Mauriac Syndrome as a Rare Cause of Primary Amenorrhea: A Case Report

Introduction: longstanding poorly controlled hyperglycemia in children with diabetes mellitus type 1 may be presented by growth failure, short stature, delayed pubertal maturation, moon faces and liver enlargement associated with glycogen deposition; a rare complication of diabetes mellitus type 1 described as Mauriac syndrome. These processes can be reversed with good glycemic control. Case Report A 19-year-old female referred to our clinic for evaluation of primary amenorrhea. She has 10 years’ history of t1 DM and has been on an insulin regimen. The hypothyroidism was recognized since 2 years ago. Her mother had died when she was 6 years old, her father has married again and left them thereafter she lives with her 10 years older brother so therapeutic adhesion is not easy to achieve for her and she had a previous history of poor glycemic control. The puberty started 4 years ago but she never experienced vaginal bleeding.On examination she weighed 41.5 kg, she was 150 cm tall and had a BMI of 18.4 kg/m2 and she was normotensive. She had moon face and the puberty stage was P4B4.The investigations indicated a normal renal function, normochromic normocytic anemia and poor glycemic control, and elevated liver enzymes. HbA1C:13%, FBS: 530mg/dl, AST:124 IU/l, ALT:234 IU/l, blood gas analysis, and serum electrolytes were within normal limits and ketones were negative. Other hormonal axes analyses showed: TSH> 100IU/ml, LH: 4mIU/ml, FSH: 3.8mIU/ml, estradiol: 47pg/ml, cortisol (8AM):19.9microgr/dl. Autoimmune hepatitis markers (antinuclear antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, anti-liver-kidney-muscle) and viral markers (anti-HAV, anti-HCV, and HBS Ag) were negative. The abdominal ultrasonography showed mild hepatomegaly with fatty infiltration, a normal size spleen, a65*28mm uterus, and 10mm right ovary and left one was 8mm without a prominent follicle. Based on history, laboratory and sonographic findings, the diagnosis of Mauriac syndrome was suspected and the insulin regimen was adjusted and treatment with levothyroxine was restarted.Discussion: The syndrome was first described by Mauriac in 1930 characterized by liver enlargement from glycogen deposition and abnormal liver enzymes associated with growth and puberty delay in children with uncontrolled type 1 diabetes mellitus. Pathogenesis of the syndrome is not clearly understood but thought to be multifactorial. The genetic cause has been suggested which together with large amounts of plasma glucose and insulin may contribute to the development of glycogenic hepatopathy. In the setting of poorly controlled diabetes in hyperglycemic periods, glucose enters freely into the hepatocyte and stored as glycogen. Furthermore, hyperinsulinization due to higher amounts of insulin administration activates glycogen formation by glucokinase and glycogen synthase in the liver.On the other hand, high cortisol levels that occur after frequent hypoglycemic episodes as hypoglycemia counter-regulatory hormone and/or ketosis due to the absence of insulin in DKA episodes which cause lipolysis and ketone formation may lead to hypogonadism and growth retardation. Also a combination of factors probably contributes to delayed growth and puberty including inadequate glucose uptake and utilization in the tissues, decreased insulin-like growth factor-1 and growth hormone levels, target organ resistance to these hormones, insulin deficiency, poor glycemic control and recurrent acidosis, poor nutritional status concurrent autoimmune diseases such as Addison’s disease, celiac disease and hypothyroidism.Conclusions: This is a case of a young female with poorly controlled DM type 1, short stature, delayed puberty, hepatomegaly, and primary amenorrhea due to Mauriac syndrome. These manifestations may relate to various pathophysiologic mechanisms, such as poor nutritional status, inadequate glucose to the tissues, chronic intermittent acidosis, hypercortisolism, hypothyroidism, impaired calcium balance, and target organ resistance to either GH or IGF.