LOW T3 SYNDROME IN CHRONIC HEART FAILURE A CORRELATIONAL STUDY

*Corresponding author: Dr. Monica Razdan Assistant Professor Dept. of Gen. Medicine, Sri Aurobindo Medical College & PG Institute Indore (M.P.)
ISSN: 0976-3031
Research Article
LOW T3 SYNDROME IN CHRONIC HEART FAILURE A CORRELATIONAL STUDY
1Dr. Sonam Verma 2Dr. Monica Razdan, 3Dr. Monam Verma and 4Dr. Bhupendra Chouhan
1Assistant Professor, Dept. of Gen. Medicine, Sri Aurobindo Medical College & PG Institute Indore (M.P.) 2Assistant Professor, Dept. of Gen. Medicine, Sri Aurobindo Medical College & PG Institute Indore (M.P.) 3Postgraduate Student, Dept. of Gen. Medicine, L.N. Medical College And Research Centre Bhopal (M.P.)
4Assistant Professor, Dept. of Gen. Medicine, M.G.M. Medical College Indore (M.P.)
DOI: http://dx.doi.org/10.24327/ijrsr.2020.1106.5396
ARTICLE INFO ABSTRACT
Background-Thyroid abnormalities are common in chronic heart failure. Severity of heart failure rises by several fold in patients with thyroid dysfunction. Objectives-The purpose of this prospective study is to determine the correlation between low T3 syndrome and chronic heart failure & predicting the severity of chronic heart failure Methods-Department of medicine with chronic heart failure during this study period was included. Results- The mean age of low T3 chronic heart failure patients was higher [60.50±6.15(SD) years], Fatigue and generalized weakness, dyspnoea on exertion, swelling of feet, cold intolerance, hair loss, hoarse voice and decrease libido were common symptoms of low T3 chronic heart failure, Alcoholism was higher in patients with low T3 chronic heart failure (80%). Higher number of diabetes mellitus patients were seen in low T3 chronic heart failure (50%). Higher number of hypertensives were seen in low T3 chronic heart failure patients. Cardiomyopathy was most common etiology for chronic heart failure patients (42%) and was common in the age group of 55- 60 years (38%) in present study. Idiopathic etiology was common in the age group of 60-65 years (63%). Hypertensive heart disease as etiology was common with age group of 45-50 years (42.8%).The high pulmonary artery systolic pressure was seen in more number of patients in low T3 chronic heart failure (70%). Conclusion- There is significant percentage of chronic heart failure patients having low T3 alone as biochemical parameter. It is important to recognize this condition in patients with chronic heart failure as it is associated with increased severity of heart failure, increased in evidence of renal failure which may need additional support of thyroid hormone administration to have a better outcome in patients with chronic heart failure.
INTRODUCTION
The cardiovascular system is one of the most important targets on which thyroid hormones act.1,2 More than 80% of the biologically active hormone triiodothyronine (T3) derives from peripheral conversion of prohormone-thyroxine (T4) secreted by the thyroid gland.3 Clinical and experimental evidence has shown that T3 plays a major role in modulating heart rate and cardiac contractility as well as arterial peripheral resistance.1,2 T3 actions are carried out by binding with specific nuclear receptors that regulate responsive genes encoding for structural and functional cardiac proteins; direct, extra nuclear, no transcriptional effects have also been described.1,2
A typical pattern of altered thyroid hormone metabolism characterized by low T3 circulating levels has been described in patients with acute myocardial infarction3,4 and heart failure6
and in adults and children after cardiopulmonary bypass.5–6 The principal pathophysiological mechanism underlying low circulating T3 is the reduced enzyme activity of 5′ monodeiodinase responsible for converting T4 into T3 in peripheral tissues.7,8
This low-T3 syndrome has commonly been interpreted by the medical community as a euthyroid sick syndrome, an adaptive compensatory and thus beneficial response that decreases energy consumption in diseased states.7 This interpretation, however, has recently been questioned. Although clinical data documented the benefit gained from treating patients with synthetic thyroid hormones.9,10. The results suggested that individuals with borderline hypothyroidism may also have similar cardiac changes. Clearly more research is needed to determine if these detrimental cardiac changes occur in humans
Available Online at http://www.recentscientific.com International Journal of
Recent Scientific
Research International Journal of Recent Scientific Research Vol. 11, Issue, 06 (B), pp. 38882-38887, June, 2020
Copyright © Dr. Sonam Verma et al, 2020, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
DOI: 10.24327/IJRSR
Article History:
Received 24th March, 2020 Received in revised form 19th April, 2020 Accepted 25th May, 2020 Published online 28th June, 2020
Key Words:
Chronic heart failure, low T3 syndrome, systolic blood pressure, diastolic blood pressure, global hypokinesia, segmental hypokinesia and PR interval.
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and if treatment of heart patients with borderline hypothyroidism will lead to improved outcomes.11
Objectives of the Study
To determine the patients of chronic heart failure by clinical and investigational methods. To screen the chronic heart failure patients by subjecting them to thyroid profile. To find an association between Low T3 syndrome and chronic heart failure. To determine the severity of cardiac failure in low T3 syndrome patients.
Background
Physiology of Thyroid Hormones13,14
The thyroid gland maintains the level of metabolism in the tissues that is optimal for their normal function. Thyroid hormones stimulate the Oxygen consumption of most of the cells in the body, help regulate lipid and carbohydrate metabolism and are necessary for normal growth and maturation. The principal hormones secreted by the thyroid are thyroxine (T4) and triiodothyronine (T3). T3 is also formed in the peripheral tissues by deiodination of T4. Small amounts of reverse triiodothyronine (RT3) are also found in thyroid venous blood. RT3 is functionally inactive. The thyroid cells sub serve three functions: Iodine Metabolism and Iodine trapping: The principal organs that take up iodine are thyroid, which uses it to make thyroid hormones and kidneys which excrete it in the urine. Ingested iodine is converted to iodide and absorbed. Thyroid hormone synthesis and secretion: In the thyroid gland, due to the action of thyroid peroxidase, iodide is oxidized to iodine and bound in a matter of seconds to 3 position of the tyrosine molecules attached to thyroglobulin. Mono-idotyrosine (MIT) is next iodinated in the 5 position to form diiodo- tryrosine (DIT). Removal of thyroid hormones from thyroglobulin and secretion into the circulation: The thyroid cells ingest colloid by endocytosis.
Fluctuations in Binding: When there is a sudden, sustained increase in the concentration of thyroid binding proteins in the plasma, the concentration of free thyroid hormones falls, followed by increased production of hormones by thyroid gland.
Metabolism of Thyroid Hormones: One third of the circulating T4 is converted to T3 by the action of 5’-deiodinase and 45% is converted into RT3 by 5-deiodinase. 87% of circulating T3 and 95% of circulating RT3 are formed in this way; remaining portion is directly from the thyroid. T4 and T3 are deiodinated in the liver, kidneys and other tissues. In the liver T4 and T3 are conjugated to form sulfates and glucuronoides, which enter the intestine in the bile. They are hydrolyzed in the gut, a part enters into enterohepatic circulation and a part is excreted in the stools. Some T4 and T3 directly enter the gut form the circulation. In total 4% of iodide is lost by these routes and 80% in urine.
Functions of the Thyroid Hormones in the Tissues: The principle effect of the thyroid hormones is to increase the metabolic activities of most of the tissues of the body, with a few notable exceptions like brain, retina, testis, uterus, spleen, lymph nodes and anterior pituitary. The basal metabolic rate can increase to as much as 60 to 100 percent above normal when large quantities of the hormones are secreted. Some of
the widespread effects of thyroid hormones are secondary to stimulation of O2 consumption (calorigenic action); although the hormones also effect growth and development in mammals, help regulate lipid metabolism and increase the absorption of carbohydrates from the intestine.
Thyroid Dysfunctions and Heart Failure: Effects of thyroid hormones on left ventricular contractility, diastolic functions, peripheral resistance, heart rates and cardiac excitability may rarely occur to include cardiac failure in hypothyroid patients. Hypothyroidism may also be the sole cause of heart failure. A low heart rate, decreased myocardial contractility and increased peripheral resistance, can all lead to low cardiac output. Further left ventricular filling may be impaired by the simultaneous presence of left ventricular hypertrophy, abnormal relaxation and bradycardia. Heart failure may occur when peripheral metabolic demand cannot be matched by an adequate cardiac output. Heart failure is however, more common in patients with underlying cardiac disease.15
Clinical Manifestations of Thyroid Hormone Deficiency: The clinical features of hypothyroidism are due to the direct result of under or absent exposure of end organs to the action of thyroid hormones. Almost all the cells in the body have thyroid hormone receptors in their cytosol and respond to thyroid hormones to a greater or lesser degree. Hence most of the symptoms and sign of hypothyroidism are non-specific and can arise from any organ system. In adults, it has insidious onset, diagnosis can be delayed by months or years. Quite often cardiovascular manifestations go unrecognized or subclinical. Individual variations are there; gross deficiency may be associated with only minor clinical features of the disease and vice- versa. Hence a careful history and a high index of suspicious is the key for early diagnosis.
Low T3 Syndrome in Acute and Chronic Illness: Most of the studies on Low T3 Syndrome have been done on people suffering from acute, life-threatening illness. In the intensive care unit, the prevalence of abnormal thyroid function tests is remarkably high. More than 70% of patients show low T3 and around 50% have low T4. Many of these studies have indicated a direct relationship between Low T3 Syndrome the severity and both short- and long-term outcome of disease. The lower the T3 level in critically ill patients, the worse the outcome tends to be. In emotional, psychological or physiological stress, the body will convert excess T4 to reverse T3 (rT3) as a means of conserving energy for healing and repair. It is at least possible; therefore, that replacing thyroid hormone in these cases may not be beneficial. On the other hand, in those suffering from long-term chronic illness, Low T3 Syndrome may be more reflective of pathology than adaptation and this group may benefit from T4 or T3 supplementation16,17.
Treatment of Hypothyroidism18.: Thyroid hormone replacement is the main treatment for hypothyroidism. Today to treat primary or secondary hypothyroidism it is not difficult because of the case and completeness with which it responds to thyroid hormone replacement. Oral levothyroxine is almost always the drug of choice as primary advantages or levothryoxine therapy are its large half life, reliable absorption, normal serum T3 level being achieved with appropriate doses, the peripheral conversion. The initial dose of T4 should be based on the age of the patient, the severity and duration of
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hypothyroidism. Patients under age of 60 yrs with no history of cardiac or respiratory disease can be started on a full replacement dose. 1.6 – 1.8 μg/kg body weight / day. These doses must be taken for 4-8 weeks before their tissue effects and serum T4 and TSH concentration reach a steady state. Bio- availability is not known to be affected by food, it is wise to advise the patient to take their daily dose at the same time in relation to eating every day. Older patients > 60 yrs, require 20-30% less T4/kg. Initially 50μg/day increasing the dose 25 μg at intervals for atleast 6 weeks.
METHODOLOGY
Study Design: Descriptive, prospective study, cross sectional study.
Sample Size: 50 cases over a span of 12 months from November 2018-December 2019 in SAIMS Hospital Indore. Method of Collection of Data: The data for this prospective, descriptive, cross sectional study was collected in a predesigned and pretested proforma which include various socioeconomic parameters like age, sex, occupation, religion, etc. About 50 cases were selected on the basis of the simple random sampling method. The data was statistically analyzed in ANOVA, factor analysis, cross tabs and chi- square test. Inclusion Criteria: Patients with chronic heart failure.
Exclusion Criteria: Included clinical evidence of sepsis or cachexia. Concomitant presence of any predominant severe systemic disease including severe anaemia Hb% < 5g%. 3. Other major surgical procedures performed before or within 6 months after the time of thyroid sampling. Routine investigations to assess thyroid function and to clinically diagnose chronic heart failure.
RESULTS
In this study titled “Low T3 in chronic heart failure- a correlation study” A descriptive, prospective cross sectional study comprising of 50 chronic heart failure patients attending to KR hospital, Mysore who were studied under three groups namely hypothyroid, low T3 and CHF only.
Among 50 chronic heart failure patients 29 patients (58%) are hypothyroid, 10 patients (20%) have low T3 alone and 11 patients (22%) are CHF only in present study.
Table 2 Table showing mean age and duration of symptoms in present study.
Parameter Hypothyroid (n=29) Low T3 (n=10)
CHF Only (n=11) P-Value
Mean Mean Mean
< 0.01 Duration of
symptoms (months) 2.80± 2.24(SD) 3.85±1.63(SD) 5.64± 6.63(SD)
The mean age for low T3 chronic heart failure patients was 60.50 ± 6.15 (SD) years which was higher when compared to
mean age of 59.91± 5.99 (SD) years for CHF only patients and 54.9± 5.49 (SD) years for hypothyroid chronic heart failure patients in the present study which was statistically significant (p< 0.01). The mean age of chronic heart failure patients in the present study was 58.43±5.87 (SD) years.
The mean duration of symptoms in the hypothyroid chronic heart failure patient is 2.80± 2.24(SD) months, mean duration of symptoms in the low T3 chronic heart failure patient was 3.85± 1.63 (SD) months and mean duration of symptoms in chronic heart failure only patient was 5.64± 6.63(SD) months. The duration of symptoms was higher in chronic heart failure only patients when compared to other two groups in the present study which was statistically significant (p< 0.01).
Table 3 Table showing age and sex distribution according to groups in present study
Age groups(yrs)
No. Patients
(n=11) Total (n=50)
45-50 7(14%) Male Female Male Female Male Female Male Female
6 0 0 0 1 0 7 0 50-55 9(18%) 7 0 1 0 0 1 8 1 55-60 16(32%) 5 5 2 1 2 1 9 7 60-65 11(22%) 1 3 1 2 2 2 4 7 65-70 7(14%) 1 1 2 1 1 1 4 3 Total 50 20 9 6 4 6 5 32 18
This table shows that majority of chronic heart failure patients were in the age group of 55-60yrs (32%) followed by 60-65 yrs(22%) and 50-55 yrs (18%) in the present study. Majority of patients (90%) with low T3 chronic heart failure are within the age group of 55-70yrs.
The male: female ratio of patients in the present study was 3.56:2. The male: female ratio of patients’ with hypothyroid chronic heart failure in the present study was 4.4: 2. The male: female ratio of patients with chronic heart failure only in the present study was 2.4: 2. The male: female ratio in patients with low T3 chronic heart failure was 3:2. This shows that male dominance was seen in patients with low T3 chronic heart failure, hypothyroid chronic heart failure and chronic heart failure only groups.
Table 4 Table showing analysis of symptoms of chronic heart failure in the present study
Symptoms
19 (65.52%) 9(90%) 8(72.73%) 36(72%)
Dry skin 1(3.45%) 0(0%) 0(0%) 1(2%) Cold intolerance 1(3.45%) 3(30%) 2(18.18%) 6(12%)
Hair Loss 6(20.69%) 4(40%) 1(9.09%) 11(22%) Dyspnea on exertion 13(44.83%) 10(100%) 3(27.27%) 26(52%)
Weight gain with poor appetite
5(17.24%) 1(10%) 2(18.18%) 8(16%)
PND 10(34.48%) 0(0%) 2(18.18%) 12(24%) Orthopnea 6(20.69%) 1(10%) 6(54.55%) 13(26%)
Hoarse voice 5(17.24%) 3(30%) 4(36.36%) 12(24%) Paresthesias 0(0%) 0(0%) 2(18.18%) 2(4%)
Impaired hearing 1(3.45%) 0(0%) 1(9.09%) 2(4%) Swelling of feet 20(68.97%) 9(90%) 8(72.73%) 37(74%) Puffiness of face 11(37.93%) 2(20%) 4(36.36%) 17(34%) Puffiness of eyes 2(6.90%) 0(0%) 1(9.09%) 3(6%) Decreased Libido 1(3.45%) 2(20%) 0(0%) 3(6%)
Fatigue and generalized weakness was present in 72% of patients with chronic heart failure in the present study. Swelling of feet was present in 74% of patients with chronic
Table 1 Table showing prevalence of hypothyroidism, low T3 and CHF only in present study.
Group Number of patients Percentage (%)
Hypothyroid 29 58
Total 50 100
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heart failure in the present study. Dyspnea on exertion was present in 52% of patients with chronic heart failure in present study. Puffiness of face was present in 34% of patients with chronic heart failure in the present study. Orthopnoea was present in 26% of patients with chronic heart failure in the present study. PND was present in 24% of patients with chronic heart failure in present study. Hoarse voice was present in 24% of chronic heart failure patients in present study. Hair loss was present in 22% of chronic heart failure patients in present study.
Fatigue and generalized weakness was present in 90% of the low T3 chronic heart failure patients when compared to 65.52% in hypothyroid chronic heart failure and 72.73% in patients with chronic heart failure only. Dry skin was seen in 3.45% of patients with hypothyroid chronic heart failure. Cold intolerance was seen in 30% of low T3 chronic heart failure patients when compared to 18.18% in chronic heart failure only and 3.45% of hypothyroid chronic heart failure patients. Hair loss is seen in 40% of low T3 chronic heart failure patients when compared to 20.69% patients of hypothyroid chronic heart failure and 9.09% of chronic heart failure only patients. Dyspnea on exertion was seen in 100% of low T3 chronic heart failure patients when compared to 44.83% hypothyroid chronic heart failure patients and 27.27% in chronic heart failure only patients. PND was seen in 34.48% of hypothyroid chronic heart failure patients, when compared to 18.18% of chronic heart failure only patients and none of low T3 chronic heart failure patients. Orthopnoea was seen in 54.55% chronic heart failure only patients, when compared to 20.69% of hypothyroid chronic heart failure patients and 10% of low T3 chronic heart failure patients. Swelling of feet was seen in 90% of low T3 chronic heart failure patients when compared to 72.73% of chronic heart failure only patients and 68.97% of hypothyroid chronic heart failure patients. Puffiness of face was seen in 37.93% hypothyroid chronic heart failure patients when compared to 36.36% patients of chronic heart failure only patients and 20% of low T3 chronic heart failure patients. Puffiness of eyes was seen in 9.09% of chronic heart failure only patients when compared to 6.90% hypothyroid chronic heart failure patients and none in low T3 chronic heart failure patients. This shows that fatigue and generalized weakness, dyspnea on exertion, swelling of feet, hoarse voice, hair loss, cold intolerance and decreased libido are common symptoms of patient with low T3 chronic heart failure. Orthopnoea, PND and puffiness of eyes were not common symptom in this group of chronic heart failure.
Paraesthesia is seen in 18.18% of chronic heart failure only patients, when compared to none in low T3 and hypothyroid chronic heart failure patients. Impaired hearing was seen in 9.09 % of chronic heart failure patients, when compared to 3.45% of hypothyroid chronic heart failure patients and none of low T3 chronic heart failure patients. Decreased Libido was seen in 20% of low T3 chronic heart failure patients, when compared to 3.45% of hypothyroid chronic heart failure and none of chronic heart failure only patients. Weight gain with poor appetite was seen in 18.18% chronic heart failure only patients,…