title: Follow-up study of two sisters with type A syndrome of severe insulin resistance gives a new insight into PCOS pathogenesis in relation to puberty and pregnancy outcome: a case report.
abstract: We report two sisters with profound insulin resistance associated with a novel heterozygous missense mutation in exon 19 (His1130Arg) of the insulin receptor gene. The eldest was seen after puberty at age 15 and she presented a severe form of polycystic ovary syndrome (PCOS) with biological hyperandrogenism (HA) mimicking a virilizing tumour. However, she has been able to ovulate under clomiphene citrate (CC) and to achieve two uneventful pregnancies. The patient had no glucose tolerance abnormality during pregnancies. The outcome of pregnancy was good except for a low birthweight. The youngest sister was seen earlier in life (at age 11) before puberty. First, she developed polycystic ovaries (PCO), seen under ultrasound scan, and later also developed full PCOS. This second finding gave us the opportunity to observe that PCO developed before and at the beginning of puberty despite low LH levels. We postulate that the development of PCO was the consequence of an LH-independent intra-ovarian HA likely induced by the severe hyperinsulinism in the context of genetic abnormalities.
authors.affiliation: Department of Endocrinology and Diabetology, Clinique Marc Linquette, Hospitalier Régional Universitaire, Lille, France. a-vambergue@chru-lille.fr
authors.forename: A
authors.initials: A
authors.lastname: Vambergue
authors.forename: C
authors.initials: C
authors.lastname: Lautier
authors.forename: A S
authors.initials: AS
authors.lastname: Valat
authors.forename: C
authors.initials: C
authors.lastname: Cortet-Rudelli
authors.forename: F
authors.initials: F
authors.lastname: Grigorescu
authors.forename: D
authors.initials: D
authors.lastname: Dewailly
mesh_terms: D000293:Adolescent; D002996:Clomiphene / Q000008:administration & dosage; D005091:Exons / Q000235:genetics; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage; D006579:Heterozygote; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D050498:Live Birth; D007986:Luteinizing Hormone / Q000378:metabolism*; D020125:Mutation, Missense; D010060:Ovulation / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011627:Puberty / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics*; D035781:Siblings; D013577:Syndrome
chemical_list: D005300:Fertility Agents, Female; D007328:Insulin; D002996:Clomiphene; D007986:Luteinizing Hormone; D011972:Receptor, Insulin