Impact of thyroid dysfunction on electrolyte balance and vitamin metabolism

Authors

Abstract

Aim: Thyroid dysfunction is known to contribute to electrolyte imbalances and vitamin deficiencies. The objective of this study was to examine the effects of thyroid disorders on serum electrolytes, as well as vitamin D and B12 levels, while also exploring their relationship with thyroid-stimulating hormone (TSH). Materials and Methods: Biochemical data of 150 participants with clinically established thyroid dysfunction (75 hyper and 75 hypo) were collected from the electronic records of the hospital. Vitamins B12 and D were analyzed for correlation with serum TSH levels.
Results: Electrolyte analysis revealed significant differences between hyperthyroid and hypothyroid groups (p < 0.001). Sodium levels were lower in hypothyroid patients (110.68 ± 8.24 mmol/L) and elevated in hyperthyroid patients (169.81 ± 13.67 mmol/L) compared to the normal range (132-145 mmol/L). A similar trend was observed for potassium and calcium, with lower levels in hypothyroid patients but normal levels in hyperthyroid patients. Conversely, chloride and phosphate levels were elevated in hypothyroid patients but decreased in hyperthyroid patients (p < 0.001). Vitamin D levels were low in both groups without a significant difference (p = 0.248), while vitamin B12 levels were significantly lower in hypothyroid and higher in hyperthyroid patients (p < .0.001). In hypothyroid patients, TSH showed weak, non-significant negative correlations with vitamin B12 (r = -0.101, p = 0.388) and vitamin D (r =-0.141, p = 0.228). Discussion: Thyroid dysfunction impacts electrolyte balance and vitamin metabolism. Patients with hypothyroidism should be routinely screened for vitamin D and B12 deficiencies to enable early treatment and prevent complications.

Keywords

Introduction

Thyroid hormones are required for the proper development, differentiation, metabolic homeostasis, and physiological functioning of nearly all tissues [1], and abnormalities in thyroid function represent some of the most common endocrine disorders. Thyroid disorders disproportionately affect women, particularly during the reproductive years [2]. Their prevalence varies by population, with hypothyroidism being the most frequently diagnosed disorder, affecting 2–5% of the global population [2, 3]. Hyperthyroidism, on the other hand, is less common, with a prevalence of 0.5 to 2% in women [1, 4].
Thyroid hormone is the primary regulator of physiological processes, and abnormalities in thyroid function are thought to be the root cause of electrolyte imbalances. Hospitalized individuals frequently experience electrolyte imbalances, with dysnatremias being the most prevalent. Recent studies have highlighted the association between electrolyte imbalances, particularly hyponatremia and hypernatremia, and increased mortality in affected patients [5]. However, it has also been demonstrated that deficiencies in magnesium, potassium, and phosphate might potentially indicate a higher risk of death [8].
Thyroid dysfunction is usually linked to calcium and phosphorus imbalances and is considered to be a major cause of secondary osteoporosis. Vitamin D insufficiency is a global health issue impacting more than a billion people worldwide [9]. Several autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), and type 1 diabetes (T1DM), have been linked to vitamin D deficiency, and supplementation with vitamin D was found to be effective in preventing the onset and/or progression of these autoimmune diseases [10]. Moreover, it was found that individuals suffering from Hashimoto’s thyroiditis had reduced vitamin D levels [11]. Vitamin D exerts its effects by binding to the vitamin D receptor (VDR) and thereby activating the corresponding genes [12]. As a result, low vitamin D levels are likely to worsen the systemic abnormalities associated with hypothyroidism. As a water- soluble vitamin, vitamin B12 is vital for protein synthesis, cellular replication, and the maintenance of normal growth. Vitamin B12 insufficiency has been found in people with autoimmune thyroid disease (AITD). Autoimmune thyroid disease refers to a group of disorders in which the immune system produces antibodies against the thyroid gland. The relationship between AITD and B-12 insufficiency might be linked to the presence of atrophic gastritis and/or pernicious anemia, both of which contribute to decreased absorption of B12 [13]. While iodine deficiency is the major cause of hypothyroidism around the world, AITD is the leading cause in the United States, where iodine fortification is widely used. In the absence of AITD, the relationship between hypothyroidism and B-12 insufficiency has not been well examined and may differ depending on dietary practices among various population groups [14]. Some earlier studies have investigated the influence of vitamin D and vitamin B12 insufficiency on thyroid disorders, but there is no agreement on the appropriate role of vitamin D and vitamin B12 deficiency in hypothyroid individuals or their relationship with hypothyroidism.
Therefore, this study was designed to evaluate the influence of thyroid dysfunction on serum electrolytes, vitamins D and B12, and to explore their association with thyroid-stimulating hormone (TSH).

Materials and Methods

Study Participants
A cross-sectional study was undertaken at a tertiary care hospital in New Delhi NCR (Noida), India, spanning a period of six months from June to November 2024. Clinical data were retrospectively extracted from hospital electronic medical records for 150 individuals diagnosed with thyroid dysfunction, comprising 75 cases of hyperthyroidism and 75 cases of hypothyroidism. All participants were treatment-naive at the time of data collection. The participants were divided into two groups: hypothyroidism and hyperthyroidism, based on their thyroid profile and symptoms.
Records of patients diagnosed with pregnancy, liver or kidney diseases, polycystic ovarian syndrome, chronic illnesses, or coronary heart disease were excluded from the analysis.
Informed consent: As the study involved a retrospective analysis of existing medical records, the requirement for informed consent was waived. The confidentiality and privacy of all collected data were rigorously protected.
Laboratory Measurements
Thyroid abnormalities were diagnosed and classified according to the guidelines established by the National Academy of Clinical Biochemistry (NACB) for the laboratory diagnosis and monitoring of thyroid disorders [15]. Hypothyroidism was diagnosed when TSH levels exceeded 4.2 µIU/mL and free thyroxine (FT4) levels were below 12 pmol/L. Conversely, hyperthyroidism was diagnosed when TSH levels were less than 0.27 µIU/mL and FT4 levels exceeded 22 pmol/L.
Thyroid hormones (free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH)) were measured by immunoassay methods using ELISA kits. The electrolytes (calcium, magnesium, phosphorus, sodium, potassium, and chloride) and vitamins D and B12 were analyzed on a Beckman Coulter DXC autoanalyzer using commercially available kits. The reference ranges for thyroid hormones and electrolytes (calcium, magnesium, phosphorus, sodium, potassium, and chloride), as determined by the assay kits used, are listed in Tables 1 and 2.
Statistical Analysis
Data were entered and analyzed using PSPP statistical software. Results are reported as mean ± standard deviation (SD). Pearson’s correlation coefficient (r) was used to evaluate associations between variables, with a p-value <0.05 considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of the Tertiary Care Hospital, Noida, India (Date: 2024-05-15, No: 16/30/D).

Results

The current study assessed thyroid hormone levels, serum electrolytes, and vitamin concentrations in patients with hypothyroidism and hyperthyroidism. A total of 150 participants with clinically diagnosed thyroid dysfunction (75 hypothyroid and 75 hyperthyroid) were included in the study. The mean age of hypothyroid patients was 43.99±13.29 years, with an age range of 18-74 years, and hyperthyroid patients was 46.03±11.79 years, with an age range of 19-74 years.
Thyroid function analysis (Table 1) revealed a significant difference in TSH levels (p<0.001), with hypothyroid patients exhibiting elevated TSH (10.40±2.23 µIU/L) and hyperthyroid patients showing suppressed levels (0.16±0.04 µIU/L). Similarly, FT3 and FT4 levels were significantly reduced in hypothyroid patients (2.52 ± 0.78 pmol/L and 10.06±0.89 pmol/L, respectively) and increased in hyperthyroid patients (9.96±1.19 pmol/L and 28.19±2.20 pmol/L, respectively) (p<0.001).
Electrolyte analysis (Table 1) demonstrated a significant difference in sodium levels between the two groups (p<0.001). Sodium was lower in hypothyroid patients (110.68±8.24 mmol/L) and markedly elevated in hyperthyroid patients (169.81±13.67 mmol/L) compared to the normal reference range (132-145 mmol/L). A similar trend was observed for potassium and calcium levels, with hypothyroid patients presenting lower concentrations (2.28±0.34 mmol/L and 1.39±0.14 mmol/L, respectively) relative to their reference ranges (3.5- 5.1 mmol/L and 2.12-2.52 mmol/L, respectively). However, in hyperthyroid patients, potassium (4.96±0.37 mmol/L) and calcium (2.45±0.19 mmol/L) levels remained within the normal range. Conversely, chloride and phosphate levels were elevated in hypothyroid patients (111.87±3.97 mmol/L and 1.88±0.23 mmol/L, respectively) but decreased in hyperthyroid patients (93.80±8.23 mmol/L and 0.65±0.11 mmol/L, respectively), with a significant difference between the groups (p < 0.001). The levels of serum magnesium were found to be higher than the reference range in both hypothyroid and hyperthyroid patients. The level of vitamin D was found to be low in both hypo and hyperthyroid groups, with no statistical difference (p=0.248) between these groups (Table 2). A significant difference (p<0.001) was observed in the levels of vitamin B12 between the two groups, with a reduced level in hypothyroid patients and an elevated level in hyperthyroid patients (Table 2).
Correlation analysis in hypothyroid patients demonstrated weak negative associations between TSH and both vitamin B12 (r = -0.101, p = 0.388) and vitamin D (r = -0.141, p = 0.228), neither of which was statistically significant (Figures 1 and 2).

Discussion

The study investigated the effect of thyroid dysfunction on serum electrolytes and vitamin concentrations among hypothyroid and hyperthyroid patients. The findings revealed significant alterations in thyroid hormone levels, consistent with expected physiological patterns. Hypothyroid patients exhibited markedly elevated TSH levels, whereas hyperthyroid patients demonstrated significantly suppressed TSH levels. Similarly, FT3 and FT4 concentrations were markedly reduced in hypothyroid patients, whereas hyperthyroid patients demonstrated elevated levels of these hormones. These findings align with the pathophysiology of thyroid disorders, where hypothyroidism is characterized by reduced thyroid hormone production and compensatory TSH elevation, while hyperthyroidism leads to excessive hormone secretion and TSH suppression. Thyroid hormones are pivotal in maintaining systemic hemodynamics, thermoregulation, and metabolism. As a result, they significantly influence renal hemodynamics, glomerular filtration, and electrolyte homeostasis [16]. Alterations in electrolyte balance were noted in this study, underscoring the widespread physiological impact of thyroid dysfunction. In cases of hypothyroidism, serum sodium and potassium concentrations were notably reduced, whereas serum chloride levels were elevated relative to the reference range. Conversely, in hyperthyroid patients, serum sodium levels were elevated while chloride levels were decreased, demonstrating a statistically significant difference compared to the hypothyroid group. These findings suggest that thyroid hormones are key modulators of sodium homeostasis, potentially through their effects on renal function and water balance. Sodium and potassium are essential components of Na⁺/K⁺-ATPase, an integral membrane enzyme responsible for regulating ion transport and maintaining cellular osmotic balance. Thyroid hormones modulate the activity of Na⁺/K⁺-ATPase across various tissues. In hypothyroidism, reduced potassium levels, coupled with thyroid hormone deficiency, impair the function of this enzyme, leading to intracellular water retention and subsequent edema. This mechanism is proposed to contribute to the weight gain commonly observed in hypothyroid patients [17]. Serum magnesium levels were found to be elevated beyond the reference range in both hypothyroid and hyperthyroid patients. This finding aligns with the results of Kaur et al. and Murgod et al., [17] who reported increased magnesium levels in individuals with hypothyroidism. Additionally, our study revealed a statistically significant elevation in serum phosphorus levels among hypothyroid patients (p < 0.01), whereas phosphorus levels were significantly reduced in hyperthyroid patients (p < 0.001). These observations corroborate the results reported by Suneel et al [18]. Which demonstrated a significant increase in mean phosphate levels in hypothyroid patients compared to controls. The observed changes in phosphate levels can be attributed to the regulatory role of calcitonin in tubular phosphate reabsorption in the kidneys. The elevation in phosphate levels in hypothyroid patients is likely a compensatory response involving calcitonin and parathyroid hormone (PTH), which modulate phosphate homeostasis by promoting its tubular excretion through inhibition of renal reabsorption [18]. Our study observed a decrease in serum calcium levels in the hypothyroid group, whereas calcium levels remained within the normal range in the hyperthyroid group, with a statistically significant difference between the two groups (p < 0.05). These alterations in calcium homeostasis may be attributed to thyroid hormone-mediated regulation of parathyroid hormone (PTH) and bone metabolism. Shivallela et al. reported a significant reduction in serum calcium levels in the subclinical hypothyroidism (SCH) group compared to controls, primarily due to decreased levels of PTH and calcitonin in hypothyroidism [19]. Similarly, Murgod et al. noted that thyroxine plays a critical role in calcium regulation by facilitating calcium release from cells. A decrease in thyroxine levels leads to reduced intracellular calcium mobilization due to diminished T4 entry into cells [17]. Furthermore, an animal study by Kumar and Prasad demonstrated that elevated TSH levels in rats were associated with increased renal calcium excretion, suggesting a potential mechanism for calcium depletion in hypothyroidism [20].
Vitamin analysis revealed a significant difference in the levels of vitamin B12 between hypothyroid and hyperthyroid groups, suggesting that thyroid dysfunction influences vitamin B12 metabolism, likely through alterations in gastric absorption and intrinsic factor secretion. In our study, vitamin B12 levels were below the normal reference range in hypothyroid patients, whereas they were elevated in the hyperthyroid group. Additionally, a weak negative association was identified between TSH and vitamin B12 levels in hypothyroid patients. Deficiency of vitamin B12 is a frequent finding among patients with autoimmune thyroid disease, possibly due to impaired absorption associated with atrophic gastritis and/or pernicious anemia, both of which are commonly linked to autoimmune thyroid disorders [13]. Atrophic gastritis has been documented in 35–40% of autoimmune thyroid cases [21], and studies indicate that one-third of patients with primary hypothyroidism have gastric parietal cell antibodies, while 12% present with pernicious anemia. Additionally, intrinsic factor antibodies have been detected in these patients, further impairing vitamin B12 absorption [22]. Regional variations exist in the prevalence of vitamin B12 deficiency among hypothyroid patients, with rates reported at 40.5% in Pakistan, 18.6% in Turkey, and 10% in India [23]. These differences may be attributed to variations in dietary habits and overall nutritional status. Vitamin B12 deficiency is known to elevate homocysteine levels [22], with hyperhomocysteinemia being linked to a higher risk of atherosclerosis. A growing body of evidence has linked hypothyroidism with elevated homocysteine concentrations. Consequently, an undiagnosed deficiency of vitamin B12 in hypothyroid individuals may contribute to increased cardiovascular risk through hyperhomocysteinemia.
This study found no statistically significant difference in vitamin D levels between hypothyroid and hyperthyroid patients. Low vitamin D levels were observed in both groups. Additionally, a weak negative correlation between TSH and vitamin D levels was observed in the hypothyroid group. Several observational studies have reported reduced serum vitamin D levels in individuals with both hypothyroidism and hyperthyroidism. However, it is still uncertain whether vitamin D deficiency serves as a causative factor, a consequence, or a coincidental association in the pathogenesis of these thyroid disorders. One hypothesis proposes that vitamin D insufficiency may contribute to immune system dysfunction, potentially facilitating the progression of thyroid disease. Conversely, individuals with thyroid disorders may experience altered health conditions or lifestyle factors that predispose them to vitamin D deficiency. The primary function of vitamin D is to regulate calcium and phosphorus homeostasis, thereby maintaining bone metabolism. However, emerging research suggests that vitamin D is implicated in the pathogenesis of various conditions, including autoimmune diseases, cardiovascular diseases, cancer, inflammatory bowel disease, diabetes, and rheumatologic disorders [24]. Furthermore, vitamin D is believed to play a role in the regulation of the immune system, as its receptors have been identified on immune cells. Studies have suggested an association between vitamin D deficiency and autoimmune thyroid diseases, such as Hashimoto’s thyroiditis (HT) and Graves’ disease. Additionally, impaired vitamin D signaling has been implicated in thyroid cancers [25].

Limitations

The study has a few limitations. One limitation of this study was its finite duration, which restricted the number of subjects included. Additionally, the study’s focus on patients from a single tertiary healthcare center limits the generalizability of the findings to the broader population.

Conclusion

The results underscore the significant impact of thyroid dysfunction on hormone regulation, electrolyte balance, and vitamin metabolism. Alterations in sodium, chloride, calcium, phosphate, and magnesium levels highlight the role of thyroid hormones in maintaining electrolyte homeostasis through renal and metabolic pathways. Additionally, changes in vitamin D and B12 levels suggest broader systemic effects, potentially contributing to fatigue and neurological symptoms. Given these findings, routine screening must be performed on hypothyroid patients for vitamin D and B12 deficiencies at diagnosis and follow-ups. Early detection and supplementation can help maintain optimal levels, prevent complications, and improve overall health. Additional studies are required to explore the underlying mechanisms and clinical consequences of these imbalances.

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