Available online 20 May 2024

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Teaching Points

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There was a 20% prevalence of Cardiac autonomic neuropathy in euthyroid patients with Graves' disease without evidence of cardiac arrhythmia.

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There were changes in the deep breathing test in 63.3% of patients with Graves' disease, as well as in the Valsalva test in 8.3%, in the orthostatic test in 5% and in the orthostatic hypotension test in 13.3%.

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Smoking was evidenced as a factor associated with the presence of Cardiac autonomic neuropathy, increasing its relationship with conditions that aggravate Graves' disease.

AbstractBackground

Hypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system.

Aims

To characterize Cardiac Autonomic Neuropathy (CAN) as a possible complication in patients with GD.

Methods

We evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients.

Results

60 GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7%, established CAN, while in the control group, it was verified incipient in 8% and established in 6% (p=0.7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of NAC.

Conclusions

The prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.

Section snippetsINTRODUCTION

Graves' disease (GD) represents the etiology of 80% of patients with hyperthyroidism. Excess thyroid hormones lead to a hypermetabolic state that has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system (ANS). Some studies indicate that hyperthyroidism generates symptoms similar to the hyperadrenergic state. The reduction in heart rate in some clinical manifestations induced by β-adrenergic receptor blockers in patients with

Study design and participants

This is a cross-sectional prospective study performed at a specialized tertiary service, in which 60 GD patients, euthyroid, non-diabetic, were evaluated. Individuals in a thyrotoxic state were not included, as this could be a confounding factor when performing CAN tests. Demographic, clinical and disease information, laboratory thyroid function (total T3:TT3, free T4:FT4, thyrotropin:TSH) and blood glucose were obtained. The presence and characteristics of CAN were assessed using autonomic

Descriptive analysis

The demographic, clinical, biochemical, and echocardiographic characteristics of GD patients are described in Table 1. Transthoracic echocardiography was performed in 42 of the 60 patients analyzed. The mean left atrium values were above the reference values 35.7±3.9mm, 11 patients (26%) had pulmonary hypertension and about 50% of the patients had elevated PMAP, above 25 mmHg.

The control group of euthyroid healthy individuals (n=50) was composed of 42 women (84%) and 8 men, with a mean age of

DISCUSSION

The present study demonstrated prevalence of 20% of CAN in euthyroid GD patients, being 13.3% incipient and 6.7% established, highlighting age, and smoking as risk factors for this complication.

CAN is a well-known complication in patients with Diabetes Mellitus, but it remains underdiagnosed (20). The prevalence of CAN is not consensus in the literature, ranging from 1% in HIV (21), up to 53.2% in type 2 Diabetes Mellitus (22), and 20% in healthy individuals (14). The prevalence of CAN in the

Acknowledgements

We acknowledge all patients who voluntarily participated in our study.

We thank Cleide Aparecida Moreira Silva and Marcelo Tavares from the statistical service of the School of Medical Science of University of Campinas.

JVRZ had a Scholarship from São Paulo State Research Support Foundation (FAPESP) (2019/25573-0).

DEZ-W had a National Council of Technological and Scientific Development Scholarship (CNPq) (303068/2021-3).

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© 2024 Published by Elsevier Inc. on behalf of the AACE.