Hypothalamus- Pituitary - Kidney Axis

Essentially almost by definition patients with GDD have normal/near normal renal function. Yet a number of individuals do have renal abnormalities, but not sufficient to cause renal failure, but I think possibly sufficient to cause subtle abnormalities in kidney handling of Gd. One such renal abnormality which I have observed in a few patients is medullary sponge kidney. Amongst other things, this abnormality has a high incidence of small calcified renal stones. Perhaps there is some Ca-Gd interaction in this condition.

Another phenomenon seen in a few patients is unexplained large urine output (medical term: polyuria). The most common condition that one observes polyuria, also combined with increased drinking (polydipsia) is type 1 diabetes. Some GDD patients have daily urine volumes of around 4 L, which is essentially exchanging out your total body serum daily - which is incredible when you think of that. Chelation in the setting of massive urine output, one would superficially think this is a great way to get rid of all the Gd left in the body. It appears though this is not the case that it is helpful in them - some of the most resistant to treatment patients are those with massive urine output.

The massive urine output may reflect an abnormality with AntiDiuretic Hormone (ADH). ADH is produced in the hypothalamus and stored in the posterior pituitary for release, and acts on the kidney. ADH causes retention of fluid; therefore some form of lack or dysfunction of ADH, which could originate in the hypothalamus, pituitary or kidney, would result in massive urine output. The situation seen in maybe 10% of GDD subjects.

Richard Semelka, MD