Thyroid hormone deficiency impairs kidney function

Glomerular filtration rate fell by 18% in patients with suspended hormone replacement during radioiodine treatment, according to a study by Brazilian scientists published in Thyroid.

By Karina Toledo  |  Agência FAPESP – A study by Brazilian scientists published in the journal Thyroid has provided the first direct evidence that thyroid hormone deficiency impairs kidney function.

The researchers found that the rate of glomerular filtration, the first step in urine formation in the kidney, fell by 18% on average when hormone replacement therapy in patients subjected to total thyroidectomy due to cancer was temporarily suspended.

The study was performed with support from FAPESP as part of George Barberio Coura Filho’s PhD research, supervised by Marcelo Sapienza, a researcher affiliated with the University of São Paulo’s Radiology Institute (InRad-USP) and a professor at its medical school (FM-USP).

“Evidence in the scientific literature suggested that some patients with thyroid dysfunction had associated renal dysfunction, but there were few studies on the subject, and they assessed renal function indirectly,” said Coura Filho, who is also a director of the Brazilian Nuclear Medicine Society (SBMN).

The group therefore decided to investigate whether glomerular filtration rate, the usual parameter for assessment of kidney function, is determined by thyroid hormone levels.

The 28 patients involved in the study had no known renal disease or dysfunction. They had undergone surgical removal of their thyroids after being diagnosed with cancer and had been referred for complementary treatment with iodine-131, a radioactive substance, to reduce the risk of recurrence and metastasis.

“To increase the efficiency of treatment with radioiodine, it’s necessary to raise the level of thyroid-stimulating hormone, which is produced by the pituitary gland and facilitates cellular uptake of iodine,” Coura Filho explained.

There are two ways to achieve this goal, he added: administering a synthetic version of thyroid-stimulating hormone (TSH) or suspending thyroid hormone replacement therapy, which makes the pituitary produce TSH in an attempt to compensate for the deficit.

Before treatment with radioiodine was initiated, the 28 patients were divided into two groups. Half received synthetic TSH; in the other half, hormone replacement therapy was suspended, inducing a clinical state of hypothyroidism.

The researchers then assessed each group’s glomerular filtration rate using a nuclear medicine technique that entailed injection of chromium-51 ethylene diamine tetra-acetic acid (Cr-51-EDTA).

“Cr-51-EDTA is a radiopharmaceutical that’s widely used to assess glomerular filtration,” Coura Filho said. “It serves as a marker for this process because it’s filtered exclusively by glomeruli, without significant secretion or absorption in the kidney tubules, where the second step in making urine occurs. So, the higher the glomerular filtration rate, the faster the radioactive marker is excreted by the organism.”

Two and four hours after the radioisotope was injected, blood samples were taken from both groups of volunteers and placed in a radiation counter.

“The analysis showed that the glomerular filtration rate fell 18% on average compared with the initial level in the group whose hormone replacement had been suspended,” Coura Filho said. “In the group that received synthetic TSH, we observed a rise of 4% in the filtration rate, but this increase wasn’t statistically significant. Therefore, we can say that kidney function remained stable in this case.”

Waste retention

When the glomerular filtration rate falls, less urine is produced, such that toxins and undesirable metabolites are retained by the organism. One of the techniques most frequently used to determine whether this is happening is to measure the level of creatinine in the patient’s urine or blood.

Creatinine is a chemical waste product in the blood that passes through the kidneys to be filtered and eliminated in urine. The chemical waste is a by-product of normal muscle contractions. Creatinine is a breakdown product from creatine phosphate, a supplier of energy to muscles.

The researchers found that urinary excretion of creatinine fell by 22% in patients whose hormone replacement had been suspended. An increase in blood creatinine was also observed in these patients.

Sapienza believes the study clearly shows that even acute hypothyroidism leads to a significant reduction in glomerular filtration, which could have implications for the pharmacokinetics of other drugs and worsen the condition of patients with prior kidney disease.

“Hypothyroidism is probably associated with a reduction in renal function because it leads to alterations in the cardiocirculatory system, perhaps due to changes in renal water and electrolyte transport,” Sapienza said. “Although this association is well known in other situations, we still don’t know the degree to which this dysfunction occurs in acute hypothyroidism and with what kind of time lag, or how to quantify it in clinical practice. The study not only measured the impact of acute hypothyroidism on glomerular filtration in terms of plasma clearance, i.e., urinary excretion, of Cr-51-EDTA but also established parameters for clinically feasible monitoring based on the measurement of serum creatinine levels.”

For Coura Filho, the results reinforce the need for efficient thyroid hormone replacement. “Now that we know how thyroid hormones interact with kidney function, we can prevent patients with primary hypothyroidism, in whom the gland is present but not working properly, from suffering kidney damage in the future. We should take preventive measures,” he said.

The article “Effects of Thyroid Hormone Withdrawal and Recombinant Human Thyrotropin on Glomerular Filtration Rate During Radioiodine Therapy for Well-Differentiated Thyroid Cancer” (doi: 10.1089/thy.2015.0173) can be read at online.liebertpub.com/doi/10.1089/thy.2015.0173.