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ORIGINAL ARTICLE
Year : 2022  |  Volume : 20  |  Issue : 4  |  Page : 235-239

A study to evaluate the outcomes of hypothyroidism on serum potassium levels in an urban female population of Eastern India


1 Department of Physiology, Profulla Chandra Sen Government Medical College, Arambagh, West Bengal, India
2 Department of Physiology, Burdwan Medical College, Burdwan, West Bengal, India

Date of Submission27-May-2022
Date of Decision30-Jun-2022
Date of Acceptance20-Jul-2022
Date of Web Publication17-Oct-2022

Correspondence Address:
Dr. Arunima Chaudhuri
Krishnasayar South, Borehat, Burdwan - 713 102, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmi.cmi_62_22

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  Abstract 


Background: The association between thyroid dysfunction and electrolyte imbalance may result in significant morbidity. The present study was conducted to evaluate the effect of hypothyroidism on serum potassium levels in an urban female population of Eastern India. Materials and Methods: The present study was conducted in a peripheral Medical College in West Bengal for 12 months after taking Institutional Ethical Clearance and informed consent of the participants. One hundred and fifty hypothyroid females were included in the study group and one hundred participants were included as a control. The participants of both groups were age-matched. Serum thyroid-stimulating hormone (TSH) and free thyroxine 4 (FT4) levels were estimated by the enzyme-linked immunosorbent assay method and serum potassium was estimated by ion-selective electrode. Unpaired t-test and correlation coefficient were used for the analysis of data. Results: Hypokalemia was observed in 23 participants among the 150 hypothyroid females included in the study (15.33%). There was a significant difference in TSH (P < 0.00001), FT4 (P < 0.00001), and potassium levels (P = 0.000031) between the study and control groups. Serum potassium levels were strongly negatively correlated with TSH levels (r = −0.7356, P < 0.00001), the R2 value of 54.11%, and positively correlated with FT4 levels (r = 0.224, P = 0.005859). Conclusions: 15.33% of hypothyroid females included in the study had hypokalemia and serum potassium levels were significantly less in hypothyroid females as compared to euthyroid controls and serum potassium levels were negatively correlated with TSH levels. Serum electrolyte estimation may be of considerable importance in the management of hypothyroid individuals and needs to be considered and may help to prevent further possible complications.

Keywords: Hypokalemia, hypothyroidism, Indian urban female population


How to cite this article:
Koner S, Chaudhuri A. A study to evaluate the outcomes of hypothyroidism on serum potassium levels in an urban female population of Eastern India. Curr Med Issues 2022;20:235-9

How to cite this URL:
Koner S, Chaudhuri A. A study to evaluate the outcomes of hypothyroidism on serum potassium levels in an urban female population of Eastern India. Curr Med Issues [serial online] 2022 [cited 2022 Dec 5];20:235-9. Available from: https://www.cmijournal.org/text.asp?2022/20/4/235/358649




  Introduction Top


In India, about 42 million people suffer from thyroid problems and very common among the general population.[1],[2],[3] The prevalence of hypothyroidism is more common in the female population.[4],[5] Hypothyroidism results from primary gland failure or inadequate stimulation of the thyroid gland by the hypothalamus or pituitary gland.[5] Thyroid hormones affect the functioning of almost all organ systems and are of critical significance for normal and intellectual development.[1]

Thyroid hormones perform many metabolic functions including regulation of carbohydrates, protein, lipid, electrolyte, and mineral metabolisms.[3] Electrolytes play an important role in many body processes, consisting of controlling fluid levels, pH, blood clotting, nerve conduction, and contraction of the muscle.[2]

Hypokalemia occurs due to abnormal losses, insufficient intake, or transcellular shift and abnormal losses of potassium are most common. Often hypokalemia is asymptomatic but evaluation starts when warning signs or symptoms such as palpitations, weakness, or electrocardiography (ECG) changes are found.[6]

Potassium acts as an essential nutrient and is mostly found the as main cation in intracellular fluid.[7] Hypokalemia occurs when serum potassium levels are lower than normal. It is a common electrolyte disorder, with various causes found especially in hospitalized patients, and sometimes requires urgent medical attention.[8]

Potassium plays a major role in cell function, particularly in nerves and muscles, and also improves glucose intolerance, glucose control, and, insulin resistance for hypertensive individuals taking potassium wasting diuretics.[7] Intracellular K+ helps in acid-base regulation through the exchange for extracellular hydrogen ions (H+) and by controlling renal ammonium production. Na+-K+-ATPase' pump creates a K+ gradient across the cell membrane (K+in > K+ out), which is partially responsible for maintaining the potential difference across the membrane.[8]

Na+-K+ ATPase pump is the membrane-spanning protein complex that causes the exit of Na+ and absorption of K+ by most animal cells. It includes a catalytic alpha subunit (100,000 Da) and a glycosylated beta subunit (50–60 000 Da).[9] The iodine needed for thyroid hormone synthesis is accumulated within the thyroid gland by the actions of the Na+-K+ ATPase, and the Sodium-Iodide transporter present in the follicular epithelium of the thyroid gland.[9]

Na+-K+ ATPase enzyme is present on the cell membrane and the activity of sodium-potassium pumps is regulated by thyroid hormones in most tissues.[2],[10],[11] Because of the deficiency of thyroid hormones, this enzyme is affected. Hypothyroidism causes a remarkable change in the metabolism of water and electrolytes.[10],[11],[12] In hypothyroidism, weight gain may occur as a result of the accumulation of water inside the cell leading to edema due to a low level of potassium.[13]

The effects of hormonal influence on the Na+-K+-ATPase pump are less studied in the thyroid gland. Furthermore, the outcome of hypothyroidism on electrolytes has not been well established and the mechanisms behind it are also not well understood. Hence, the present study was conducted to evaluate the outcome of hypothyroidism on serum potassium levels in an urban female population of Eastern India. We also assessed the correlation between thyroid-stimulating hormone (TSH) and serum potassium levels in hypothyroid individuals in our study.


  Materials and Methods Top


This cross-sectional study was conducted in Burdwan Medical College and Hospital on 150 newly diagnosed hypothyroid female subjects during a time period of 12 months after taking Institutional Ethical Clearance (Memo No.BMC/PG/4423, dated: December 14, 2015) and written informed consent of the subjects. 100 controls were taken for the study. The subjects of the two groups were dietary habits matched. The sample size was calculated using an online sample size calculator available at calculator. Net, the confidence level was 95%, and the margin of error was 5%. Around 200 female hypothyroid patients attend the medicine outpatient department (OPD). The sample size calculated was 132. Considering dropouts, 150 patients were included in the study. Only 100 subjects were willing to participate as a control at the time the study was conducted, so the study and control arm were not the same.

Inclusion criteria

One hundred and fifty newly diagnosed (diagnosis done within 1 week before inclusion) hypothyroid female individuals of reproductive age group attending the Medicine OPD, Burdwan Medical College, and Hospital were included in the study, and 100 control subjects were enrolled.

Exclusion criteria

Subjects having vomiting or diarrhea, receiving medications causing hypokalemia like furosemide and steroids, undergoing dialysis or having a history of renal disease, and having hepatic disorders were excluded.

Methods

Before the conduction of the study approval from the Institutional Ethics Committee was obtained and informed consent was taken from the participants. Patients were selected from medicine OPD. Random numbers were generated using an online randomizer for the selection of participants. History in detail was taken from each subject according to case record format and a general physical examination was done. Patients included in the study were not taking treatment – thyroxine or were defaulters or their thyroid function was well controlled.

After overnight fasting, 5 ml of venous blood was collected in a plain vial by venipuncture under strict aseptic conditions and was allowed to clot at the room temperature. Then, the blood samples were sent to the biochemical laboratory and centrifuged at 3000 rpm for 15 min for the separation of serum.

Serum was assayed for the estimation of TSH and free thyroxine 4 (FT4 by Enzyme-Linked Immunosorbent Assay (ELISA) method using Accubind ELISA kits manufactured by Monobind Inc. The USA and microplate ELISA reader. Controls were tested at levels in the hypothyroid, euthyroid, and hyperthyroid range to monitor assay performance. These controls were treated as unknowns and values were determined in each test procedure performed. Quality control was maintained to track the performance of the reagents supplied.

Serum potassium was estimated by ion-selective electrode using Medica Easylyte auto analyzer. Controls were used on a daily basis to the accuracy and precision of the analyzer. EasyLyte was calibrated, and then, the quality control results obtained within the specified range or not were observed. Controls were run at levels in the low, normal, and high range for monitoring assay performance. Approximately 95% of means from the analyzer, operating within specification, were expected to fall within the ranges

Hypothyroidism was defined as an elevated TSH (>6.16 μ IU/ml) with a decreased (<0.8 ng/dl) or normal serum FT4 level (range: 0.8–2.0 ng/dl) as per the kit values.

Hypokalemia was considered as decreased level of serum potassium concentration below 3.6 mEq/l (normal value: 3.6–4.2 mEq/L as per reference value).

All the subjects were examined in the postmenstrual phase as there is normal retention of fluid in the premenstrual phase.

Statistical data analysis

The computer software “Statistical Package for the Social Sciences (SPSS) version 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.)” was used to analyze the data. The difference between the groups was considered significant and highly significant if the analyzed probability values (P value) were P < 0.05* and P < 0.01**, respectively. An unpaired t-test was used to compare the two groups and the correlation coefficient was calculated to study the correlation between serum potassium and TSH, and FT4 levels.


  Results Top


One hundred and fifty newly diagnosed hypothyroid female subjects and 100 controls were enrolled in our study. All participants of the study were on a nonvegetarian diet and they belonged to a lower socioeconomic group and belonged to the same district as the institution. There was no significant difference in age between the two groups (Age in years: 30.22 ± 4.67 vs. 29.75 ± 4.83; P = 0.446). The participants were not suffering from any other comorbid conditions except anemia.

Twenty-three participants were having hypokalemia out of 150. Hypokalemia was found in 15.33% of hypothyroid subjects. A significant difference was observed between control and hypothyroid subjects for mean TSH (P < 0.00001), mean FT4 (P < 0.00001) and mean serum potassium (P = 0.000031). No significant difference was observed in mean age between control and hypothyroid subjects [Table 1] and [Figure 1].
Table 1: Age, thyroid stimulating hormone, free thyroxine 4, and serum potassium values of control and hypothyroid subjects

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Figure 1: Difference in age, TSH, FT4, and serum potassium values between control and hypothyroid subjects. TSH: Thyroid-stimulating hormone, FT4: Free thyroxine 4.

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Serum potassium level was strongly negatively correlated with serum TSH with a predictive value of 54.11% (r = −0.7356, P < 0.00001) [Table 2] and [Figure 2], and serum potassium were positively correlated with Sr. FT4 (r = 0.224, P = 0.005859) [Figure 3].
Table 2: Correlation table

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Figure 2: Serum potassium level was negatively correlated with Sr. TSH (r = −0.7356, P < 0.00001). TSH: Thyroid-stimulating hormone.

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Figure 3: Serum potassium was positively correlated with Sr. FT4 (r = 0.224, P = 0.005859). FT4: Free thyroxine 4.

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  Discussion Top


Worldwide thyroid disorders are common.[1],[14],[15] A significant burden of thyroid disorders is also found in India.[14] Renal hemodynamics, renin-angiotensin-aldosterone system, glomerular filtration, and renal electrolyte handling are influenced by thyroid hormone.[16],[17],[18] Hypothyroidism results in clinical conditions like electrolyte disturbances and congestive heart failure and then results in a coma if untreated.[3],[11]

A decrease in serum T3 and T4 concentration causes hypersecretion of pituitary TSH and an increase in serum TSH levels and these laboratory findings help particularly in the early detection of thyroid failure.[4]

Kavitha et al. 2014 in their study observed significantly reduced serum potassium levels (P < 0.001) in subclinical and overt hypothyroidism compared to euthyroid and a negative correlation between TSH and serum potassium.[10] A study by Kaur et al. showed low potassium levels in hypothyroid patients.[4] Babiker et al. 2018 reported a significant effect of hypothyroidism on serum potassium level.[19]

The Sodium and potassium are the principal components of the Na+-K+ ATPase and the activity of sodium-potassium pumps is regulated by thyroid hormones in most the tissues.[11] Na+-K+ ATPase enzyme is deficient in hypothyroidism because of suppression of plasma renin activity and plasma aldosterone as a result of dysfunction of juxtaglomerular cells and glomerulosa cells and results in altered excretion of sodium and potassium.[18]

A study in 1999 examined the enzymatic activity of Na+-K+ ATPase and also the adequacy of the enzyme subunits in glands from hypothyroid and hyperthyroid rats. The results noticed that the Na+-K+ ATPase of the thyroid gland is stimulated dramatically by hypothyroidism, in direct contrast to the feedback in nonthyroidal tissues.[9]

Hypokalemia may cause metabolic acidosis, leg cramps, weakness, ascending paralysis, constipation, and intestinal paralysis. It may also lead to ECG changes, cardiac arrhythmias, and heart failure.[8]

A study in 2019 observed no significant relationship between serum potassium and thyroid hormone.[20] Krishna et al. 2018 in their study reported reduced serum potassium levels in hypothyroid people.[11] Another study in 2012 noticed decreased serum potassium levels in hypothyroid patients when compared to controls and a significant negative correlation (P = −0.002) was found between serum potassium levels and serum TSH values.[3]

A study by Arambewela et al. showed hypokalemic periodic paralysis associated with hypothyroidism and neuromyotonia.[21] Another case report in 2012 reported hypokalemic periodic paralysis associated with hypothyroidism.[22] Dambal et al. noticed in their study a statistically significant decrease in serum potassium in cases as compared to controls (P < 0.0001) and a negative correlation between TSH and serum potassium level among cases.[17]

As per current experimental studies, hypokalemia-induced arrhythmias are initiated by the decreased action of the Na+/K+-ATPase (NKA) leading to Ca2+ overload, Ca2+/Calmodulin-dependent kinase II activation, and productions of afterdepolarizations.[23] Two principal side-effects of hypokalemia influencing the cardiovascular system are hypokalemia-related hypertension and hypokalemia-induced ventricular arrhythmias contributing to increased morbidity and mortality. Hypokalemia causes intravascular volume expansion as a consequence of renal NaC1 retention or salt retention resulting in hypertension and can also potentiate the hypertensive effects of different neurohumoral agents.[24]

Hypokalemia in hypothyroidism was also found in many other studies.[12],[25],[26],[27],[28],[29]

Spontaneous hypokalemia in healthy adults without receiving any medications should suggest the possibility of the underlying disease and indicates to search for an etiology.[24]

In the present study, a significant difference was observed between control and hypothyroid subjects for mean TSH (P < 0.00001), mean FT4 (P < 0.00001), and mean serum potassium (P = 0.000031). No significant difference was observed in mean age between control and hypothyroid subjects. We noticed 15.33% hypokalemia in hypothyroid subjects (23/150). Our study also demonstrated that serum potassium was significantly lower than the reference range in hypothyroid patients as compared to controls. Serum potassium level showed a negative correlation with TSH (R= −0.7356, P < 0.00001) and a positive correlation with Sr. FT4 (R = 0.224, P = 0.005859).

Our study findings are contradictory to Abedelmula et al., showing that significant increase in serum potassium levels in the hypothyroid group compared to controls.[30]

Limitations

This was a cross-sectional study and blood parameters were only assessed once in a single center. No long-term follow-up was done. This does a limitation of the present study. It was incidental one episode of hypokalemia and not serial hypokalemia without any renal disease. There were no subgroups in the study as all participants were newly diagnosed and not on treatment for hypothyroidism.


  Conclusions Top


In our study, we observed that the serum potassium level was decreased in hypothyroid females compared to euthyroid controls and strongly negatively correlated with serum TSH with a predictive value of 54.11%. Hence, the serum potassium should be regularly screened in hypothyroid patients to prevent further possible complications and it will be of great value for the patients.

Ethical statement

All authors of this manuscript declare that this scientific study is following standard reporting guidelines set forth by the EQUATOR Network. The authors ratify that this study required Institutional Review Board / Ethics Committee review, and hence prior approval was obtained from IRB Memo No. BMC/PG/4423; Dated: 14/12/2015. We also declare that we did not plagiarize the contents of this manuscript and have performed a Plagiarism Check with free software available online at small tools.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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29.
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    Figures

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    Tables

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