European Journal of Cardiovascular Medicine

Thyrotoxicosis (hyperthyroidism) is a condition caused by excessive thyroid hormones (T3, T4, or both), affecting multiple organ systems. It is a common endocrine disorder, occurring in 2% of women and 0.2% of men. Symptoms vary with age, with classical features more prominent in younger patients. The most common cause is Graves' disease (70-80%), followed by thyroiditis, toxic nodular goiter, toxic adenoma, and exogenous hyperthyroidism. Rare causes include TSH-secreting tumors and ectopic thyroxine production.1,2

Thyrotoxicosis presents with symptoms such as nervousness, sweating, heat intolerance, palpitationss, fatigue, weight loss, tachycardia, and frequent bowel movements. Common signs include goiter, tachycardia, widened pulse pressure, tremors, warm moist skin, and eye changes like lid lag and photophobia. Rarely, atrial fibrillation and flutter may occur.3 It affects all age groups, with peak prevalence in puberty and occurrence in the elderly. Symptoms often develop gradually over 3-6 months, leading patients to seek medical attention from various specialists before a thyroid disorders is diagnosed.3-5

Thyrotoxicosis is often diagnosed late despite available medical knowledge. It results from excessive circulating thyroid hormones (T3 and/or T4), leading to a

hypermetabolic state. Hyperthyroidism, primarily caused by Graves’ disease, is a common cause of thyrotoxicosis. However, thyrotoxicosis can also occur without hyperthyroidism, such as in thyroiditis, which causes hormone release due to gland inflammation, or from excessive intake of thyroid hormone supplements like levothyroxine.5

Thyroid hormones regulate metabolism and are essential for normal cellular function. Excess thyroid hormones overstimulate metabolism and the sympathetic nervous system, leading to symptoms like palpitationss, tremors, anxiety, weight loss, and heat intolerance. Common signs include tachycardia, sweating, muscle weakness, irritability, and, in severe cases, psychosis or thyroid storm. Graves' disease is the most common cause of hyperthyroidism, but symptoms vary by age, often resembling normal aging in older adults.6,7 In India, limited studies have detailed the clinical presentation of thyrotoxicosis. Hence, this study aims to assess the clinical profile and etiologies of thyrotoxicosis.

This prospective study was conducted to assess the clinical profile of thyrotoxicosis patients at BJMC Ahmedabad from May 2014 to October 2016. A total of 50 patients of either sex, aged above 12 years, presenting with Patients presenting with hyperthyroid symptoms, signs, or complications—whether admitted or visiting the outpatient department—as well as known cases of hyperthyroidism diagnosed with thyrotoxicosis at our institute, were included in the study. Pregnant hyperthyroid patients, critically ill cases, and patients who did not provide consent for the study were excluded. Each patient underwent a comprehensive general and systemic examination, routine investigations, thyroid function tests, neck ultrasonography, and thyroid scintigraphy as required.

Statistical analysis

The data were collected and entered in Microsoft Excel sheet and then statistically analyzed using SPSS Version 20.0. Continuous variables were expressed as mean ± SD and categorical variables were summarized as frequencies and percentages.

A total of 50 patients were enrolled, with 20% males and 80% females. The mean age was 41.12 years, with 56% of cases in the 12-40 years age group. Additionally, 75% of patients were from urban areas, while 25% were from rural areas as shown in table 1.

Table 1: Age and area distribution of patients of thyrotoxicosis

The most common presenting symptom was palpitationss (90%), followed by increased appetite (86%). Tremulousness of hands, increased sweating, and fatigue/weakness were seen in 84% of patients. Nervousness, weight loss, and dyspnea were present in 80%. Chest pain was the least common symptom (10%), likely related to palpitationss, (figure 1).

The most common sign was warm, moist skin (88%), likely due to the hypermetabolic state associated with thyrotoxicosis. Pallor, hyperreflexia, and hyperactivity were observed in 52%, 46%, and 46% of patients, respectively. Hair loss was seen in 40%, though its exact cause remains unclear. Ocular signs were present in 22%, possibly linked to Graves’ disease. Proximal myopathy was noted in 14%, while onycholysis, pretibial myxedema, and thyroid acropachy were each seen in 4% of patients.

The most common cardiovascular manifestation was palpitationss (90%), followed by dyspnea (80%). Tachycardia was present in 54%, and atrial fibrillation in 14%. Chest pain was the least common (10%), likely related to palpitationss.

Figure 1: Distribution of Thyrotoxicosis patients based on symptoms

Based on the WHO simplified classification of goiter by palpation, 28 out of 50 patients were goitrous. Goiter grading was done according to the WHO simplified classification, with 28% of patients classified as Grade 0, 16% as Grade 1, and 12% as Grade 2, (Table 2).

Out of 28 goitrous patients, 14 had Grade 0 goiter (13 with Graves' disease and 1 with thyroiditis), 8 had Grade 1 goiter (all with Graves' disease), and 6 had Grade 2 goiter (all with toxic multinodular goiter), (Table 2).

Table 2: Distribution of Thyrotoxicosis patients based on goiter grading as per WHO criteria⁸

54% of patients had sinus tachycardia, followed by 32% with a normal pulse rate (60-100/min). The occurrence of atrial fibrillation (14%) and sinus tachycardia (54%) could be attributed to hyperdynamic circulation due to thyrotoxicosis. Hypertension was observed in 18 (36%) patients, of whom 4 were already on antihypertensive treatment.

ECG findings were compared with thyroid profiles, indicating that heart rate and rhythm were directly proportional to increased free T3 and free T4 levels but inversely proportional to TSH levels. Sinus tachycardia was present in 54% of patients, with a mean TSH of 0.03616 IU/ml (max. 0.3917/min. 0.0001), T3 of 9.1196 pg/dl (max. 30/min. 1.5), and T4 of 3.733 ng/ml (max. 30/min. 0.86). Intraventricular conduction disturbances, such as RBBB, were observed in 8% of patients without any other underlying heart disease, (Table 3).

Echocardiographic findings revealed that 32% (16 patients) had pulmonary arterial hypertension (PAH), with mild PAH in 14 (28%) and moderate PAH in 2 (4%) cases. Chamber enlargement was present in 22% of patients, while systolic and diastolic dysfunction were noted in 14% and 12% of patients, respectively. Regurgitant lesions were found in 10%, and 10% had a normal echocardiogram.

          Table 3: ECG Changes among Thyrotoxicosis patients

RVH- Right Ventricular Hypertrophy, LVH-Left Ventricular Hypertrophy, RBBB-Right Bundle Branch Block, PAH-Pulmonary Arterial Hypertension. *(normal range of thyroid profile TSH=0.4- 4IU/ML, FREE-T4=0.7-1.48 ng/dl, FREE-T3=1.71-3.7pg/ml).

In the present study, all 50 patients met the criteria for hyperthyroidism with low TSH levels (<0.4 uIU/ml). Among them, 15 patients had free T3 levels and 12 patients had free T4 levels within the normal range, likely due to ongoing treatment with well-controlled free T3 and free T4 levels. Among the 50 patients with thyrotoxicosis, one patient had a free T3 level below the normal range, which was attributed to being a known case of hyperthyroidism with a history of treatment default and irregular follow-up. Additionally, one patient had a free T4 level below the normal range while maintaining a high free T3 level and low TSH, indicating T3 thyrotoxicosis, (Table 4).

                                       Table 4: Distribution of thyrotoxicosis patients based on thyroid function test.

Thyroid scan was performed in 36 patients, of whom 29 (78.94%) had Graves' disease, 4 (11.11%) had thyroiditis, and 1 patient (2.77%) each had toxic multinodular goiter, solitary toxic nodule, and iatrogenic thyrotoxicosis, (Figure 2).

Figure 2: Distribution of Thyrotoxicosis patients based on radio isotope scan of thyroid.

Anti-TPO antibody testing was performed in 18 patients who opted to get it done externally. Among them, 17 patients tested positive for Anti-TPO antibodies, including 12 patients with Graves' disease and 5 patients with thyroiditis. One patient with toxic multinodular goiter tested negative for Anti-TPO antibodies.

Among 36 patients with Graves' disease, a radioisotope scan was performed in 29 patients, while Anti-TPO antibody testing was done in 12 patients. Among 6 patients with thyroiditis, a radioisotope scan was performed in 4 patients, and Anti-TPO antibody testing was done in 5 patients. Among 6 patients with toxic multinodular goiter, a radioisotope scan and Anti-TPO antibody testing were each performed in 1 patient, with the antibody test being negative. Out of 8 patients with thyrotoxicosis, both radioisotope scanning and Anti-TPO antibody testing were performed in 5 patients with Graves' disease and 3 patients with thyroiditis, (Table 5).

                 Table 5: Distribution of thyrotoxicosis patients as per etiology and investigation.

FNAC was not performed on all patients. It was conducted only in cases where malignancy was suspected, after obtaining consent. Out of 50 patients, FNAC was performed in 10 patients, including 6 with toxic multinodular goiter and 4 with Graves' disease.

In the present study, 72% of patients had Graves' disease, followed by 12% with thyroiditis, 12% with toxic multinodular goiter, 2% with solitary toxic nodules, and 2% with iatrogenic thyrotoxicosis, (Figure 3).

Figure 3: Distribution of Thyrotoxicosis patients based on Etiology.

Most of the thyroid disorders are autoimmune etiology and autoimmune disease are more prevalent in younger age group. In the present study, all patients were within the 12–60 years age group, with no patients above 60 years. The majority (56%) were in the 12–40 years group, and 44% were in the 40–60 years group. The mean age of patients was 41.12 years, ranged from 17 to 60 years. Our findings compared with other studies done by Allan Carle et al.9, Kandan V et al.10 and Allahabadia A et al.11 In the present study female preponderance were seen (80%), which was also observed in previous studies.9,12 The female preponderance could be because of more prevalence of thyroid disorderss in female. 75% of patients were living in urban area, while 25% of patients were living in rural area. There may be two possibilities one is unawareness about thyroid disorderss in rural area and second is our hospital is tertiary care center and getting more urban patients than rural patient. In Allahabadia A et al.11 study, 37.3% of patients had family history of graves‘ disease, while in present study there was no family history of graves‘ disease. Disparity of family history of patients of graves‘ disease could be due to small sample size. 

The most common symptoms observed were tremor (84%), increased sweating (84%), weight loss (80%), nervousness (80%), heat intolerance (78%), and sleep disturbances (66%). Compared to previous studies, Boelaert K et al.13 reported heat intolerance (57.6%), weight loss (57.5%), tremor (54.8%), and nervousness (40.2%), while Limpawattana P et al.12 found weight loss (88%), tremor (57.6%), and sleep disturbances (55.1%). The discrepancies in symptom prevalence may be attributed to differences in study population, sample size, and study duration. Furthermore, the findings of increased sweating (84%), heat intolerance (78%), tremor (84%), and nervousness (80%) in the present study closely align with those reported by Trivelle et al.14 The most common sign was tremors (84%), followed by goiter (56%) and eye signs (22%) in hyperthyroid patients. These findings align with studies by Limpawattana P et al.12 and Boelaert K et al.13.

The most common cardiovascular symptoms observed were palpitationss (90%), followed by dyspnea (80%). Tachycardia was present in 54% of patients, while 14% had an irregular heart rate (atrial fibrillation), likely due to increased circulatory demands and the need to dissipate excess heat from hypermetabolism. Chest pain was the least common symptom, observed in only 10% of patients, and may be associated with palpitationss. These findings are consistent with studies by Kandan V et al.10 and Limpawattana P et al.12. Hypertension was noted in 18 patients (36%) during the study period, with 4 of them already on antihypertensive treatment. The probable cause of hypertension in patients with thyrotoxicosis is the increased circulatory demand due to hypermetabolism and elevated cardiac output, as described by Davies TF et al.15

In the present study, ECG findings correlated with thyroid profiles, showing that heart rate and rhythm were directly proportional to free T3 and T4 levels but inversely proportional to TSH. Sinus tachycardia was observed in

54% of patients (mean TSH: 0.03616 IU/ml, T3: 9.1196 pg/dl, T4: 3.733 ng/ml). Intraventricular conduction disturbances like RBBB were seen in 8% of hyperthyroid patients without other cardiac pathology, consistent with Leo Schamroth's findings.16

In the present study, PAH was measured by 2D echocardiography. A right ventricular systolic pressure above 30 mmHg was considered high. 32% of patients were having high PAH out of those 4% of patients were respiratory cause of PAH (Chronic obstructive lung disease, interstitial lung disease), which was excluded for comparison. The etio pathogenesis of PAH in Thyrotoxicosis patients remains unclear. There are many hypotheses for PAH in hyperthyroid patients, like autoimmune mediated endothelial injury, increased metabolism of nitric oxide by hyperthyroid state, hyperdynamic circulation and decreased surfactant synthesis. 22% of patients had chamber enlargement because of longstanding hyperthyroidism lead to cardiac impairment characterized by low cardiac output, chamber dilation and heart failure like symptoms.17 Systolic and diastolic dysfunction were found in 14% and 12% of Thyrotoxicosis patients respectively. Regurgitant lesion found in 10%. And echo was normal in 10% of patients. These findings are correlated with the study conducted by Kandan V et al.10

All 50 patients met the criteria for hyperthyroidism with low TSH (<0.4 uIU/ml). Among them, 15 patients had normal free T3 levels and 12 had normal free T4 levels due to ongoing treatment. One patient had a free T3 level below normal due to treatment default and irregular follow-up. One patient had low free T4 but elevated free T3 and low TSH, indicating T3 thyrotoxicosis. Anti-TPO antibodies were tested in 25% of Graves’ disease patients due to resource limitations, and all were positive. Compared to Allahabadia A et al.11, where the mean free T3 was 21.5 pmol/l, the present study showed a lower mean free T3 of 11.275 pmol/l, likely due to the smaller sample size. FNAC was performed only in suspected malignancy cases: Out of 50 patients, FNAC was done in 10 (6 with toxic multinodular goiter and 4 with Graves’ disease). All toxic multinodular goiter cases were diagnosed via ultrasound, and FNAC ruled out malignancy. FNAC in Graves' disease confirmed benign diffuse toxic goiter.

The most common cause of thyrotoxicosis was Graves’ disease (72%), followed by toxic multinodular goiter (12%) and thyroiditis (12%), consistent with studies by Allan Carle et al.9 and Javaid F et al.18 Solitary toxic nodules and iatrogenic thyrotoxicosis accounted for 2% each. The rare case of iatrogenic thyrotoxicosis resulted from excessive thyroxine intake in a known hypothyroid patient. Overall, the study confirms that Graves’ disease is the most common cause of thyrotoxicosis, followed by toxic multinodular goiter and thyroiditis.

The present study is limited by its small sample size (50 patients) and being a single-center study, restricting generalizability. Anti-TPO testing was done in only 25% of Graves’ disease patients due to resource constraints, potentially underestimating its prevalence. FNAC was selectively performed in suspected malignancy cases, limiting its broader diagnostic role. Some patients were already on treatment, affecting thyroid function test results. Additionally, the study lacks long-term follow-up, preventing assessment of treatment outcomes and disease progression. Larger, multi-center studies with extended follow-up are needed for more comprehensive findings.

In conclusion, early diagnosis of thyrotoxicosis and its underlying etiology is crucial for timely intervention, which may help in partially or completely reversing the condition. Appropriate treatment strategies can also prevent complications associated with thyrotoxicosis, improving patient outcomes.

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