Effect of Experimental Hypothyroidism on Glomerular Filtration Rate and Plasma Creatinine Concentration in Dogs

Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively. In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism. Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log(10)(fT4 post-treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r(2) = 0.81, P < 0.0001) and estimated GFR (0.69, P < 0.0001). The kidney is an important target of thyroid hormone action.

This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.

Changes in routine clinical chemical indicators of renal function in the hypothyroid state are not well characterized, and are infrequently discussed in standard internal medicine or subspeciality textbooks. We evaluated 24 consecutive patients with iatrogenic hypothyroidism induced prior to radioiodine scanning for monitoring of thyroid carcinoma. Serum creatinine and thyroid function tests were measured prior to, during, and subsequent to the period of induced hypothyroidism. Among 29 episodes with paired prior euthyroid and hypothyroid serum creatinine values, the hypothyroid value was greater in 26 (89.7%), and equal in 3 (10.3%), less in none; the mean hypothyroid value was significantly greater (103 vs 76 micromol/L [1.17 vs 0.87 mg/dL]) (P<.001). Among 36 episodes with paired hypothyroid and subsequent euthyroid serum creatinine values, the hypothyroid value was greater in 33 (91.7%), equal in 2 (5.6%), and less in 1 (2.8%); the mean hypothyroid value was again significantly greater (102 vs 75 pmol/L [1.15 vs 0.85 mg/dL]) (P<.001). There was no significant difference between prior and subsequent euthyroid serum creatinine values. Serum creatinine values above the stated normal range occurred in 6 of 36 hypothyroid episodes. There is a consistent and reversible elevation of serum creatinine values in the hypothyroid state. Frankly abnormal serum creatinine levels will occur in some cases.