Relationship Between Hyponatremia and Elevated TSH Levels
There is a relationship between hyponatremia and elevated TSH levels, but it is more likely coincidental rather than causal in most cases, as both conditions are common independently and almost all cases of hyponatremia in hypothyroid patients have alternative explanations.
Physiological Connection Between Thyroid Function and Sodium Levels
Patients with primary adrenal insufficiency (PAI) can have TSH levels typically in the range of 4-10 IU/L due to the lack of inhibitory effect of cortisol on TSH production 1.
Hyponatremia is present in 90% of newly presenting cases of primary adrenal insufficiency, but this is primarily due to loss of sodium in urine and increases in plasma vasopressin and angiotensin II, which impair free water clearance 1.
In hypothyroidism, there is a proposed mechanism for hyponatremia involving decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output 2.
Evidence on the Association
Recent research suggests that hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema 2.
A 2017 retrospective analysis of 8,053 hypothyroid patients found that hyponatremia was present in only 5.56% of patients, and 98.88% of these cases had potential alternative causes for hyponatremia (medication side effects, concomitant diseases, or other endocrine disorders) 3.
No case of clinically relevant hyponatremia (Na+ < 130 mmol/L) could be attributed solely to hypothyroidism in this large study 3.
There was only a very weak statistical correlation between thyroid function and serum sodium levels (Na+/TSH: R = 0.022, p = 0.046; Na+/free thyroxine: R = -0.047, p < 0.001) 3.
Findings in Specific Patient Populations
In a study of thyroid-ablated patients with differentiated thyroid cancer, only 3.9% had sodium levels below 135 mEq/L when hypothyroid, and no patient had a sodium level less than 130 mEq/L 4.
When comparing euthyroid to hypothyroid states in the same patients, mean sodium levels changed by only -1.18 mEq/L (p=0.003), which is clinically insignificant 4.
A case series of 10 patients with extreme TSH elevations (>100 μU/mL) found that none had serum sodium levels below normal (<135 mmol/L), even in the presence of reduced glomerular filtration rate 5.
Clinical Implications
When evaluating patients with hyponatremia, thyroid function testing should be included as part of the workup, as hypothyroidism is one of the possible causes to consider 2.
However, clinicians should thoroughly investigate other more common causes of hyponatremia even when hypothyroidism is present, as the relationship appears to be coincidental rather than causal in most cases 3.
Treatment of hypothyroidism alone may not correct hyponatremia if other causes are present 2.
Treatment Considerations
For patients with both conditions, treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia 2.
Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines, regardless of thyroid status 2.
In rare cases where severe hypothyroidism is the primary cause of hyponatremia, thyroid hormone replacement can lead to significant improvement in sodium levels, as reported in a case study of a 70-year-old woman with Hashimoto's thyroiditis 6.
Conclusion
The evidence suggests that while there is a physiological basis for a relationship between hypothyroidism and hyponatremia, clinically significant hyponatremia solely attributable to hypothyroidism is rare. When both conditions coexist, other causes of hyponatremia should be thoroughly investigated, as they are likely to be present in the vast majority of cases.