of disruption of thyroid functions. Similarly, Beard et al. [3] found that iron is an essential cofactor for thyroid peroxidase (TPO) functions and its deficiency can impair thyroid hormone synthesis and aggravate hypothyroid symptoms.

We found Serum ferritin has a strong inverse correlation with TSH and a positive correlation with free T4 and hemoglobin, indicating that the severity of hypothyroidism is correlated with more depletion of iron stores. Similar findings were identified by Erdogan et al. [7] reporting that the extent of anemia associated with hypothyroidism is related to the levels of the thyroid hormones. This reaffirms our finding since they respond with lower hemoglobin and higher TSH, patients with low ferritin were found in significantly lower volumes [11]. The results of this study showed that fatigue and pallor clinical manifestations were considerably more in patients with ferritin <30 ng/mL (Table 5). This shows the potential diagnostic utility of ferritin in explaining unresolved fatigue in hypothyroid patients. Das et al. [4] in a similar study showed a correlation between low ferritin with nonspecific symptoms including fatigue in cases with thyroid dysfunction. Hair loss which was common but did not significantly vary by ferritin status, nor did cold intolerance, indicating that both of these symptoms might be more related to the deficiency of hormones rather than the level of iron. Iron deficiency in Hypothyroidism is multifactorial. Lower gastrointestinal motility may affect iron absorption adversely and menorrhagia in females with hypothyroidism may cause chronic blood loss [5, 12]. Additionally, in autoimmune thyroiditis, hepcidin levels can be high due to chronic inflammation, making iron unavailable although iron stores are normal as observed in anemia of chronic disease [13]. The hematological findings of this study of hypochromic anemia in 76% of hypothyroid patients are in agreement with prior studies by Gökdeniz et al.  [14] and Ahmad et al, [15]. The elevated red cell shows that anisocytosis exists in these cases due to iron-deficient erythropoiesis. This pattern can be used to distinguish hypothyroidism-associated anemia from other types of anemia which may be due to chronic disease of vitamin B12 deficiency. Based on these observations it is apt to consider serum ferritin in routine investigations in cases of hypothyroidism. Particularly in cases with fatigue, pallor, or those in whom there is poor response to levothyroxine. Therefore, correction of underlying iron deficiency could enhance the therapeutic efficiency of thyroid hormone replacement as described by Hess et al., [8] who reported improved TPO activity following iron supplementation in hypothyroid animal models.

In conclusion, our study found a significant association between hypothyroidism and altered iron metabolism. Hypothyroid patients had lower serum iron, ferritin, hemoglobin as well as transferrin saturation. There was increased Total iron binding capacity and red cell width. We observed a strong inverse correlation between serum ferritin and TSH levels and patients with lower ferritin levels were having more severe symptoms of fatigue and pallor. Therefore, assessment of serum ferritin in hypothyroid patients could be a valuable tool for early detection and management of iron deficiency which will lead to better treatment response and overall patient outcomes.

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