European Journal of Cardiovascular Medicine

Hypothyroidism is a prevalent endocrine disorder characterized by insufficient production of thyroid hormones, resulting in metabolic and systemic dysfunctions. It affects approximately 4–10% of the general population, with a higher incidence in women and older adults (1). Primary hypothyroidism, commonly caused by autoimmune thyroiditis, iodine deficiency, or post-thyroidectomy status, leads to elevated serum thyroid-stimulating hormone (TSH) and low free thyroxine (T4) levels (2).

Levothyroxine, a synthetic form of T4, remains the standard treatment for hypothyroidism due to its efficacy in restoring normal thyroid hormone levels and alleviating clinical symptoms (3). However, achieving euthyroid status is not always straightforward, as inter-individual variations in absorption, body weight, age, and comorbidities necessitate dose adjustments over time (4). Inappropriate dosing—either over- or under-replacement—may lead to persistent symptoms, adverse metabolic outcomes, and reduced quality of life (QoL) (5).

Quality of life in hypothyroid patients is often impaired due to symptoms such as fatigue, depression, weight gain, and cognitive dysfunction, even when biochemical euthyroidism is attained (6). Therefore, both biochemical control (TSH normalization) and patient-centered outcomes (QoL improvement) are important indicators of successful therapy. Regular follow-up and personalized levothyroxine titration strategies can enhance treatment outcomes, especially during the early months of initiation (7). This study aims to assess the effect of levothyroxine dose titration on serum TSH levels and quality of life in hospital-initiated hypothyroid patients over a 6-month follow-up period.

This prospective, hospital-based observational study was conducted over a period of six months at the Endocrinology Outpatient Department of a tertiary care hospital. Written informed consent was obtained from all participants prior to enrollment.

Study Population:
A total of 60 newly diagnosed adult patients (aged 20–55 years) with primary hypothyroidism were included. Diagnosis was confirmed by elevated serum TSH levels (>10 µIU/mL) with or without low free thyroxine (fT4) values. Exclusion criteria were patients with known thyroid malignancies, pregnancy, secondary hypothyroidism, severe systemic illness, recent thyroid surgery or radioiodine therapy, and those on medications known to affect thyroid function (e.g., amiodarone, lithium).

Intervention and Follow-Up:
All participants were started on oral levothyroxine, with the initial dose calculated based on body weight (approximately 1.6 µg/kg/day). Dose titration was done at intervals of 6 weeks based on serum TSH levels, aiming for a target range of 0.5–4.5 µIU/mL. Patients were followed at baseline, 3 months, and 6 months.

Biochemical Analysis:
Venous blood samples were collected at each visit to measure serum TSH using a chemiluminescent immunoassay. All tests were performed in the hospital's central laboratory, maintaining standard quality control protocols.

Assessment of Quality of Life:
Quality of life was assessed at baseline, 3 months, and 6 months using the Thyroid-Specific Patient-Reported Outcome (ThyPRO) questionnaire. This validated tool includes domains covering physical symptoms, emotional well-being, cognitive function, and social life. Higher scores indicate poorer quality of life.

Statistical Analysis:
Data were analyzed using SPSS version 25.0. Descriptive statistics were used for demographic variables. Paired t-tests and repeated measures ANOVA were applied to compare changes in TSH levels and QoL scores over time. A p-value of <0.05 was considered statistically significant.

A total of 60 patients (48 females and 12 males) with newly diagnosed primary hypothyroidism were included in the study. The mean age of participants was 39.2 ± 9.6 years. Baseline demographic details are shown in Table 1.

Over the six-month follow-up period, a significant reduction in serum TSH levels was observed. The mean TSH level decreased from 18.7 ± 5.4 µIU/mL at baseline to 6.1 ± 2.3 µIU/mL at 3 months, and further to 2.9 ± 1.1 µIU/mL at 6 months (p < 0.001) (Table 2). Most patients (83.3%) achieved TSH values within the target range by the end of the study.

Correspondingly, quality of life, as assessed using the ThyPRO questionnaire, showed marked improvement. The mean total QoL score decreased from 72.4 ± 8.2 at baseline to 48.3 ± 7.5 at 3 months and 31.6 ± 6.4 at 6 months, indicating better perceived well-being over time (p < 0.001) (Table 3).

Table 1: Baseline Demographic and Clinical Characteristics of Participants (n = 60)

Table 2: Mean Serum TSH Levels at Different Time Points

Table 3: Mean ThyPRO Quality of Life Scores over Time

The present study demonstrates that systematic titration of levothyroxine over a 6-month period significantly improves both biochemical and patient-reported outcomes in newly diagnosed hypothyroid patients. The reduction in serum TSH levels and concurrent improvement in quality of life (QoL) support the need for individualized treatment and consistent follow-up during the initiation phase of thyroid hormone replacement.

The findings of our study align with previous reports highlighting that early and appropriate levothyroxine dose adjustment is critical for achieving target TSH levels (1,2). The significant decline in TSH from baseline to 6 months indicates successful restoration of euthyroid status in the majority of patients, consistent with findings from Garber et al. (3) and Jonklaas et al. (4), who emphasized weight-based dosing and periodic monitoring for optimal results.

While biochemical normalization is a primary goal, it does not always correlate with complete symptom relief (5). In our study, quality of life improved progressively over time, which corresponds with research by Saravanan et al. (6) and Wekking et al. (7), suggesting that patients often report residual symptoms even with normalized TSH. The observed QoL improvement, assessed via the ThyPRO tool, reflects better overall well-being and symptom resolution with optimized levothyroxine therapy.

Gender distribution in our study also mirrors global trends, with a predominance of females affected by hypothyroidism (8,9). This could be attributed to autoimmune etiology being more prevalent in women, especially in the middle-aged group (10). Patient adherence and awareness may have also contributed to better treatment outcomes, as previous literature suggests that educational interventions and medication adherence play a crucial role in thyroid disease management (11,12).

Furthermore, our study supports the value of validated disease-specific QoL instruments, such as ThyPRO, which offer better sensitivity to symptom changes compared to generic tools (13). The consistent improvement across follow-up intervals emphasizes the importance of patient-centered monitoring during treatment.

Despite the encouraging results, a few limitations need to be acknowledged. The study was limited by its single-center design and relatively short duration. Long-term follow-up is necessary to assess the sustainability of QoL improvements and the risk of overtreatment or subclinical hyperthyroidism (4). Additionally, comorbidities, psychological factors, and lifestyle variables, which may influence perceived well-being, were not fully accounted for (5).

Overall, the study reinforces the significance of a structured, titration-based approach to levothyroxine therapy. Regular TSH monitoring and use of QoL assessments can guide clinicians in optimizing treatment plans tailored to individual needs.

1. Brigante G, Santi D, Boselli G, Margiotta G, Corleto R, Monzani ML, Craparo A, Locaso M, Sperduti S, Roy N, Casarini L, Trenti T, Tagliavini S, De Santis MC, Roli L, Rochira V, Simoni M. Randomized double-blind placebo-controlled trial on levothyroxine and liothyronine combination therapy in totally thyroidectomized subjects: the LEVOLIO study. Eur J Endocrinol. 2024;190(1):12-22. doi:10.1093/ejendo/lvad172.
2. Okuroglu N, Sakci E, Sertbas M, Sertbas Y, Sancak S, Ozdemir A. Normalisation of serum TSH doesn't represent true euthyroidism for patients on levothyroxine treatment. J Pak Med Assoc. 2022;72(5):827-31. doi:10.47391/JPMA.0588.
3. Lee J, Yun MJ, Nam KH, Chung WY, Soh EY, Park CS. Quality of life and effectiveness comparisons of thyroxine withdrawal, triiodothyronine withdrawal, and recombinant thyroid-stimulating hormone administration for low-dose radioiodine remnant ablation of differentiated thyroid carcinoma. Thyroid. 2010;20(2):173-9. doi:10.1089/thy.2009.0187.
4. Semikov V, Aleksandrov Y, Shulutko A, Mansurova T, Gogokhia T, Gorbacheva A. [Non-surgical aspects of thyroid surgery]. Georgian Med News. 2021;(312):14-22.
5. Lin YS, Yang H, Li XY, Wu LQ, Xu JG, Yang AM, Gao ZR, Ding Y, Zhang YQ, Chen K, Mu ZZ, Jia JM, Niu N, Sun D, Zhang X, Zhang SQ, Geng QQ, Zhang YJ, Chen FN, He BX. Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer: phase I/II study. Eur J Nucl Med Mol Imaging. 2022;49(12):4171-81. doi:10.1007/s00259-022-05865-y.
6. Mithal A, Dharmalingam M, Tewari N. Are patients with primary hypothyroidism in India receiving appropriate thyroxine replacement? An observational study. Indian J Endocrinol Metab. 2014;18(1):83-8. doi:10.4103/2230-8210.126582.
7. Stott DJ, Gussekloo J, Kearney PM, Rodondi N, Westendorp RG, Mooijaart S, et al. Study protocol: Thyroid hormone replacement for untreated older adults with subclinical hypothyroidism—a randomised placebo controlled trial (TRUST). BMC Endocr Disord. 2017;17(1):6. doi:10.1186/s12902-017-0156-8.
8. Hoang TD, Olsen CH, Mai VQ, Clyde PW, Shakir MK. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab. 2013;98(5):1982-90. doi:10.1210/jc.2012-4107.
9. Razvi S, Ryan V, Ingoe L, Pearce SH, Wilkes S. Age-related serum thyroid-stimulating hormone reference range in older patients treated with levothyroxine: a randomized controlled feasibility trial (SORTED 1). Eur Thyroid J. 2020;9(1):40-8. doi:10.1159/000504047.
10. Ko M, Barai R, Brent G. Phosphate binder impairs levothyroxine absorption in a hypothyroid patient with end-stage renal disease. Cureus. 2024;16(10):e71551. doi:10.7759/cureus.71551.
11. Nygaard B, Jensen EW, Kvetny J, Jarløv A, Faber J. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism: a double-blind, randomised cross-over study. Eur J Endocrinol. 2009;161(6):895-902. doi:10.1530/EJE-09-0542.
12. de Keizer B, Brans B, Hoekstra A, Zelissen PM, Koppeschaar HP, Lips CJ, et al. Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy. Eur J Nucl Med Mol Imaging. 2003;30(3):367-73. doi:10.1007/s00259-002-1076-y.

13. Abu-Helalah M, Law MR, Bestwick JP, Monson JP, Wald NJ. A randomized double-blind crossover trial to investigate the efficacy of screening for adult hypothyroidism. J Med Screen. 2010;17(4):164-9. doi:10.1258/jms.2010.010057.