797

ABSTRACTS M. A. GOLDZIZHER, S. SHERMAN AND B. B. ALPE~STEIN.

Endocrinology. The Fat Tolerance Test in Pituitary Disease. 18:505-512, J~tly-August, 1934. A fat tolerance test has been devised to demonstrate the functional state of the anterior lobe of the hypophysis as measured by the physiologic discharge of a f a t metabolism hormone. The "measuring-rod" is the level of the blood acetone after ingestion of a f a t test meal. It is the opinion of the authors after use of the test meal in 109 cases, that almost all of the 56 patients in whom there was an absence of the physiologic rise of blood acetone bodies after the test meal were affected with pituitary deficiency. The authors believe that the consistent combination of a low specific dynamic action, high uric acid and increased f a t tolerance characterizes pituitary insufficiency. Dwight L. Wilbur, Rochester, Minnesota. E. H. RYNEARSON, M.D.

Hyperinsulinism; the Misuse of the Term. Proceedings of the Staff Meetings of The Mayo Clinic, Vol. 9, No. 39, September 26, 1934. "Seale Harris, in 1924, first suggested the diagnosis of hyperinsulinism, but it was not until 1927 that Wilder and his associates reported the first proved case, that of a surgeon, suffering from acute attacks of severe hypoglycemia, who was found at operation to have a carcinoma arising from the islands of Langerhans, with multiple metastatic growths from which large amounts of insulin were obtained. Since that time, many papers and reports of cases have been published under the general title of "Hyperinsulinism". Because of the importance of this interesting subject, and because of the many different syndromes which are being grouped under this term, it is well to define it. By hyperinsulinism is meant a condition wherein hypoglycemia is caused by excessive production of endogenous insulin. Many cases have been reported in which this insulin was produced by a tumor of the islands of Langerhans, and some patients have been returned to health by removal of such a tumor. This history of such a patient is clear-cut and diagnostic, and can be illustrated by the first of the following reports of cases. R E P O R T OF C A S E S W I T H C O M M E N T S

Case 1 - - A laborer, forty-five years of age, had been in good health until four years before his admission to the Mayo Clinic. At that time he had begun to have symptoms resembling those of drunkenness. These had appeared between meals, had been much more likely to occur if he had worked hard, and had been relieved by taking food. On one occasion he had had a characteristic epileptiform seizure, followed by unconsciousness which had lasted sixteen hours. When he awoke, he had been mentally confused until he had drunk some milk, when his condition rapidly had become normal. About this time he and his friends had realized the value of food in relieving these symptoms, so that on another occasion, when he had been unconscious for twenty-six hours, a friend had revived him by forcing him to drink milk. He complained of a severe headache, in conjunction with these symptoms, which had persisted in varying forms through the entire four years. The clinical diagnosis of spontaneous hypogIycemia was confirmed by a reading for blood sugar of 30 rag. per 100 c.c. At operation, a tumor of the island cells of the pancreas was discovered and was diagnosed carcinoma. Immediately following the operation, the concentration of sugar in the blood returned to normal, and hypoglycemia

never recurred. The patient has been in excellent health and never has had symptoms of any sort since his operation in 1931. Comment on Case 1, and on two cases of a puzzling type: In the history there are several important features: the patient's symptoms were present only when he was hungry, they often were produced by exercise, they were essentially of neurologic character, they were relieved by ingestion of carbohydrate, and they disappeared entirely following surgical removal of an adenoma of the island cells of the pancreas. Hyperinsulinism is only one cause of spontaneous hypoglycemia. Other causes are listed by Wauchope as follows: 1.--Excess of insulin. This may be the result of therapeutic injections of insulin, of tumors and hyperplasia of the pancreas, or of functional hyperinsulinism (idiopathic hypoglycemia). 2.--Lack of opposing secretions. This condition may result from disease of the suprarenal glands, from tumors of the anterior or posterior lobe of the pituitary body, or from myxedema. 3 . - Lack of glycogen. This lack may result from destruction of reservoirs, from disease of the liver or wasting of muscles, from abnormal secretion of sugar, from renal diabetes, from lactation, from active depletion of stores such as occurs in muscular exercise, and from failure to replenish stores as in starvation. 4.--Interference with regulating center. This may result from a nervous disease which affects the pons, or from overaction of the vagus nerves. It can be seen that anything which interferes with any step in the complicated mechanism of carbohydrate metabolism may produce hypoglycemia. Judd, Kepler and I have described hypoglycemia caused by p r i m a r y pathologic changes in the liver and J. Wilder has attributed the condition in two cases to lesions in the pituitary body. Unfortunately, the latter cause was not completely proved. The group which is causing most confusion is illustrated by the cases of which reports follow: Case 2 - - A woman was first admitted to the Mayo Clinic in 1912, when she was twenty-four years of age. At t h a t time, a diagnosis of "neurosis" had been made. She was readmitted August 30, 1934, with the history that she had had average good health, except for symptoms of cholecystitis, until 1926 when migraine had developed. In 1929, following an attack of mumps, she had complained of weakness, tremor, dizziness and fatigue. In 1930 following her husband's death, her symptoms had increased in severity. In 1931 attacks had begun to develop which had consisted of blurred vision, sleepiness, weariness, numbness, palpitation of the heart, and mental confusion. T]~e symptoms had had no relation to meals and hot cocoa had been the only food to effect relief. In January, 1932, she had had a severe attack of gallstone colic. At about this time, because of the nature of her complaints, her physician had suspected hyperinsulinism. Readings of glucose tolerance at the third hour had been respectively 50 and 60 rag. per 100 c.c. of blood, on two determinations. No determinations of blood sugar had been made during an attack. Because of the evidence related and the chronic cholecystitis, operation had been performed elsewhere in February, 1932, at which time the gall bladder and part of the pancreas had been removed. Six weeks later a reading of glucose tolerance at the third hour had been 100 rag. per 100 c.c. of blood. The woman had felt somewhat improved until June, 1932, when her mother had died and her attacks had returned. These had continued intermittently thereafter. Examination at the Mayo Clinic gave essentially negative results except that renal glycosuria was discovered

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The value of blood sugar f a s t i n g was 98 mg. per 100 c.c. and the reading of glucose t o l e r a n c e at the third hour was 66 mg. per 100 c.c. She was dismissed with advice as to how to relieve her chronic nervous exhaustion. Case 3.--This patient, a man, first had come to the Mayo Clinic in 1920 at the age of thirty-two years, because he had been rejected for enlistment in the army on account of the presence of a goiter. None had been found, and his complaints, largely of weakness, had been felt to be on the basis of neurosis. The patient returned September 12, 1934, to report that shortly a f t e r he had left the Clinic in 1920 the attacks of weakness had become more pronounced; he gradually had noted their occurrence when he was hungry, and he had obtained relief by eating. These attacks had consisted of exhaustion, generalized aches and pains, dyspnea, sweating, dizziness on stooping over, salivation and mental confusion. F o r years before his admission he had been eating six to seven meals a day, but as he had not had trouble during the night he had not had to resort to nocturnal feedings. In March, 1930, he had consulted a physician who had obtained a glucose tolerance curve and had found the reading at the third hour to be 48 mg. per 100 c.c. A diagnosis of hyperinsulinism had been made, and the patient had been advised to have an exploratory operation on the pancreas. He had refused; he then had been advised that it was dangerous for him to continue as a machinist. He thereupon had begun selling papers but his attacks had continued. On the patient's admission to the Mayo Clinic his reading of glucose tolerance at the third hour was 65 mg. per 100 c.c. The value for blood sugar, fasting, was 90 mg. per 100 c.c. and he was advised not to eat until his blood sugar level had been determined. Such determinations were made at intervals, and at no time was hypoglycemia found. Without his having taken any food for twentyeight hours, the concentration of blood sugar was still 90 rag. per 100 c.c. Accordingly, the opinion was reached that his symptoms were functional and not th~ result of hyperinsulinism, and he was advised to return to his usual occupation. Because of his frequent desire for food, roentgenologic examination of his stomach and duodenum was carried out and a duodenal ulcer was found, for which medical measures were prescribed. G E N E R A L COMMENT In Cases 2 and 3, the history was too long for a tenable diagnosis of hyperinsulinism, the fasting value for blood sugar was normal, the patients did not experience difficulty without taking food at night, and in Case 2 definite relief was not obtained from eating. I am of the opinion t h a t patients of this type should not be said to have hyperinsulinism. Neither the history nor the findings are suggestive of overproduction of insulin. The underlying condition responsible for production of this syndrome is not definitely known, but it is probably a manifestation of a vagotonic disturbance. A t the Clinic we have chosen to call this "functional hypoglycemia" to distinguish it f r o m the group of cases of organic hypoglycemia caused by hyperinsulinism, cirrhosis of the liver and so forth. There are repeated references in the literature to sugartolerance curves as being suggestive, or typical of hyperinsulinism. There is no such thing as a suggestive or typical curve. In some of our most severe cases of proved hyperinsulinism, normal or diabetic sugar-tolerance curves, and low values for blood sugar at the third hour of the sugar tolerance test are found in an appreciable number of cases in which there is no suggestion of hypoglycemia. In one year, more than twenty patients were found to have a reading for blood sugar at the third hour of 60 mg. per 100 c.c. or less. In conclusion, I do not believe that the term hyperinsulinism should be made a waste-basket for vague and

poorly defined conditions in which mild hypoglycemia, or an unusual glucose-tolerance curve, is a part of the picture rather than a cause of it." F r a n k Smithies, Chicago. YOSHIO ASODA.

Significance of the Liver in the Metabolism of Lipoid Bodies. Changes in Lipoid Bodies in the Blood and Bile When Various Kinds of Bile Acids Are Admlnistered. Japanese Journal of Gastroenterology, Vol. VI, No. 1; April, 1934. The study was suggested by the observation that liver disease brings about a definite change in the lipoid bodies in the blood and bile and that lecithin injected is not excreted by the pathological liver ,but is retained in t h e blood. Experiments were carried out to show the effect of the various bile acids in connection with the f a t content of bile and blood. The peroral administration of bile acids to rabbits brings about, as a rule, a temporary decrease in lecithin, total cholesterol and total f a t t y acids in the blood. Continuous administration of bile acids also provokes a gradual diminution in these f a t t y bodies except that the total f a t t y acids present a temporary increase in the early period of the administration. Various kinds of bile acids were administered by mouth to rabbits with the following conclusions: 1. Lecithin, total cholesterol and total f a t t y acids a r e decreased in the blood. 2. Lecithin, total cholesterol and total f a t t y acids in the bile are increased in both concentration and amount. 3. The quantitative .changes in lecithin and total cholesterol are parallel with each other in the blood and the bile. 4. These results are irrespective of the kind of the bile acid. 5. These facts corroborate the idea that the liver regulates the amounts of lipoid bodies in the blood by the control of their excretion into the bile. V. C. Rowland, Cleveland, Ohio. ACHARD, PROF. CH. ; LEVY, JEANNE, Rrr GEORGIAKIS,N.

The Cholesterol of the Food. Arch. des Mal. de l'App~ digestim et des real. de la Nutrition, Paris, Octobre, 1934. A f t e r an extensive review of the important r61e played by the cholesterol in pathology, the authors, although believing it increases in the body when the diet is rich in cholesterol, claim that there exists a systemic r e g u l a tion of the cholesterol depending on a physico-chemical phenomenon independent from the synthesis of this body. I t is most likely of exogenous origin. There appears t o be a cycle according to which the vegetable cholesterol is converted into phytosterol to become secondarily an animal cholesterol, when assimilated by the latter. And finally is eliminated as coprosterol. Hypercholesterolemia may be alimentary or digestive. When digestive, its formation is slow. Still, the seat o f the synthesis remains unknown. The cholesterol-rich diets being obviously forbidden to the patients suffering from a cholesterolemia, the authors have made a survey of the quantity of cholesterol contained in various foodproducts, by an improved original method. The lipoids of the same products have also been calculated. To give an idea of a long list we point out the f e w following food-products as containing a high cholesterol content: milk, table butter (0.760 per 1000), olive oil, fresh cream, cream cheese, most of the cheeses, veal and mutton kidneys, calf's liver, calf's brain (19. per 1000), the yolk of the eggs (17.540), shrimps, oysters, brioches, peas, fresh nuts, peanuts, chestnuts, almonds and chocolate. Jean R. A. Le Sage. Montreal, Canada.