European Journal of Cardiovascular Medicine

Electrolytes are crucial for maintaining the body's fluid equilibrium, facilitating neuronal transmission, and promoting muscular contractions [1]. Thyroid hormones, namely thyroxine, triiodothyronin, and thyroid stimulating hormone, play a pivotal role in the regulation of various physiological processes, including hemodynamics, thermodynamics, and metabolism. Moreover, it has been well-established that both thyroid and parathyroid diseases have a significant impact on the levels of calcium and sodium in the bloodstream [1]. In their investigation, Bharti et al. observed a notable reduction in calcium levels among individuals diagnosed with hypothyroidism [1].

This phenomenon can be attributed mostly to the impact of reduced levels of thyroxin (T4). The T4 hormone typically modulates calcium levels by facilitating the release of calcium ions from cells. In addition, they documented notably elevated phosphorus levels in individuals with hypothyroidism [1]. Finally, it was observed that hypothyroidism patients had considerably lower salt levels compared to their control group, although there were no significant differences in potassium levels across the various groups [1]. Their findings align with existing literature, with the exception of the lack of consensus about sodium and potassium levels across several studies, as well as the potential influence of TSH, T3, and T4 on these levels [2]. According to Baajafer et al., a mere 3.9% of their hypothyroid patients exhibited hyponatremia [3]. According to Sun et al., hyponatremia was not frequently observed in their cohort with severe TSH increases [4].

This assertion was further corroborated by Wolf et al., who documented that the concurrent presence of hyponatremia and hypothyroidism is likely a fortuitous occurrence and can be attributed to alternative factors [5]. Although chronic hypothyroidism has been associated with a decrease in antidiuretic hormone (ADH) levels, resulting in reduced sodium levels (hyponatremia), recent research has further substantiated these findings. It has been observed that factors other than hypothyroidism can contribute to the development of hyponatremia, which is typically observed in cases of severe hypothyroid disease and myxedema [6].Nagata et al. found that 1.3% of 71,817 patients with hyponatremia had overt hypothyroidism, and the severity of hyponatremia was strongly linked to the prevalence of hypothyroidism [7]. Calcium and phosphorous, as vital elements within the human body, are subject to regulation through a multitude of methods. Any alteration in the equilibrium of these minerals can result in detrimental consequences within the human body. Hypercalcemia can lead to several undesirable effects, including anorexia, disorientation, psychosis, and renal stones, among others.

 Hypocalcemia is characterized by symptoms such as muscle cramps, paresthesia, tetany, seizures,andothers [8].Thyroid hormones, in addition to vitamin D, calcitonin, and parathyroid hormones, are also involved in regulating calcium and phosphorous levels in our body [8,9]. The thyroid hormones, including FT3, FT4, and TSH, have significant implications for cellular development, thermogenic regulation, as well as mineral and metabolic functions inside the human body [10]. Hyperthyroidism has been identified as a contributing factor to the reduction in bone mineral density, the occurrence of osteoporotic fractures, as well as the presence of hypercalcemia and hyperphosphatemia. In addition, it is well-established that hypothyroidism can lead to the development of hypocalcemia and hypophosphatemia [11-14]. Moreover, hyperthyroidism has the potential to induce heightened bone turnover and impaired calcium mobilization, resulting in elevated levels of serum minerals.In the context of hypothyroidism, an inverse impact is observed [9,11]. Nevertheless,previous research has yielded inconsistent findings regarding the impact of calcium and phosphorous on thyroid diseases. Several investigations have demonstrated that thyroid diseases are associated with normal levels of calcium and phosphorous, while there have also been reports of abnormal amounts [15].

The objective of our research was to assess the blood calcium and phosphorous concentrations in individuals with hyperthyroidism and hypothyroidism, and to compare theselevels with those of healthy individuals in order to investigate the impact of thyroid hormones on serum calcium and phosphorous levels.

At Index Medical College and Hospital in Indore, a case-control study was undertaken to assess the levels of serum electrolytes, calcium, and phosphorus in individuals diagnosed with thyroid dysfunction. A total of 419 cases were evaluated, consisting of 100 healthy controls, 294 hypothyroid patients, and 25 hyperthyroid patients. The participants were divided into three distinct age cohorts: 21-30, 31-40, and 41-45, while the control group was matched based on age. The clinical examination encompasses the assessment of BMI (Kg/m2), age, and gender frequency. The laboratory analysis involves the measurement of thyroid hormones, specifically free T3, free T4, and TSH, using ELISA. The Easylyte plus (Na, K, Cl) electrolyte machine was used to assess serum electrolyte levels.

Selection Criteria: The present study has a cohort of 419 individuals between the age range of 20 to 60 years. The period of the study spans 3 years, and the subjects were divided into 3 distinct groups.
Group I consisted of 294 cases of primary hypothyroidism.
Group II consisted of 25 instances of primary hyperthyroidism.
Group III: Control group consisting of 100 participants.
This study focuses on the population of individuals who are receiving outpatient care at the Medicine Department.

Inclusion criteria:
The age range of individuals diagnosed with Hypothyroidism and Hyperthyroidism often spans from 20 to 60 years.
Exclusion criteria:

1. Pregnancy

1. Lactating mothers
2. Secondary thyroid dysfunction
3. Alcohol and smoking
4. History of Renal or Hepatic disease
5. History of various endocrine disorders

Ethical consideration: The current study was carried out after the approval of the Institutional Ethics Committee (IEC) to use human subjects.

Sample collection: A comprehensive medical history was obtained throughout the sample collection process. In accordance with aseptic protocols, a volume of 5 mL of fasting venous blood was collected from each participant. The samples underwent coagulation, followed by centrifugation for a duration of 10 minutes, resulting in the separation of serum. The serum sample underwent estimation for the subsequent biochemical tests and was subsequently stored in a refrigerated environment for future utilization.

Statistical analysis: The biochemical parameters mentioned above were compared between the patients and controls using a student t-test. The results were represented as the mean ± standard deviation. The statistical software SPSS Package Version 21 was utilized to compute Karl Pearson's correlation coefficient to establish correlations between the parameters across the cases. Significant p-values of 0.05 and 0.01 were deemed to be statistically significant and highly significant, respectively.

The study's statistical analysis revealed a statistically significant rise (p value < 0.001) in the serum calcium levels (11.14 ± 0.38) and phosphorous levels (4.48 ± 0.49) among patients with hyperthyroidism. The hyperthyroid group exhibited a considerable increase in serum potassium levels (4.58± 0.49). Nevertheless, the hyperthyroid group exhibited a notable reduction (p value 0.001) in serum sodium (133.11 ± 2.20) and chloride (100.73 ± 0.60) levels compared to the control group (Table 2). The findings of our study indicate a statistically significant reduction (p < 0.001) in the concentrations of serum calcium (7.66 ± 0.27) and phosphorous (2.83 ± 0.61) among individuals with hypothyroidism. Nevertheless, the hypothyroid group exhibited a notable reduction (p value 0.001) in serum sodium (132.23 ± 1.06), potassium (4.16 ± 0.21), and chloride (100.47 ± 0.76) levels compared to the control group (Table 2).

Table No – 1. Comparison of FT3, FT4 and TSH among the study and control group.

*Highly significant at the 0.01 level.

Table No – 2.Comparison of Electrolyte parameters among the study and control group.

*Highly significant at the 0.01 level.

Table No – 3. Correlation between TSH with different parameters among Hyperthyroid group.

Table No- 4. Correlation between FT3 with calcium and phosphorous among Hyperthyroid.

Table No- 5. Correlation between FT4 with calcium and phosphorous among Hyperthyroid.

Table No- 6. Correlation between TSH with different parameters among Hypothyroid group.

Table No- 7. Correlation between FT3 with calcium and phosphorous among Hypothyroid.

Table No- 8. Correlation between FT4 with calcium and phosphorous among Hypothyroid.

According to our study, there is a notable elevation in the levels of serum calcium and phosphorous when comparing individuals with hyperthyroidism to those without the condition. In the hyperthyroid group, a correlation analysis was conducted using Karl's Pearson Coefficient of correlation (r) to examine the relationship between TSH and various parameters. The results indicated a substantial negative association between TSH and both calcium (r = -0.45, p = 0.042) and phosphorous (r = -0.61, p > 0.05) (Table 3). There was a notable positive association observed between serum calcium and phosphorous levels and FT3 and FT4 levels in the hyperthyroid group, as indicated in Tables 4 and 5. Our investigation revealed a notable reduction in the levels of serum calcium and phosphorous in hypothyroid patients compared to healthy controls. In the hypothyroid group, a correlation analysis was conducted using Karl's Pearson Coefficient of correlation (r) to examine the relationship between TSH and various parameters. The results indicated a strong negative connection between TSH and both calcium (r = -0.554, p = 0.005) and phosphorous (r = -0.66, p > 0.05) (Table 6). There was a notable positive association observed between serum calcium and phosphorous levels and FT3 and FT4 levels in the hypothyroid group, as indicated in Tables 7 and 8. The levels of serum sodium, potassium, and chloride were associated with TSH in the hyperthyroid group, as shown in Table 3. In the hyperthyroid group, there was a negative correlation observed between serum salt and chloride levels and TSH, while a positive correlation was found between potassium levels and TSH. In the hypothyroid group (Table 6), there was a negative correlation between serum sodium and potassium levels and TSH, but serum chloride levels showed a positive correlation. Nevertheless, none of the observed associations exhibited statistical significance.

Hypothyroidism is a prominent endocrine disorder. It can result in several clinical conditions, such as congestive heart failure, electrolyte imbalance, and coma. According to Kargili et al. (2010), hyponatremia is the most prevalent electrolyte abnormality encountered in clinical settings. According to our study, there is a notable elevation in the levels of serum calcium and phosphorous when comparing individuals with hyperthyroidism to those without the condition. Our investigation, as shown in Table 2, revealed a notable reduction in serum salt and chloride levels, whereas potassium levels were substantially elevated in the hyperthyroid group compared to the control group. In Table 2, it was observed that individuals with hypothyroidism exhibited significantly reduced levels of serum calcium, phosphorous, serum sodium, potassium, and chloride in comparison to the control group (p<0.001). According to Saruta et al. (1980), it is possible that the suppression of Plasma Renin Movement (PRA) and Plasma Aldosterone (PA) in hypothyroidism is attributed to the dysfunction of juxtaglomerular cells and glomerulosa cells, respectively. It is also plausible that the suppression of PRA and PA in hypothyroidism patients is associated with increased sodium excretion and decreased potassium excretion.

A recent study conducted by Mariani and Berns (2012) examined the theoretical mechanisms that elucidate the relationship between thyroid function and serum salt levels. The primary mechanism for hypothyroid-induced hyponatremia in rats was found to be a reduced urinary dilution capacity resulting from the non-osmotic production of anti-diuretic hormone (ADH), along with an increase in urine salt loss (Schmitt et al., 2003). Promising investigations using extended follow-up periods in individuals diagnosed with recently diagnosed hypothyroidism and hyponatremia could provide valuable insights into the potential resolution of electrolyte imbalances following the initiation of hormone replacement therapy. Recently, there has been an observed association between hyponatremia and an elevated susceptibility to falls and fractures, hence highlighting the significance of this topic in relation to the patient's prognosis (Renneboog et al., 2006; Kinsella et al., 2010). Sodium and potassium play crucial roles as essential constituents of the protein Na-K ATPase, an enzyme located on the cellular membrane that facilitates the transportation of water and nutrients across the cell membrane. The movement of sodium-potassium pumps in many tissues is regulated by thyroid hormones. In hypothyroidism, the enzyme is impacted by low potassium levels and insufficient thyroid hormones, leading to the buildup of water within the cells and the development of edema.

According to Murgod and Soans (2012), this process is purportedly implicated in the observed weight gain among individuals with hypothyroidism. Hypothyroidism was found to have a negative correlation between serum sodium, potassium, and chloride levels and TSH. In the context of hyperthyroidism, there exists a negative association between serum sodium and chloride levels and TSH levels, while a positive correlation is shown between serum potassium levels and TSH levels. The study conducted by Morgood et al. demonstrated a notable inverse correlation between TSH, serum sodium, and potassium levels in individuals with hypothyroidism. The thyroid gland is responsible for the secretion of two essential hormones, namely T3 and T4. They have an impact on many digestion systems, including those involved in the breakdown of carbohydrates, lipids, and proteins. In addition, they regulate water and electrolyte balance. In recent times, there has been an increased focus on thyroid hormones due to their significant influence on mineral metabolism. 27 A comparison is made between the concentrations of serum calcium and phosphorous in these groups and those of healthy controls. According to our research, there is a notable elevation in the levels of serum calcium and phosphorous when comparing individuals with hyperthyroidism to those without the condition. The findings of our study align with the research conducted by Indrajit Nath et al. (16), Shivleela MB et al. (17), Abdelgayoum A. (18), Mosekilde et al. (19), and Manicort et al. (19).23

According to our study, there is a notable reduction in the levels of serum calcium and phosphorous observed in individuals with hypothyroidism compared to the control group. The research conducted by D. Sridevi et al. (20), Malamos et al. (21), and Gamage et al. have yielded comparable findings. [22] According to our study, there is a significant inverse correlation between Serum TSH and Serum Calcium (p-value 0.042) in hyperthyroidism. This indicates that as the severity of hyperthyroidism increases, the level of calcium in the bloodstream will also increase. There exists a significant inverse correlation between serum TSH and serum calcium levels (p-value <0.05) in individuals with hypothyroidism, indicating that as the severity of hypothyroidism escalates, there is a corresponding reduction in blood calcium concentration. The findings shown here are consistent with the studies conducted by Indrajit Nath et al. (16), Abdelgayoum A. (18), Mosekilde et al. (19), Malamos et al. (21), and Gamage et al. (22). The elevated serum calcium and phosphorous levels observed in individuals with hyperthyroidism can be attributed to the influence of thyroid hormones on osteoblasts, leading to the stimulation of osteoclastic bone resorption through nuclear receptors. This process ultimately results in an augmented bone turnover. The suppression of parathyroid hormone (PTH) and its direct impact on tissue phosphate metabolism and kidney phosphate levels would result in alterations in concentration. The underlying biochemical mechanism responsible for the impact of thyroid hormones on minerals such as blood calcium and phosphorous is intricate. Increased sensitivity of beta-adrenergic receptors to catecholamines is observed in individuals with hyperthyroidism. Thyroid hormones, particularly T3, enhance the responsiveness of IL-6 to bones, leading to an increase in osteoclastic differentiation through the upregulation of the nuclear factor κB ligand receptor. All of these factors result in elevated levels of serum calcium and phosphorus. In the context of hypothyroidism, an inverse impact will manifest. [16,24,25,26]. Hypothyroid individuals may experience heightened calcitonin synthesis alongside reduced intracellular thyroxine (T4) levels, resulting in augmented calcium excretion through the tubules and diminished extracellular calcium release. Consequently, this can lead to a decline in serum calcium concentration.[20]

Our study has demonstrated a reduction in serum sodium, potassium, and chloride levels among individuals with hypothyroidism in comparison to those with euthyroidism. In instances of hyperthyroidism, there was a reduction observed in serum sodium and chloride levels. Nevertheless, hyperthyroid individuals exhibited elevated levels of serum potassium. This implies that individuals with hypothyroidism and hyperthyroidism may experience abnormalities in electrolyte levels, necessitating regular monitoring of serum electrolyte levels and proper treatment to mitigate potential problems. The conditions of hypercalcemia and hypocalcemia are frequently overlooked in the context of India. They have the potential to result in a range of defects and impairments. Our investigation revealed that thyroid hormones have an impact on serum calcium and phosphorous levels. In instances when thyroid hormone imbalances are present, it is imperative to monitor changes in serum calcium and phosphorous levels as a preventive measure against potential problems.

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