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Health Problems Accompanying Hypothyroidism in Patients in Ecuador

Universidad Central del Ecuador, Hospital Docente “Carlos Andrade Marín”, Unidad de Prevención e Investigación Neuroendocrinovascular,

*ESPOL Polytechnic University. Escuela Superior Politécnica del Litoral, ESPOL. CIBE y FCV. Campus Gustavo Galindo,

**Universidad Católica de Santiago de Guayaquil. Instituto de Biomedicina. Facultad de Ciencias Médicas. Guayaquil, Ecuador

Purpose: The thyroid gland regulates a range of physiological functions through its hormonal secretions and multiple metabolic dysfunc- tions can arise from its functional anomalies. In this paper, the correlation between hypothyroidism (HT) and other diseases with particu- lar emphasis on vascular risks have been studied.

Materials and Methods: Out of 11,520 adult patients who received medical care in external consultation of a public clinic of the Ecuadorian Institute of Social Security and in the Private Unit of Prevention Neuro-endocrine-vascular of Quito (Neurosciences Institute), 645 patients di- agnosed with HT were studied.

Results: As compared to the general population, there was a signicantly higher frequency of the following diseases among HT patients: dyslipidemia (67.0% vs. 1.4%), arterial hypertension (36.0% vs. 9.3%), obesity (35.0% vs. 24.3%), and hyperglycemia (18.0% vs. 3.4%). HT patients also exhibited various health hazards like cardiomegaly (18%), stroke (17%), and acute myocardial infarction (9%). Primary HT ex- hibits an incidence index with higher occurrences in the women (75.0%).

Conclusion: This study proposes, to this Hospital and the Ecuadorian Government, the implementation of greater effort in the diagnosis and research of root causes of HT in favor of prevention, and not just the control of co-morbidities, with the aim of enhancing the quality of life and prognosis for patients.

Keywords: Hypothyroidism, vascular risks, dyslipidemia, arterial hypertension, obesity, hyperglycemia

Amaç: Tiroid bezi hormonal sekresyonlarla çeşitli zyolojik fonksiyonları düzenler ve fonksiyonel anomalilerinden çoklu metabolik fonksi- yon bozuklukları ortaya çıkabilir. Bu yazıda, hipotirodizim (HT) ile diğer hastalıklar -özellikle vasküler riskler üzerine odaklanılarak- arasın- daki korelasyon çalışılmıştır.

Gereç ve Yöntemler: Ekvador Sosyal Güvenlik Enstitüsü kamu kliniği ve Quito (Nörobilim Enstitüsü) Nöro-endokrin-vasküler Önleme Özel Biriminde dışardan konsülte edilerek tıbbi bakım alan 11.520 erişkin hasta arasından HT tanısı alan 645 hasta çalışmaya alınmıştır.

Bulgular: Genel popülasyona kıyasla, HT hastalarında aşağıdaki hastalıkların görülme sıklığı anlamlı şekilde daha yüksektir: dislipidemi (%67,0’a karşı %1,4), arteriyel hipertansiyon (%36,0’a karşı %9,3), obezite (%35,0’a karşı %24,3) ve hiperglisemi (%18,0’a karşı %3,4). HT has- talarında ayrıca kardiyomegali (%18), inme (%17) ve akut miyokard infarktüsü (%9) gibi çeşitli sağlık riskleri de görülmüştür. Primer HT, ka- dınlarda daha yüksek oranlarda insidans indeksi sergilemektedir (%75,0).

Sonuç: Bu çalışma, bu hastaneye ve Ekvador hükümetine, hastaların yaşam kalitesini ve prognozunu iyileştirmek amacıyla yalnızca eşlik eden hastalıkların kontrolünü değil, HT’nin önlenmesi için temel nedenlerinin teşhisi ve araştırılmasına yönelik daha fazla çaba gösteril- mesini önermektedir.

Introduction

The thyroid gland hormonally regulates a broad spectrum of meta- bolic functions, and alterations in the thyroid gland are associated with pathologies that have a high prevalence in the population worldwide (1). Morbidities such as cardiovascular risks, lipid profile alteration, and obesity are found to be much higher in patients with

clinical HT (2–5). Even an association of HT with diabetes mellitus has been reported (6,7). A complete removal of the thyroid gland leads to accelerated atherosclerosis in rats, while humans com- monly develop hypertension and dyslipidemia after thyroidectomy (8,9). The focus of most medical practices on the unilateral man- agement of metabolic syndromes such as hypertension, dyslipi- demia, and hyperglycemia, without a thorough investigation of the underlying pathogenic cause, seems to lead to an under-diagno- sis of HT (10–14). The present study focuses on a comprehensive analysis of diseases accompanied and perhaps caused by a dys- functional thyroid gland.

Methods

This study was carried out in two hospitals in Quito (Ecuador), an area that has low levels of natural iodine in the environment that drastically increases the incidence of HT (15,16). The percentages of different metabolic/vascular diseases were stratified by gender and age.

Totally, 11,520 adult patients were analyzed over a period of seven years at the Carlos Andrade Marín Hospital of the Institute of So- cial Security and at the Private Unit of Prevention Neuro-endocrine- vascular of Quito (Neurosciences Institute).

HT was confirmed with thyrotropin (TSH) and free thyroxine (FT4) measurement with Electrochemiluminescence Immunoassay (ECLIA) using ECLusys FT4 and TSH Kits (Roche Diagnostics GmbH, Mannheim, Germany). The following values of the thyroid hor- mones for adults were used as a baseline for indexing health sta- tus: FT4, 0.8-1.6 ng/dL; TSH, 0.2-4.5 µU/mL. The incidences of elevated TSH and low FT4 levels were considered an indication of HT.

The coincidences of dyslipidemia, hypertension, obesity, hyper- glycemia, cardiomegaly, cardiovascular disease, and myocardial infarction, along with HT were determined. These data were strat- ified by gender and ranged groups of ten years for age, from 20 to 89 years old.

Obesity was defined as a body mass index (BMI) equal to or greater than 30 kg/m2. Blood pressure was measured using a manual sphygmomanometer to confirm the presence of hyper- tension (defined as systolic pressure higher than 140 mmHg or a diastolic pressure higher than 90-99 mmHg). Pre-prandial labora- tory tests were done for glucose, lipid profile, uric acid, and serum electrolytes. A baseline fasting blood glucose concentration of ≥7 mmol/L was considered as an indicator of hyperglycemia. Dyslipi- demia was determined by an incidence of higher serum levels of total cholesterol, triglycerides, and LDL recorded at greater than the 90th percentile, and lower levels of HDL below the 10th percentile. Depending on the presence of symptoms, nuclear magnetic reso- nance (NMR) was performed with a Siemens Magnetom Sym- phony 1.5T®, in axial, coronal, and sagittal planes, to detect cerebrovascular diseases. Teleradiographies (X-ray images) for de- tecting cardiomegaly, were all taken in the posteroanterior posi- tion and were recorded, either with the Shimadzu Flexavision F3 package, using an X-ray tube (400 KHU) in the initial phases of the study, or later with a Siemens Vertix digital radiography system, with X-ray tube assembly Optilix 150/30/50 C.

Additionally, the medical history of these patients was studied to determine the incidence of neuropathy, depression, bradypsychia, gout disease, constipation, insomnia, and endocrine anemia. The patients diagnosed with HT were prescribed replacement therapy with synthetic thyroxine (T4) with initial doses being carefully se- lected on the basis of the patient’s weight, age, and accompany- ing medical conditions.

Statistical analysis

The statistical evaluation of the data was performed by Student’s t-test and a chi-Square test, using a significance level of 0.05. This study was conducted with the informed consent of the patients and their families and with meticulous care taken to keep patient in- formation confidential.

Results

Prevalence of HT

The sample of patients with a clinical diagnosis of HT was made up of 645 people, representing the 5.60% of all patients registered with a higher incidence among women (7.50% vs. 3.18%; p<0.05). Chronic autoimmune thyroiditis was the most common underlying etiology of HT (65%) followed by the environmental iodine defi- ciency (22%), and drug-induced inhibition of production of thyroid hormones (1%).

Relationship with other diseases

The HT patients presented with significantly higher rates (p<0.05) of dyslipidemia, arterial hypertension, obesity, and hyperglycemia. Dyslipidemia was observed in 67.0% of patients compared to 1.4% of the total Ecuadorian population (17). Thirty-six percent of the HT patients exhibited arterial hypertension, compared to 9.3% in the general population (18), and 35.0% exhibited a higher obesity ratio, compared to 24.3% (19). Hyperglycemia was recorded in 18% vs. 3.4% in the general population (20).

The HT patients presented with various cardiovascular diseases: cardiomegaly (18%), stroke (17%), and acute myocardial infarction (9%) (Table 1). Sixty-two percent of the HT patients demonstrated all three symptoms: dyslipidemia, hyperglycemia, and hypertension. The patients were stratified in 10-year exclusive ranges beginning from the age of 20. The details of patients depicting stratification based on age intervals are presented in Tables 2 and 3. Dyslipi- demia, high blood pressure and hyperglycemia, and obesity were more common in the 50-79 years, 60-69 years, and 70-79 years groups, respectively.

Other co-morbidities associated with HT in patients were as fol- lows: neuropathy (23%), depression (64%), bradypsychia (13%), gout disease (11%), constipation (9%), insomnia (7%), and endocrine anemia (5%). After substitution treatment with synthetic T4, the TSH levels in all HT patients increased to >0.2 µU/mL

 

Discussion

An analysis of accompanying health problems in the HT patients in a population of the Andes (Quito, Ecuador) was made in this lon- gitudinal study. In this area, owing to a low level of environmental iodine (EI), the population exhibits a high incidence of HT (5.6%), with the incidence being two times higher in women than in men. The higher incidence of HT in women may be due to a decrease in the estrogenic vascular protection post 45 years of age (21). How- ever, an age range over 80 years did not show any difference be- tween genders; this may be due to the underlying autoimmune mechanisms for most types of thyroid diseases (3).

A possible explanation for the correlation between HT and dyslipi- demia is that HT causes alterations in the composition and trans- port of lipoproteins, as well as the lipids synthesis and metabolism (2–4). HT is also associated with hypercholesterolemia, due to an increase in the level of total and LDL (low-density lipoprotein) cho- lesterol, ApoB (apolipoprotein B), and possibly triglycerides con- centration (22).

As depicted by the results, higher rates of hypertension were found among HT patients than in the general population. In fact, a direct relation between systolic (but not diastolic) blood pressure and the level of triiodothyronine in the blood (23) is documented in HT pa- tients in other studies.

In this study, HT patients showed a higher rate of obesity than the general population. The deficiency of thyroid hormones, known modulators of adaptive thermogenesis, may lead to an increase in the body weight due to the growth of mucin deposits and water and salt retention (24). However, it is still unclear that which is the cause and which is the effect, since it also known that extreme obesity leads to an increase in TSH due to an abnormality in the hy- pothalamic-pituitary-thyroid axis (5).

The higher prevalence of hyperglycemia among HT patients could be because both diseases share susceptible causal genes and co- exist with other organ-specific autoimmune diseases. Therefore, a thyroidal dysfunction should compromise metabolic control, com- pounding the risk of cardiovascular diseases in diabetic patients (25).

A high prevalence of cardiovascular diseases in HT patients is con- sistent with the fact that one of the most characteristic symptoms to detect HT is related to the effect of the thyroid hormone on the cardiovascular system (26) and stroke (27). This effect of HT on the cardiovascular system is related to cardiac output, cardiac con- tractility, myocardial oxygen consumption, variation in blood pres- sure, and systemic vascular resistance (28), and may even induce atrial fibrillation.

A timely management of HT could lead to an improved quality of life in the patients suffering from different related diseases like

Turk J Endocrinol Metab  Cevallos et al.
Hypothyroid Patients in the Ecuadorian Population stroke and accelerated atherosclerosis. Improving myocardial con- tractility could thus lead to the vascular recovery and reduce the risk of acute myocardial infarction. Dyslipidemia could also be con- trolled with the management of HT, boosting this hypertension cure and reducing the risk of other co-morbidities (1,18). A major prob- lem with the diagnosis of HT is that it is often not obvious and re- quires a high degree of suspicion. To make a correct diagnosis the determination of TSH is required since there are no specific clinical manifestations or pathognomonic signs associated with this dis- order. This determination is necessary when patients show symp- toms suggestive of HT, such as constipation, fatigue, dry skin, hoarseness, muscle weakness, etc.

The high prevalence of HT in Latin America, mostly under-diag- nosed, must prompt both government and private health man- agement institutions to undertake all types of training campaigns for their medical personnel to implement new clinical measures. It should involve third generation laboratory tests, as in the case of the “Equinoccial” scale used in the clinical phase of this study. Global health policies are generally directed toward the control of pre- ventable risk factors, and not their elimination. A significant ad- vancement in the neuroendocrine-metabolic pathogenic research is required, which could be more effective in reducing vascular mor- bidity-mortalities and disabilities arising from cerebral infarctions. An improved coverage of the control of hypertension, hyper- glycemia, dyslipidemia, and smoking is not enough; efforts need to be made to reduce stroke-induced mortality for which the socioe- conomic cost is among the highest of all chronic diseases (29).

In conclusion, this study proposes, to this Hospital and the Ecuado- rian Government, the implementation of greater effort in the diag- nosis and research of root causes of HT in favor of prevention, and not just the control of co-morbidities, with the aim of enhancing the quality of life and prognosis for patients.

Author Contributions

Idea/Concept: Óscar Luís Vaca Cevallos; Design: Óscar Luís Vaca Cevallos; Control/Supervision: Óscar Luís Vaca Cevallos; Data Col- lection And/Or Processing: Miguel Ángel Blasco Carlos, Óscar Luís Vaca Cevallos; Analysis And/Or Interpretation: Miguel Ángel Blasco Carlos, Óscar Luís Vaca Cevallos, Miguel Ángel García Bereguiain; Literature Review: Miguel Ángel Blasco Carlos, Miguel Ángel Gar- cía Bereguiain; Writing The Article: Miguel Ángel Blasco Carlos; Crit- ical Review: Ángel García Bereguiain; References And Fundings: Óscar Luís Vaca Cevallos; Materials: Óscar Luís Vaca Cevallos.

Conflict of Interest: The authors declare that they have no conflict of interest. Financial Disclosure: There is no organization that funded our research.

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Address for Correspondence: Miguel Ángel Blasco Carlos, ESPOL Polytechnic University. Escuela Superior Politécnica del Litoral, ESPOL. CIBE y FCV. Campus Gustavo Galindo, Ecuador

E-mail: mblasco@espol.edu.ec Received: 16.05.2017 Accepted: 28.11.2017