New Hampshire. A urinary level of 0.09 mg. of mercury per liter, with a urinary specific gravity of 1.004, confirmed the clinical diagnosis. (Normally, no mercury is found in the urine; the hazard level for industrial workers is 0.20 mg. of mercury per liter, with a specific gravity of 1.024.) The patient was referred to the Massachusetts General Hospital for further evaluation and treatment.
Upon admission he had the typical symptoms and signs of acrodynia. These included complaints of pain in the abdomen, extremities and joints, irritability, swinging changes of mood, a marked degree of photophobia, increased perspiration, desquamation and pink color of the hands (Fig. 1), hypertension, hypotonia, salaam positioning (Fig. 2), anorexia and insomnia. His weight was 17 kg., and the body-surface area 0.7 square meter.
Laboratory studies included a normal hemogram and normal electrolytes, blood urea nitrogen, albumin, globulin, serum glutamic oxalacetic transaminase and alkaline phosphatase. An L.E.-cell preparation was negative.
Lumbar puncture revealed a normal spinal-fluid pressure, protein, sugar and colloidal-gold curve. An electroencephalogram was interpreted as being a moderately abnormal waking record because of asymmetry of the 2 sides. There was poor driving and response to strobe on the left. A repeat electroencephalogram 3 days later revealed no marked change.
X-ray films of the skull, knees, shoulders and an intravenous urogram* were normal. X-ray study of the teeth revealed extensive caries involving the deciduous teeth, and several permanent teeth were loose.
Urinalysis was within normal limits. The urine contained trace amounts of lead, but no protein or arsenic. The creatinine clearances were 53 and 54 liters per day. The 24-hour urinary coproporphyrin excretion was normal. Catechol amine studies, done because of clinical signs of increased sympathetic activity, showed a urinary excretion of 3 microgm. of epinephrine and 79 microgm. of norepinephrine per 24 hours. The vanilmandelic acid excretion was 3.5 mg. per 24 hours.
Urine specimens were quantitatively analyzed for mercury throughout the course of the patient’s illness with the use of a modification of the Monkmon method.22 Samples of urine were cold digested with potassium permanganate and sulfuric acid to destroy the organic material. The excess potassium permanganate was bleached with hydroxylamine hydrochloride, and after adjustment to a pH of 6, the solution of the soluble divalent mercury was passed through a glass filter impregnated with cadmium sulfide. The mercury in solution was retained on the pad as a sulfide. The sulfide was then placed in a flask and heated. Evolved mercury was drawn through a General Electric Mercury Vapor Detector, and the readings plotted at 10-second intervals. Standard urines containing known amounts of mercury were treated in a similar manner, and the readings compared with that of the unknown solutions. (The method is very sensitive and is reproducible to less than 0.1 microgm. of mercury per aliquot.)
The patient was treated with N-acetyl-D,L-penicillamine,* 0.125 gm. given 4 times a day (30 mg. per kilogram of body weight per day). The urinary excretion of mercury is shown in Figure 3. The mercury levels of the urine samples rose with treatment, diminished upon discontinuation and were again elevated with the reinstitution of treatment. The daily clinical course, emphasizing change in blood pressure, frequency of abnormal posturing, photophobia and redness and desquamation of the hands, is charted in Figure 3. There was some increase of pain, a slight increase of erythema of the palms, more frequent salaam posturing and greater fluctuation of mood when therapy was discontinued.
With N-acetyl-D,L-penicillamine therapy the patient showed general improvement except for his behavior. This became progressively worse as evidenced by refusal to eat, lying on the floor, throwing away urine specimens and great fluctuation in mood. However, when he was informed of his impending discharge, his behavior became much improved. A follow-up electroencephalogram had reverted to normal.
At home his behavior again became a problem, necessitating readmission 11 days after discharge. He was given a 6-day course of N-acetyl-D,L-penicillamine. His behavior markedly improved although there was no significant increase in the urinary mercury excretion. After 8 days in the hospital he was discharged, and since this last discharge he has maintained his clinical improvement. Ten months later a urine sample contained 0.016 mg. of mercury per liter.