Evaluation of a three-month trial of thyroxine replacement in symptomatic subclinical hypothyroidism: An impact on clinical presentation, quality of life and adoption of long-term therapy

Abstract

Background / Aim. Although subclinical hypothyroidism (SCH) is frequently a biochemical diagnosis, some symptoms and signs of overt disease may be present, influencing our decision to start the treatment with levothyroxine (LT4). The aim of this study was to examine the effect a 3-month LT4 treatment on clinical presentation and quality of life in symptomatic SCH with TSH < 10 mIU/L. We also considered whether treatment discontinuation additionally improves reliability of these findings. Methods. Clinical parameters (disease-specific score) and quality of life (Short Form 36 questionnaire) were measured in 35 patients with persistent symptomatic SCH before the intervention (TSH 7.0±2.1 mIU/L), 3 months after the euthyroid state had been achieved and 3 months after cessation of LT4 substitution. Results. The median of Zulewski index significantly decreased after the treatment with LT4: 5.0 (4.0-7.0) vs 3.0 (2.0-5.0) (p <0.001) representing a reduction of symptoms. The most common ailments before treatment were dry skin (71.4%), hoarseness (65.7%) and rough skin (54.3 %). After the treatment, there was a significant reduction in the frequency of constipation (p=0.004), dry skin (p=0.022), hoarseness (p=0.002), decreased sweating (p=0.006), and delayed Achilles reflex (p=0.002). Quality of life was not changed significantly after LT4 treatment. In the group of 18 patients who discontinued the treatment, many symptoms and signs reappeared with the increasing of TSH (6.8±1.1 mIU/L): periorbital edema, constipation, weight gain, decreased sweating, slow motion and delayed Achilles reflex. The median of the Żulewski index after discontinuation of LT4 was 6.0 (4.0-9.0) (p = 0.010). Also, there was a statistically significant reduction in the general health score, vitality, role emotional and mental health scores. Conclusions. Clinical score based on symptoms and signs is a sensitive and reproducible test for objective estimation of LT4 treatment effects in symptomatic SCH patients with TSH <10 mIU/L and supports individually adjusted treatment. Symptomatic SCH is not necessarily associated with a quality of life impairment that may be significantly improved by thyroxine treatment. Changes in general health, vitality, mental health and emotional role after LT4 cessation suggest that some aspects of life quality can be affected by subtle variations in thyroxine availability.

The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism

“…This is a pilot study within a prospective open-label study [5][6]. Informed consent was obtained from all participants included in the study.…”

“…Whickam survey data registered SCH in 7.5% of women and 2.8% of men, with the highest incidence in women aged over 60 years [2][3]. Although there are controversies about the treatment of SCH, current guidelines clearly suggest a thyroxine replacement trial in individuals aged less than 70 if mild symptoms of hypothyroidism are present, when TSH is between 4.12 and 10 mIU/L [4][5][6].…”

“…Having in mind the pivotal role of thyroid hormones in cardiovascular system function, the adverse effects of SCH on the heart could be expected. According to the literature, diastolic hypertension, coronary heart disease based on accelerated arterial wall thickening and stiffening, endothelial dysfunction and heart failure are clearly linked with SCH, but the beneficial effects of LT4 treatment have not been confirmed [3][4][5][6][7][8][9][10][11][12]. Clarification of the influence of LT4 treatment on cardiovascular risk in SCH would contribute to planning the strategy in cardiovascular prevention for these patients.…”

“…Some studies showed that morphological alterations of the heart, global, as well as systolic and diastolic cardiac dysfunctions and pulmonary hypertension found in SCH were improved after substitutive thyroxine therapy [13][14][15][16]. More recent data underlined measurable differences in some echo parameters when the SCH group was compared to the control group at baseline, and in the SCH group tested before and after thyroxine treatment [6,17]. These findings point to the need for monitoring cardiac morphology and function in individuals with SCH on substitutive therapy in order to provide better objectivity in the assessment of LT4 effects and the rationale for its early introduction.…”

Calculation of left ventricular volumes and systolic indices in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism

“…Considering previous findings, both TSH level and patients' complaints associated with SCH should influence treatment decision. [1][2][3] Biondi et al have shown that even subclinical form of autoimmune thyroid disease impairs cardiac function. 4 Meta-analysis with almost 60 000 participants reported increased risk of fatal and nonfatal events of coronary heart disease, congestive heart failure (HF) and fatal stroke in individuals with higher TSH levels.…”