Effects of myxedema on the renal diluting and concentrating mechanism

Abstract

The effect of myxedema on renal solute and water transport was evaluated in man by studying the diluting and concentrating mechanism in subjects with myxedema, prior to any treatment and in the course of therapy. While myxedematous, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were reduced. Defects in maximum urine flow rate (V) under hydrated conditions, rate of free water formed (CH 2O), maximum urine osmolality (Umax) and rate of free water of reabsorption (T c H 2O) were observed. The difference in minimal urine osmolalities (Umin) of 5 mOsm could not explain the reductions in V, which persisted despite normal GFRs in the intermediate studies, suggesting enhanced reabsorption of sodium by the proximal tubule, possibly due to the diminished blood volume in myxedema. Basal hydropenic studies showing similar minute excretion of sodium despite a lower GFR suggest a relative natriuresis secondary to a defect in distal nephron sodium reabsorption. A myxedematous subject who presented with a hypotonic plasma and hypertonic urine had a prompt and sustained water diuresis in response to a water load and a U:P osmolar gradient of 0.09. In contrast, a subject with carcinoma of the lung and inappropriate secretion of antidiuretic hormone (ADH) was not able to dilute his urine with a similar water load. These data suggest that the dilutional syndrome in severe myxedema is due to a resetting of the osmolar regulatory mechanism rather than inappropriate secretion of ADH. In the hydropenic studies during myxedema both Umax and T c H 2O per Cosm were reduced. During therapy the defects in renal function healed slowly and at different times. The GFR returned to normal quickly as the patients became clinically euthyroid. Later the diluting defect and capacity to concentrate the urine improved. The T c H 2O defect corrected last. Thus, the clinical assessment of return of thyroid function to normal may obscure the persistence of myxedema at a tissue or cellular level in the kidney and possibly in other organs.