Correlation exists between serum TSH and doppler echocardiography findings regarding diastolic dysfunction of left ventricle

 

 

Abstract               Problem statement: The heart is affected by thyroid hormone, and it’s could be adverse cardiac effects in thyroid disorder. Thyroid dysfunction itself exists in a wide range – from hyperthyroid state to hypothyroid with subclinical hyperthyroidism and subclinical hypothyroidism in between. Clinically, apparent illness in the extreme two disorders can easily seek medical attention. The problem exists in dealing with the subclinical dysfunctions. Methods: Patients were admitted in the department of Medicine. And all the biochemical parameters have been done in the department of Biochemistry. in M.G.M Medical College and L.S.K. Hospital. One hundred and fifteen patients were selected from our Medicine outdoor and indoor medical wards. After selection they were evaluated by Doppler echocardiography study. Among 115 patients, 50 patients were found to have Echo-doppler criteria of left ventricular diastolic dysfunction. These 50 patients were finally selected for the study. It was case and control study. Result: One hundred and fifteen patients with overt hypothyroidism were studied by echo doppler, among which fifty patients with Echo Doppler criteria of left ventricular diastolic dysfunction were finally selected for our study. We lost follow- up of 8 patients during our study before the first assessment. Fifty age and sex matched normal persons served as a control group. Mean age of our study group was 38.52 + 5.08 years. Serum TSH level showed a significant decrease in our patients from 51.33 + 30(m Iu/L) to 4.41 + 1.7 (mIu/L) after 3 months of L- thyroxine therapy. Serum T3 and T4 showed a significant rise in our patients from 0.85 + 0.84 (nmol/L) to 2.14 + 0.61 (nmol/L) and 43.64 + 16.37 (nmol/L) to 92.13 + 18.35 (nmol/L). Conclusion: The probable mechanism of improvement of left ventricular diastolic dysfunction in the early part of thyroxine replacement therapy was due to biochemical changes i.e. induction of calcium ATPase by L-thyroxine in sarcoplasmic reticulum of myocardial cells. The subsequent improvement in the overall diastolic function of left ventricle was possibly related to continued biochemical and associated structural changes in the myocardium. However a long term follow-up is required in this aspect.

Key Word: hypothyroidism, hyperthyroidism, left ventricular diastolic dysfunction, L-thyroxine

 

 

 

 

 

INTRODUCTION

The cardiac manifestations in primary hypothyroidism are of mainly systolic dysfunction^1. Because of adverse cardiovascular effect of hypothyroidism has been identified in many studies. Most of the studies focused on systolic/diastolic dysfunction in hypothyroidism^2- 6. Early identification of patients with sub-clinical hypothyroidism may lead to early treatment and thereby favourable effect on cardiovascular morbidity and mortality. A number of studies have demonstrated cardiac problems in both subclinical hyperthyroidism and subclinical hypothyroidism. There is an increased resting heart rate; supravenrticular arrhythmias, diastolic dysfunction, and increased left ventricular mass are some of the established cardiological manifestations of subclinical hyperthyroidism.^8,9 Subclinical hypothyroidism is defined as variable increase in serum thyroid stimulating hormone (TSH) concentration with apparently normal serum free T4 and free T3 levels.¹⁰ Prevalence of subclinical hypothyroidism is about 10% among individuals over age 60 years, with a higher prevalence in women.¹⁰ According to some literature, it is associated with left ventricular diastolic dysfunction and may also lead to exercise intolerance and diastolic heart failure or atherosclerosis.^11-14 Doppler echocardiography has been used extensively to evaluate left ventricular systolic and diastolic function in patients with subclinical hypothyroidism. Alterations of left ventricular diastolic function, indications by a prolonged isovolumetric relaxation time (IVRT), and abnormal time-to-peak filling rate are the most common association reported.¹¹ On the other hand, some authors clearly deny any association of cardiac dysfunction in subclinical hypothyroidism.^15-16 That is why, there is no established guideline regarding treatment plan of these patients. Some favor treatment with levothyroxine whereas others disagree. Because of this dilemma, the study was conducted to find out whether cardiac function exists in subclinical hypothyroid patients and establish a clear relationship between left ventricular diastolic function and subclinical hypothyroid Indian patients.

Diastolic dysfunction: Diastolic dysfunction itself often does not cause any symptoms. However, if the problem progresses to the point that it starts to affect other organs and body parts, diastolic heart failure is diagnosed. In those situations common symptoms include:

• Difficulty breathing and shortness of breath. Initially, this may only occur when exercising, but as the illness progresses, breathing can become problematic during any activity, including resting or lying down.
• Unusual weight gain or swelling (edema) in the ankles, legs and abdomen.
• Irregular or rapid heartbeat.

Primary hypothyroidism: Primary hypothyroidism is a common medical problem occurring in approximately 1 to 3% of the total population, with an annual incidence rate of 1 to 2 in 1000, in females; and 2 in 10000 in males.¹⁷ The clinical presentation of hypothyroidism in young patients is well detailed in classical medical textbooks.¹⁸ Overt hypothyroidism is associated with typical symptoms and signs such as the slowing of motor activity, constipation, cold intolerance, menorrhagia, stiff muscles, sleep apnea, dry skin, weight gain, snoring, and a hoarse voice.¹⁸ Less common symptoms involve the heart, muscle, joints, and blood.¹⁹ Rai highlighted the fact that the well-known signs and symptoms of hypothyroidism in older patients reported in textbooks are uncommon.²⁰ The objective of this study was to find out the similarity of the symptomatology of hypothyroidism in all age groups to the typical ones reported in the medical textbooks.

The relationship of thyroid hormonal abnormalities and cardiovascular disease: The relationship of thyroid hormonal abnormalities and cardiovascular disease goes well beyond the risk of atherosclerosis in association with hypothyroidism and the risk of atrial fibrillation in persons with hyperthyroidism.²¹ The two organ systems are intimately linked by their embryological anlage, and the ubiquitous effects of thyroid hormone on the major components of the entire circulatory system: the heart, the blood vessels and the blood as defined by the flow law.²² Cardiac output is normally modulated by peripheral arteriolar vasoconstriction and dilatation, venous capacitance, and blood volume in response to tissue metabolic needs.²³ The heart can only pump the blood that returns to it, so factors that influence venous return such as blood volume and venous capacitance are critical. Arteriolar dilatation reduces peripheral vascular resistance and thus afterload, increasing cardiac output. The four key issues to be emphasized in this review include a discussion of the normal effects of thyroid hormone on cardiovascular function, as well as therapeutic strategies designed to manage coronary artery disease, atrial fibrillation and heart failure when thyroid hormonal dysfunction is present.

 METHODS

Study Area: Department of Medicine and Biochemistry, M.G.M Medical College and L.S.K. H ospital, Kishanganj, Bihar.

Study Population: Patients were admitted in the department of Medicine. And all the biochemical parameters have been done in the department of Biochemistry. in M.G.M Medical College and L.S.K. Hospital

Study Period: January 2017 to February 2018.

Sample Size: 50 patients at least.

Selection of hypothyroid patients

Patients were initially selected on the basis of clinical suspicion. They were then subjected to thyroid function test (serum T3, T4, TSH estimation). Elevated TSH was the prime criterion in the diagnosis of hypothyroidism (serum TSH>6 mIU/L).²³ One hundred and fifteen patients were selected from our Medicine outdoor and indoor medical wards of M.G.M Medical College and L.S.K. Hospital, Kishanganj, Bihar. After selection they were evaluated by Doppler echocardiography study. Among 115 patients, 50 patients were found to have Echo-doppler criteria of left ventricular diastolic dysfunction. These 50 patients were finally selected for the study. Left ventricular diastolic dysfunction was considered when; (Echodoppler criteria)

• E_max (early diastolic filling velocity of mitral valve) was decreased compared to A_max (Late diastolic filling velocity of mitral valve) i.e, E_max<A_max and their ratio E/Amax is less²³ than one (E/A =1.7+/-0.6,normal range)
• Mitral E wave decleration time (peak of E wave to end of E wave, i.e, DT) and Isovolumic relaxation time(IVRT) with higher than normal values also reflected diastolic dysfunction.(DT=184+/-24msec, IVRT=74+/-26msec,normal range) ²⁴.

Follow – up: After treatment with L-thyroxine, the same patients were assessed after 3 weeks and 3 months in respect of clinical signs and symptoms, electrocardiographic assessment, serum thyroid hormones level and Doppler echocardiographic assessment and serum triglyceride and cholesterol level. Mean dose of L-Thyroxine was 76.5 + 27.39 mcg.

 

RESULTS

Table 1: Age and Sex wise distribution in case group

 

Table 2: Age and sex distribution in control group

Out of the 50 hypothyroid patients with left ventricular diastolic dysfunction, we lost follow-up of 8 patients during our study before the first assessment.

 

Table 3: Signs in hypothyroid patients before and after 3 months of treatment with L-thyroxine

Compares the signs of hypothyroid patients before and after 3 months of treatment with L-thyroxine. It shows that periorbital puffiness was the commonest sign(62%), followed by delayed ankle jerk in 50%,alopecia in 40%, bradycardia in 20% and CTS in 18% of patients. Goitre was observed in 4% of patients. Raised JVP (jugular venous pressure), gallop and enlarged liver were found in none of the patients. All the signs resolved after treatment except periorbital puffiness, alopecia and goiter which persisted in 16.66%, 16.66% and 4.76% of patients respectively.

Table 4: Change in body weight after 3 months of treatment of hypothyroid patients with L-thyroxine

compares the mean body weight of hypothyroid patients before and after treatment. There was a significant reduction in body weight (p<0.01) after 3 months of treatment, no significant reduction in body weight was seen after 3 weeks of treatment.

Table 5: Change in pulse rate after 3 months of treatment of hypothyroid patients with L-thyroxine

Compares the pulse rate of hypothyroid patients before and after treatment. No significant reduction in pulse rate was observed after 3 months of treatment.

Table 6: Change in Serum Thyroid hormone levels before and after treatment of hypothyroid patients with L-thyroxine

Serum Thyroid Hormone level	Before treatment (n=50)		After 3 weeks of treatment (n=42)		p value of change
	Mean	±SD	Mean	±SD
T3 (nmol/L)	0.85	+ 0.48	1.10	+ 0.41	p< 0.01 (S)
T4 (nmol/L)	43.64	+ 16.37	52.12	+ 14.73	p< 0.01 (S)
TSH (miu/L)	51.33	+ 30.00	44.90	+ 25.19	p> 0.05 (NS)

 

Table 7: Change in Serum Thyroid hormone levels before and after treatment of hypothyroid patients with L-thyroxine

Compares change in serum thyroid hormone levels in hypothyroid patients before and after treatment. Significant rise was observed in serum T3 level after 3 weeks and 3 months of treatment, from 0.85 + 0.48 to 1.10+ 0.41 and 2.14+ 0.62 respectively. Serum T4 level also showed significant rise after 3 weeks and 3 months of treatment with L-thyroxine from 43.64 + 16.37 to 52.12+ 14.73 and 92.13+ 18.35 respectively. Serum TSH level did not show a significant decrease after 3 weeks of treatment (44.90+ 25.19, P>0.05), but a significant decrease was seen after 3 months of treatment with L-thyroxine from 51.33 + 30.00 to 4.41+ 1.70.

Table 8: Comparison of left ventricular dimensions in hypothyroid patients before and after L-thyroxine therapy

 

Table 9: Comparison of left ventricular dimensions in hypothyroid patients before and after L-thyroxine therapy

Reveals that after 3 weeks of treatment of hypothyroid patients, there was no significant decrease in LVEDD, IVST, LVPWT or in IVST/LVPWT ratio. But after 3 months of treatment a significant decrease was found in all the aforesaid parameters; LVEDD decreased from 44 + 4.58 to 40.36 + 4.96, IVST decreased from 12.38 + 3.43 to 8.62 + 1.65, simultaneously LVPWT showed a decrease from 10.64 + 1.77 to 9.52 + 1.71. A significant decrease was also observed in the IVST/LVPWT ratio from 1.15 + 0.16 to 0.89 +0.052. On the other hand, ejection fraction percentage did not show any significant increase after 3 months of treatment.

 

DISCUSSION

One hundred and fifteen patients with overt hypothyroidism were studied by echo doppler, among which fifty patients with Echo Doppler criteria of left ventricular diastolic dysfunction were finally selected for our study. We lost follow- up of 8 patients during our study before the first assessment. Fifty age and sex matched normal persons served as a control group. Mean age of our study group was 38.52 + 5.08 years. We noted various signs and symptoms in these 50 overt hypothyroid patients. Dry skin was the commonest symptom, found in 88% consistent with the findings of Wayne ²⁵, who found it in 90%. Cold intolerance was noted in 82%, comparable with E. J. Wayne’s ⁴⁷ findings, who found it in 95% and Chatrchai et al²⁶, who found it in 58% of cases. Fatigue was found in 74% of our cases, consistent with the findings of Wayne⁷⁶, who found it in 90% and Chatrchai et al²⁷ who found it in 69% Weight gain was seen in 70% of our patients compared to 60% of cases as observed by Wayne⁴⁷ and 47% of cases as noted by Chatrchai et al²⁶ in their study. Hoarseness of voice was found in 50% of our cases comparable with the findings of Chatrchai et al²⁷, who found it in 50%. Alopecia was observed in 40% of our patients which is consistent with the findings of Chatrchai et al²⁵ who found it in 34% of cases. Dyspnoea was found in none of our patients compared to 10% of cases as observed by Chatrchai et al²⁶. Constipation was found in 26% of our cases, compared to 54% of cases in E. J. Wayne’s²⁵ study. Menorrhagia was found in 22% of our cases compared to 15% of cases, as studied by Chatrchai et al²⁸. Periorbital puffiness was observed in 62% of our patients which is consistent with the findings of E. J. Wayne who found it in 57% and Chatrchai et al⁷⁶ who found it in 65% of patients. Delayed anklejerk was observed in 50% of our patients consistent with the findings of Chatrchai et al²⁶ who found it in 43.5% of cases. Serum TSH level showed a significant decrease in our patients from 51.33 + 30(m Iu/L) to 4.41 + 1.7 (mIu/L) after 3 months of L- thyroxine therapy. Serum T₃ and T₄ showed a significant rise in our patients from 0.85 + 0.84 (Nmol/L) to 2.14 + 0.61 (nmol/L) and 43.64 + 16.37 (Nmol/L) to 92.13 + 18.35 (Nmol/L) respectively after 3 months of treatment. Our age group varied from 30-48 years (mean age 38.52 + 5.08 years). We did not observe any significant correlation between E_max, A_max, E/A_max ratio, IVRT, DT and pulse rate, neither between E/A_max ratio and age (in years). Diastolic dysfunction of left ventricle in the pre-treatment hypothyroid patients was evident by significantly decreased early diastolic filling velocity of mitral valve (E_max) (60.14+ 8.12 m/sec) compared to significant increase in late diastolic filling velocity of mitral valve- Amax (79.40 + 11.21 cm/sec) and E/A_max ratio of less than one compared to control group. Also isovolumic relaxation time- IVRT (95.50 + 5.92 msec) and mitral E wave deceleration time- DT (237. 26 + 14.33) were found to be significantly increased in our patients, compared to control group, signifying diastolic dysfunction. Our findings were consistent with that of V. K. Virtamen et al²⁹, who found decreased E_max, increased Amax, E/A_max ratio of less than one, increased IVRT and DT in hypothyroid patients before treatment. Regarding left ventricular dimensions, interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), IVST /LWPWT ratio and left ventricular end diastolic diameter (LVEDD) were found increased in the hypothyroid patients before treatment, when compared to control group. V. K. Virtanen et al²⁸ and Verma et al³⁰, found a similar increase in IVST and LVPWT value, but didn’t find an increase in LVEDD value. Asymmetric septal hypertrophy (IVST/LVPWT ratio>1.3) was found in 26% of our patients before treatment, consistent with the findings of Zia Q Farooki et al³, while concentric hypertrophy (IVST/LVPWT ratio>1) was found in 34% of our patients consistent with the findings of Gupta et al³² who found it in 30% of cases.

 

CONCLUSION

Out of one hundred and fifteen hypothyroid patients, fifty patients were selected for our study who had echo Doppler evidence of left ventricular diastolic dysfunction. Apart from hypothyroidism there were no other cause to account for their diastolic dysfunction. Improvement in the left ventricular diastolic function following L-thyroxine replacement therapy was observed in all the patients during follow-up. The earliest improvement was seen in E_max, at 3 weeks of therapy (increased from 60.14 + 8.12 cm/sec to 62.02 + 6.08 cm/sec)- suggesting that early diastolic filling velocity of mitral valve is corrected first following replacement therapy. After 3 months of treatment along with an increase in E_max there was a significant decrease in A_max i.e. late diastolic filling velocity of mitral valve (from 79.40 + 11.21 cm/sec to 63.76 + 10.12 cm/sec), leading to an increase in E/A _max ratio from 0.7498 + 0.084 to 1.21 + 0.10. This signified a reversal of the diastolic dysfunction of the left ventricle. There was also a decrease in isovolumic relaxation time from 95.50 + 5.92 to 83.09 + 6.04 msec (IVRT) and decleration time of mitral E wave (DT) from 237.26 + 14.33 msec to 213.8 + 10.68 msec – indicating an overall improvement in the diastolic function of the left ventricle. We also found a significant decrease in left ventricular end diastolic diameter (LVEDD), inter ventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) and IVST/LVPWT ratio after 3 months of therapy- suggesting structural changes of left ventricle.

 

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