In the old days, when a patient started producing large quantities of urine, the doctor just stuck his finger in the urine and tasted it. If the urine tasted sweet, the patient had diabetes mellitus (= sweet flood). If the urine was not sweet, then the diagnosis was diabetes insipidus (= tasteless flood), and something was wrong with the kidneys or the brain.

Every day large quantities of blood pass through the kidney for cleaning purposes. During the cleaning process, the kidney recycles about 15 liters of fluid per day from the waste water. The kidney receives help with this from a brain hormone that inhibits the excretion of water, hence its name: “anti-diuretic hormone” (ADH). The same hormone is also known as “vasopressin” because it acts to raise the blood pressure. It is a small protein produced by the brain cells. These cells are located in the hypothalamus and transport the hormone to the rearmost part of the pituitary gland, where it enters the bloodstream.

Revolutionary

The idea that brain cells could produce hormones was first suggested in the 1940s by Ernst and Berta Scharrer. Under the microscope they saw grains in large brain cells in the hypothalamus, and proposed that they were packaged hormones ready for release into the bloodstream. This revolutionary concept aroused strong emotional reactions among their colleagues. “Practically everybody rejected the idea vigorously or even viciously” Berta wrote me, still angry as an elderly woman.

Opponents claimed the grains were just part of a disease process, or changes that occurred after death or produced by the staining process. The Scharrers showed that they were wrong by finding similar nerve cells with grains throughout the animal kingdom, from worm to human. Their hypothesis that these cells had something to do with the body’s water management system was visionary. The function of ADH immediately became clear when a hereditary defect in the DNA for this hormone was found. Such a patient urinates 15 liters per day.

In Amsterdam we have followed such a family for five generations. It was during my internship in 1968 in the Central Hospital in Prof. Borst’s department that I first met them. The life of this family was determined to a great extent by continuous urinating and drinking.

Excessive drinking and urinating

One patient said her mother, who also had diabetes insipidus, got fed up with all the urinating and drinking of the children sleeping with her in the same room. The children were strictly forbidden to get out of bed at night to drink something. But the mother always kept a kettle under the bed to slake her own thirst.

The children could not stand being without water, however. While the mother slept, they secretly crept under the bed to suck on the kettle’s spout. If they woke their mother, they were slapped. When one patient was admitted to a sanatorium as a child, the nursing staff found the excessive drinking and urinating so annoying that they refused to give her more water for a long time. To get enough fluid, the patient would drink the flower vases dry at night.

At a certain point she became so dehydrated that it was thought she would die. The parents arrived just in time to restore her with a large bottle of water. If she went bicycling with her sister, they always took bottles of water along. At petrol stations, each one would drink a bottle and then refill it for the road, leaving the station attendant open-mouthed.

In 1992 we found the tiny defect in the DNA of this Amsterdam diabetes insipidus family in collaboration with a research group from Hamburg. One building block of the DNA on chromosome 20 was responsible for the 15 liters of urine per day. Now the patients can administer long-acting ADH by nasal spray, which has reduced the quantities to be drunk and urinated to almost normal proportions. Some patients refuse to take the medicine, though. They don’t consider this condition a disease, but rather a special family trait.

Dit verhaal is geplaatst op vrijdag 27 maart 2009 om 14:28 uur.