For many years a few physicians have conceived of a condition the direct opposite of parathyroid tetany. Lundborg (53) and later Chvostek (21) believed this was manifest in myasthenia gravis but clinical observations did not confirm their belief. It was not until the use of Colip's (23) active parathyroid extract in animals had indicated the symptoms of such a state that hyperparathyroidism was recognizable as a clinical syndrome. It is now known that it constitutes a picture of disease as clearly defined as hyperthyroidism and follows closely the abnormalities which may be produced by parathyroid extract in animals. The literature and clinical features have been discussed in another paper (2).Many facts concerning functional abnormalities in hyperparathyroidism have already been determined. Colip (23) has shown that the various well-known manifestations following removal of the parathyroid gland are reversed after the parenteral administration of parathyroid extract. No longer is the theory tenable that the fall in serum calcium after parathyroidectomy is but a secondary phenomenon. Active extracts will prevent it and by raising the serum calcium entirely relieve the symptoms. Extracts readily cause an increase in the serum calcium in normal animals. It seems obvious now that the parathyroid glands are concerned with the regulation of the calcium concentration in the blood. They appear as an essential component in one of those remarkable regulatory mechanisms characteristic of the higher animals. The constancy of the serunrcalcium even under many of the most abnormal conditions is worthy of special emphasis. Although an increase in serum phosphate is typical of parathyroid tetany a reduction has not commonly been found in experiments in which parathyroid intoxication was rapidly produced. Robinson, Huffman and Burt (62), however, report a reduction in the serum phosphate of calves receiving parathyroid extract. Greenwald and Gross 143 HYPERPARATHYROIDISM (39) and later other investigators have definitely shown that effective parenteral administration of parathyroid extract causes an increased excretion and especially an increased urinary excretion of both calcium and phosphorus, phenomena quite the reverse of those following parathyroidectomy. A change in the tone and irritability of muscles which might be considered the opposite of tetany is suggested in the hypotonia often noted in animals with hypercalcemia. Berman (9) using galvanic currents has demonstrated a definite decrease in the electrical response in the peroneal nerve of normal dogs after a moderate increase of serum calcium produced by parathormone. These The following study of the functional pathology of the disease was started in April 1928, and has been continued to the present time. It will indicate the abnormalities encountered and will emphasize factors to be considered in diagnosis and treatment. MIETHODS OF STUDYThe patients with hyperparathyroidism were studied in the Metabolism Division of Barnes Hospital. Their diets were prepared in ...

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Rowe (17), in 1917, reported observations of the serum proteins of 10 patients with diabetes. The only remarkable thing was the extreme variability of the findings. Both high and low values were obtained. In the majority of instances albumin and globulin preserved their normal proportions; but in some instances globulin appeared relatively high. Subsequent observers have confirmed Rowe and the general opinion. appears to be that there is nothing characteristic about the serum protein level in diabetes.In table 1 are shown the results of 52 observations of the plasma proteins of 31 patients with diabetes mellitus of varying degrees of severity, studied at different stages of the disease. EXPERIMENTAL PROCEDUREWhenever there is no note to the contrary, the blood was taken in the morning, before the patient had breakfast and the morning dose of insulin. The blood was withdrawn in a syringe and coagulation prevented by the addition of enough neutral potassium oxalate to make an 0.2 per cent oxalate solution in the blood. The treatment of the blood is indicated in column 6 of the table. Those specimens marked cont. were obtained without stasis and immediately placed over mercury in a blood sampling tube of the type described by Austin, Cullen, Hastings, McLean, Peters and Van Slyke (1). Usually venous blood (ven.) was employed, but occasionally arterial (art.) was used instead. In specimens indicated as cap. the blood was withdrawn without precautions against air contact and brought into equilibrium with 40 mm. of CO2 in the air at 38°C. by the method previously described (16) before it was placed in the sampling tube over mercury. From the mercury sampling tube part of the blood was transferred to a centrifuge tube 451

In an earlier, rather extensive, publication in this journal on the "Functional Pathology of Hyperparathyroidism " (1) no mention was made of magnesium metabolism. Data have now been collected permitting a contribution to this phase of the subject. The methods of study were the same as described in the previous paper (1). Magnesium determinations were made by the procedure outlined by Briggs (2).The pharmacological relationship of calcium and magnesium ions and therefore the necessity for optimum concentrations of both in body fluids suggest a close association of the mechanisms regulating their level in the blood. The fact that magnesium phosphate has solubility properties similar to calcium phosphate and the fairly constant amount of magnesium in bone hint at a specific biological relationship of their compounds.It would seem that the parathyroid hormone might have at least an indirect influence on magnesium metabolism. The immediate effect of parathyroid hormone on serum magnesium has been studied in dogs by Scholtz (3) and by Greenburg and Mackey (4). Their investigations showed a slight increase in serum magnesium occurring early and before the rise in calcium. By the time calcium had reached maximum values the serum magnesium had fallen towards normal. Our experiments indicated that more prolonged administration of parathormone to dogs resulted in no striking alterations in serum magnesium (Table I). This was also true with rabbits in which parathormone is not very effective in raising the serum calcium.

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