Metabolic Diseases in Children

(Reading of Chairman Najjar’s paper.) Chairman Mallar.’ I have indicated to you that the alpha cells of the pancreas excrete the hyperglycemic factor. The practical value of this finding can only be measured by its possible hearing on the understanding and treatment of aberrations of carbohydrate metabolism. Dr. Irvine McQuarnie has lately found cases of hypoglycemia that showed absence of these cells. lhis finding is of great significance in future therapy of this condition. What may have taken years to recognize is now an accomplished fact. This we owe to the keen efforts and observations of Dr. McQuarnie who will flOW address us. Dr. Irvine .McQuarrie, Minneapolis: Dr. Najjar has covered the fundamental aspects of the interrelationships between hormones and enzymes involved in carbohydrate metabolism so thoroughly that I shall not need to comment on that phase of the subject in my discussion of the hypoglycemosis (hypoglycemic state), but will lean heavily upon our clinical and pathologic observations. Spontaneously occurring, persistent hypoglycemia of severe grade with such manifestations as repeated convulsions and attacks of coma, which may be followed by irreversible damage to the central nervous system if inadequately treated, is, fortunately, a comparatively uncommon disorder. On the other hand, milder forms of the condition, characterized by such symptoms as a vague sensation of hunger or gauntness, a feeling of faintness or weakness, cold sweats and other vasomotor reactions, tremulousness, dizziness, mental confusion, drowsiness and occasional convulsions, occur with far greater frequency than most physicians appreciate. It has been estimated by several authorities on the subject that the total number of persons in the United States who are afflicted with the syndrome is almost as great as the number known to suffer from diabetes mellitus. The complexity of the problems of etiology, classification, diagnosis and treatment of spontaneous hypoglycemia is illustrated by the schema presented in the first slide. The concept of the blood sugar concentration being dependent upon a balance between the functional activity of the insulinproducing system on the one hand and the combined activities of a series of hyperglycemia or antiinsulin factors on the other is expressed through the symbol of an old-fashioned steelyard provided with a modern pointer and scale. According to this concept, every case of spontaneous hypoglycemia is due to either absolute or relative hyperinsulinism. The expression, “true, or absolute hyperinsulinism,’ obviously implies therapeutic insulin overdosage or overproduction of insulin by the beta cells of the pancreas. While it is conceivable that normally appearing insular beta cells might produce excessive amounts of insulin at times in response to nervous or other extrapancreatic stimuli, the evidence that this is an important cause of spontaneous hypoglycemia in any but the mildest cases is not entirely convincing. Tumors (adenoma and carcinoma) and hyperplasia, involving the beta cells of the pancreatic islands. constitute the only satisfactorily demonstrated pathologic lesions associated with absolute hypeninsulinisni. Successful surgical excision of a benign islet tumor results in complete cure of the hypoglycemosis. Such tumors are extremely rare in children. Subtotal pancreatectomy in cases showing islet hyperplasia is frequently highly beneficial, at least temporarily. Alloxan used by Talbot and coworkers as a last resort in one severe case of hyperinsulinism appeared to give satisfactory results. Because of its marked hepatotoxic and nephrotoxic action, this agent should obviously be used with extreme care if used at all. The term “relative hyperinsulinism” refers to the state in which hypoglycemia results from