The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinism.

OBJECTIVE

There has been much debate concerning the relative contribution of insulin resistance to the development of polycystic ovaries (PCO). We therefore aimed to assess ovarian morphology and insulin/androgen status in females with the hepatic glycogen storage diseases types Ia (GSD-Ia) and III (GSD-III), disorders associated with abnormalities of insulin secretion.

DESIGN

A cross-sectional study of ovarian ultrasonography, oral glucose tolerance tests (oGTTs) and single measurements of gonadotrophins and androgens were performed.

PATIENTS

Twenty-seven patients were evaluated: 13 with GSD-Ia, median age 11.2 years (range, 3.3-26.7) and 14 with GSD-III, aged 13.2 years (4.2-31.3). None had clinical signs of hyperandrogenism and only two of the 13 adults (15%) had menstrual irregularities. They were compared to 9 normal adult female controls, aged 21-28 years.

MEASUREMENTS

Ovarian morphology and volume were measured. Blood glucose and plasma insulin concentrations were measured at the beginning and end of a 2-hour oGTT. Single measures of LH, FSH, testosterone, dehydroepiandrosterone sulphate, androstenedione, IGF-I and SHBG were made on samples taken at the beginning of the oGTT.

RESULTS

In both GSD-Ia and III, all those older than 4.8 years of age had a polycystic ovarian appearance. Pre-pubertal GSD-Ia patients had lower basal and 2-hour blood glucose and plasma insulin concentrations than pre-pubertal GSD-III patients. In adults with GSD-Ia and GSD-III, although basal and 2-hour blood glucose concentrations did not differ, both basal and 2-hour plasma insulin concentrations were significantly higher than controls. Serum gonadotrophins, androgens, IGF-I and SHBG were mostly normal.

CONCLUSIONS

A polycystic ovarian appearance is a common finding in patients with glycogen storage disease even before puberty. In GSD-III and adults with GSD-Ia, this ovarian appearance was associated with hyperinsulinism, suggesting an aetiological link, but this was not the case in pre-pubertal children with GDS-Ia. Inborn errors of carbohydrate metabolism may act as useful models for examining control mechanisms of ovarian physiology and development.