hepatomegaly and elevated liver enzyme levels in type 1 diabetes mellitus ( dm ) patients can be caused by hepatic glycogenosis , viral hepatitis , autoimmune hepatitis , or metabolic liver diseases .
mauriac syndrome is a rare complication of type 1 dm that is characterized by hepatomegaly due to hepatic glycogenosis , growth retardation , delayed development of puberty , and cushingoid features .
it is caused by abnormal hormone secretion and metabolic abnormalities because of inappropriate glycemic control1 ) .
if the insulin dosage is insufficient to control hyperglycemia , it can stimulate hepatic glycogenosis and fatty acid synthesis , resulting in inhibition of glycogenolysis and hepatomegaly .
hepatic glycogenosis in type 1 dm patients is a reversible complication by strict blood glucose level control , which is different from nonalcoholic steatohepatitis ( nash ) in obese type 2 dm .
thus far , eight cases of type 1 dm accompanied by hepatic glycogenosis and three cases of mauriac syndrome have been reported in korea234 ) .
we report a case of hepatic glycogenosis mimicking mauriac syndrome in a patient with poorly controlled type 1 dm who showed hepatomegaly , cushingoid face , mild growth retardation , and delayed menarche .
a 14-year - old girl was admitted to the catholic university of korea , seoul st .
total daily insulin dosage was 12 iu ( 0.26 iu / kg / day ) .
she had previously been admitted seven times because of diabetic ketoacidosis in the previous 2 years . at the time of admission , the patient had clear consciousness , with the following vital signs : blood pressure , 90/60 mmhg ; pulse , 118/min ; and body temperature , 36.5. the height of the patient was 155 cm , and her weight was 46 kg , which were in the 25th and 50th percentiles , respectively .
growth velocity decreased to 3.3 cm / yr in the past 2 years ( fig .
the patient presented with tanner stage iv breast and tanner stage iii pubic hair ; however , the patient did not experienced menarche .
bone age was delayed by 2 years compared to her chronological age . upon physical examination
blood test results revealed the following values : white blood cells , 4,840/mm ( 47.5% neutrophils and 42.6% lymphocytes ) ; hemoglobin , 13.4 g / dl ; platelets , 218,000/mm ; aspartate aminotransferase ( ast ) , 1,408 iu / l ; and alanine aminotransferase ( alt ) , 459 iu / l ; gamma glutamyltransferase , 430 iu / l ; and amylase , 115 iu / l . the glycosylated hemoglobin ( hba1c ) level was 14.3% , and ketone was not detected in urine . to rule out viral hepatitis ,
we performed serologic tests for hepatitis a , b , and c ; epstein - barr virus ; and cytomegalovirus infections , and obtained negative results .
furthermore , the results of autoimmune hepatitis , including antinuclear antibody , antismooth muscle antibody , and antiliver kidney microsome antibody , were all negative .
thyroid function was normal and the following hormone levels were presented : insulin - like growth factor-1 ( igf-1 ) , 203 ng / ml ; luteinizing hormone ( lh ) , 4.47 miu / ml ; follicle - stimulating hormone ( fsh ) , 4.77 miu / ml ; and estradiol ( e2 ) , 35.44 pg / ml . the plasma cortisol level was 5.73 g / dl and the adrenocorticotropic hormone level was 17.14 pg / ml at 8:00 am .
3 ) . through a liver biopsy , we found ballooning degeneration with nuclear vacuolization of hepatocytes ( fig .
hepatocytes were strongly positive in a periodic acid - schiff ( pas ) stain ( fig .
4b ) , and such positive finding disappeared with diastase ( d - pas ) ( fig .
the insulin dosage was gradually increased over 3 months ; thus , the total daily insulin dosage became 36 iu ( 0.65 iu / kg / day ) .
to prevent hypoglycemia , we prescribed 60 g ( 1.3 g / kg ) of uncooked cornstarch between meals and bedtime . after implementing strict glycemic control , hepatomegaly was improved and elevated transaminase levels returned to normal ranges .
moreover , the patient manifested menarche at the age of 15.3 years and a regular menstruation cycle thereafter .
hepatic glycogenosis in type 1 dm is a key mechanism of mauriac syndrome and is a rare diabetic complication first reported by mauriac in 19305 ) .
hepatic glycogenosis can be caused by either a persistent hyperglycemia due to insulin deficiency or conversion of excess glucose administered to control hypoglycemia due to excessive insulin administration . with regard to the latter mechanism ,
furthermore , the secretion of the antagonistic hormone cortisol increases in type 1 dm patients with poor glycemic control . such excess cortisol inhibits hepatic glycogenolysis and increases fatty acid synthesis in the liver , causing hepatomegaly .
moreover , hypercortisolism can result in cushingoid features and delay in bone maturation , which in turn leads to delayed growth and puberty1 ) .
growth retardation and delayed puberty with hepatic glycogenosis in uncontrolled type 1 dm patients are distinct characteristics of mauriac syndrome . in patients with mauriac syndrome , circulating igf-1 levels are normal or reduced despite normal hypothalamic - pituitary functions .
patients with mauriac syndrome also exhibit resistance to growth hormones , which is caused by a decrease in igf-1 bioactivity , igf-1 receptor defects , and circulating igf-1 inhibitors9101112 ) .
delayed puberty can manifest as a result of insulin deficiency , hyperglycemia itself , or decreased lh and fsh secretion caused by the gonadotropin - releasing hormone due to stress hormone secretion after poor glycemic control .
insulin administered to the subcutaneous tissue bypasses the hepatic first - pass metabolism and is absorbed directly via systemic circulation .
then , the insulin binds with the receptor at the ovary to excessively stimulate the ovary , thereby increasing androgen secretion .
if peripheral insulin resistance increases because of hyperglycemia , polycystic ovary syndrome can occur , causing ovarian failure and amenorrhea1314 ) .
although growth retardation and delayed puberty were not prominent in our patient , the patient exhibited very similar clinical manifestations of mauriac syndrome .
the reason that the signs of growth retardation and delayed puberty were mild in our patient was probably because hepatic glycogenosis occurred in the late stage of pubertal development , thereby only minimally affecting the patient 's growth and puberty . as we did not measure 24-hour urinary free cortisol levels and the 8:00 am .
if the symptoms of mauriac syndrome recur , a detailed evaluation of hypercortisolism will be necessary
. treatments of hepatic glycogenosis in type 1 dm include strict glycemic control through appropriate diet and insulin dosage .
although regular diet and sufficient insulin dosage are important in controlling hyperglycemia , determining the appropriate insulin dosage is difficult when hyperglycemia is accompanied by frequent hypoglycemia , as in the case of our patient .
as glycogenolysis does not properly occur even with hypoglycemia in the patient with hepatic glycogenosis , additional glucose supply is necessary .
however , the glycemic effects of conventional snacks only manifest 2 hours after consumption . moreover , as the glycemic effect inevitably decreases with time , hypoglycemia can recur .
consequently , consuming uncooked cornstarch to induce delayed glycemic effects facilitates the prevention of hypoglycemia15 ) .
hepatic glycogenosis does not occur in all patients with type 1 dm who have poor glycemic control .
although the risk factors of hepatic glycogenosis are not yet known , we postulate that wide fluctuations of blood glucose levels and a long period of poor glycemic control increase the risk of hepatic glycogenosis .
however , hepatic glycogenosis in type 1 dm is a reversible complication that is different from nash , which is often presented in obese type 2 dm patients .
therefore , appropriate glycemic control is important to the treatment and prevention of hepatic glycogenosis in type 1 dm .
 hepatic glycogenosis in type 1 diabetes mellitus ( dm ) can be caused by poor glycemic control due to insulin deficiency , excessive insulin treatment for diabetic ketoacidosis , or excessive glucose administration to control hypoglycemia . 
 mauriac syndrome , which is characterized by hepatomegaly due to hepatic glycogenosis , growth retardation , delayed puberty , and cushingoid features , is a rare diabetic complication . 
 we report a case of hepatic glycogenosis mimicking mauriac syndrome . a 14-year - old girl with poorly controlled type 1 dm 
 was admitted to the catholic university of korea , seoul st . 
 mary 's hospital for abdominal pain and distension . 
 physical examination revealed hepatomegaly and a cushingoid face . 
 the growth rate of the patient had decreased , and she had not yet experienced menarche . 
 laboratory findings revealed elevated liver enzyme levels . 
 a liver biopsy confirmed hepatic glycogenosis . 
 continuous glucose monitoring showed hyperglycemia after meals and frequent hypoglycemia before meals . to control hyperglycemia , we increased insulin dosage by using an insulin pump . 
 in addition , we prescribed uncooked cornstarch to prevent hypoglycemia . 
 after strict blood glucose control , the patient 's liver functions and size normalized . 
 the patient subsequently underwent menarche . 
 hepatic glycogenosis is a complication of type 1 dm that is reversible with appropriate glycemic control . 