Mauriac syndrome: A rare complication of type 1 diabetes mellitus

Sir,

Mauriac syndrome is characterized by dwarfism, obesity and hepatomegaly in patients with insulin-dependent diabetes mellitus. It is associated with poor control of type 1 diabetes mellitus (T1DM) in adolescents, and may present as obesity, hepatomegaly, cushingoid facies and elevated transaminases.[1] It is typically associated with growth failure and delayed pubertal maturation, which should alert the physician over insufficient management of diabetes mellitus and the related development of Mauriac syndrome, although these can be reversed with good glycemic control.[2]

A 21-year-old male with a 10 year history of T1DM was admitted for evaluation of growth retardation, abdominal distension and diabetes. The patient was on pre-mixed insulin (30/70) - 0.8 unit/kg of body weight per day in two divided doses of 15 units and 10 units. He had poor control of diabetes with no regular follow-ups. There was no history of diabetic ketoacidosis, but multiple episodes of documented hypoglycemia were reported. There was no history of hypertension or family history of diabetes. Anthropometric data revealed height 137 cm (<3^rd percentile), weight 33 kg (<3^rd percentile), body mass index 17.58 kg/m², height age 10.5 years, weight age 11 years, bone age 7.3 years, upper segment 69 cm, lower segment 68 cm and arm span 136 cm [Figure 1].

Figure 1.

Child of type 1 diabetes and Mauriac syndrome

His intelligent quotient was 96 and his mental age was 14 years. Physical examination revealed hypertension (BP 170/120 mmHg on repeated recordings), moon facies, thin scalp hair, cold skin, high pitched voice, protuberant abdomen and hepatomegaly. The patient was prepubertal with tanner stage 1 for testicular and pubic hair development. There was no vitiligo or widely spaced nipples. Fundus examination revealed bilateral severe proliferative diabetic retinopathy with macular edema and grade 2 hypertensive retinopathy. Laboratory analysis revealed: Hemoglobin 11.6 g/dl, total protein 6.4 g/dl, albumin 3 g/dl, triglycerides 145 mg/dl, total cholesterol 261 mg/dl, High density Lipoprotein-cholesterol 42 mg/dl and Low density Lipoprotein-cholesterol 190 mg/dl, aspartate aminotransferase 21 U/L (5-45 U/L), alanine aminotrasferase 18 U/L (5-45 U/L) and ALP 172 KAU/dl. Serum calcium was 10.2 mg/dl and phosphorus was 5.6 mg/dl. His 24 h urinary calcium excretion was 54 mg, phosphorus excretion was 450 mg and creatinine excretion was 306 mg. Blood urea was 36 mg/dl and serum creatinine was 1.0 mg/dl. Serum sodium was 134 meq/l and potassium was 5.7 meq/l and serum osmolality was 275 mosm/kg. His 24 h urinary protein excretion was 1512 mg. His thyroid profile (free T3 (FT3), free T4 (FT4) and Thyroid stimulating hormone) was within normal limits. His anti-Thyroperoxidase antibodies were negative. Basal serum cortisol was 16.7 μg/dl and the standard short adrenocorticotrophic hormone-stimulated cortisol was 39.5 μg/dl and glycosylated hemoglobin was 13.5%. Celiac disease was ruled out with anti-transglutaminase negative. ultrasonography revealed Grade I fatty change of the liver and b/l kidneys showed increased cortical echogenicity. Radiological examination was normal.

Our patient presented with uncontrolled diabetes mellitus of 10 years duration. He had severe growth retardation, pubertal delay, hepatomegaly and diabetes-related microvascular disease (proliferative retinopathy and nephropathy). Based on these findings, a diagnosis of Mauriac syndrome was made.

Mauriac syndrome occurs in males and females equally, and is most common in adolescence, although there are reports in children as young as toddlers and in adults. It is associated with hepatomegaly and diabetic dwarfism. The actual cause is unknown, but it is probably a combination of factors including inadequate glucose uptake and utilization in the tissues, decreased insulin-like growth factor-1 and growth hormone levels, impaired bioactivity of these hormones, a circulating hormone inhibitor, resistant or defective hormone receptors, insulin deficiency, poor glycemic control, concurrent autoimmune diseases, decreased caloric intake and/or eating disorders. Autoimmune diseases that are more common include Addison's disease, autoimmune gastritis, celiac disease and hypothyroidism.[3] Before treatment with long-acting insulin, delays in growth and sexual maturity were common but generally modest; but, nowadays, with better treatment modalities, this syndrome is rarely seen.

Liver biopsy in the setting of Mauriac syndrome demonstrates steatosis and glycogen deposition, although findings can vary in presentation.[4] Poor T1DM control leads to fatty acid transport to the liver due to hyperglycemia and low insulin levels, which causes hepatomegaly and characteristic liver biopsy findings. These findings reverse with improved glycemic control.[5] Liver biopsy may be warranted in any patient with T1DM and positive autoimmune markers in order to rule out autoimmune hepatitis. The hepatomegaly seen in Mauriac syndrome is not seen in newly diagnosed patients who have been severely insulin deficient because it appears that periods of supraphysiologic insulin levels are associated with the hepatomegaly. Hypertension has never been reported in any of the previous cases of Mauriac syndrome, and, in our case, may be secondary to overt diabetic nephropathy.

To conclude, Mauriac syndrome is a rare complication of poorly controlled diabetes mellitus in adolescence, but the treating physician should keep a high index of suspicion for this so that proper growth can be accomplished with timely intervention.