The Mauriac syndrome: dwarfism, hepatomegaly and obesity with juvenile diabetes mellitus.

A triad of symptoms of varying degrees of dwarfism, hepatomegaly and obesity, developing slowly in diabetic children, has been commonly designated the Mauriac syndrome, after P. Mauriac's first descriptions published in 1930 and 1934'. Mauriac wrote that with the discovery of insulin a new disease was born: juvenile diabetes, with curious troubles and manifestations of endocrine disturbances not previously seen because these patients formerly did not survive. Most cases of socalled diabetic dwarfism were reported during the first fifteen years or so after insulin became available. Mauriac at first suggested that long continued administration of insulin might be responsible for the syndrome. Subsequently there has been general agreement that the syndrome develops only among "badly managed" patients and is not seen in children who from the start of their diabetes are given good diets with daily insulin dosage adequately regulated. The various symptoms associated with retarded growth in juvenile diabetes are now usually ascribed to nutritional deficiencies, and lack of insulin, rather than to metabolic derangements peculiar to the disease itself. But further questions arise with regard to predisposing factors that may lead to the development of this syndrome in some patients more easily than in others. Conceivably, each of the three major symptoms may be determined by independent factors that accompany the diabetic trait in an individual. The patients who display this triad of symptoms are usually described as "brittle" diabetics, hard to manage. Thus the records of poor control may be explained, if not excused, by the fact that the adjustment of insulin dosage for proper control was much more difficult in these patients than in others of the same age whose physiologic adjustments were better, under approximately similar instructions with regard to diet and insulin dosage. While the complete syndrome occurs rarely, a recent article by Darnaud and others on "les formes frustes" of the Mauriac syndrome (i.e. not fully developed and with mild manifestations) suggests that these derangements may exist more often than is generally recognized but follow an abortive course if appropriate therapy is offered. Granting this possibility, the physio-pathology of separate phases of the syndrome assumes greater interest in the absence of severe manifestations. The salient features chosen for discussion here are: Hepatomegaly, characterized by surcharge of the liver with fat or glycogen or both; dwarfism, possibly conditioned by pituitary deficiency, but with nutritional factors playing a leading role; obesity with moon face, possibly associated with oversecretion of corticosteroid hormones; hypersensitivity to quick-acting insulin and favorable responses to slow-acting insulin, possibly related to both pituitary and hepatic factors. Joslin states that prior to the introduction of protamine zinc insulin hepatomegaly was one of the outstanding complications of juvenile diabetes. Marble and others reported 60 cases in 1938, representing approximately six per cent of the juvenile diabetics coming to their clinic. All of these had records of poor control, frequent occurrence of ketosis and of hypoglycemic reactions from regular insulin with dosage poorly regulated. Following treatment with slow-acting protamine zinc insulin the liver decreased in size in 79 per cent of these cases. Hepatomegaly in the diabetic was at first thought to be due to fatty infiltration; later, many large livers of diabetic patients have been found surcharged with glycogen, some with both glycogen and fat. Lack of insulin is the most likely primary cause of fatty infiltration, but numerous investigators suggest that it may be caused or aggravated by a deficiency of lipotropic factors. While a nutritional deficiency seemed unlikely,