Serum levels of adiponectin differentiate generalized lipodystrophies from anorexia nervosa.

PURPOSE: The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy. METHODS: Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects. RESULTS: Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN. CONCLUSION: Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN.

Disorders of sexual development with XY karyotype and female phenotype: clinical findings and genetic background in a cohort from a single centre.

PURPOSE: 46, XY disorders (or differences) of sex development (DSD) are a group of clinical conditions with variable genetic background; correct diagnosis is often difficult, but it permits to optimize the management. The aim of this study is to identify clinical and genetics features of a group of women with 46, XY DSD to define some issues characterizing people with 46, XY DSD in Italy. METHODS: Retrospective analysis of girls and women with 46, XY DSD and female phenotype evaluated between year 2000 and 2016, performed by anonymised database, focusing on the clinical features and management, including presentation, first diagnostic suspect, gonadal surgery and molecular diagnostic delay. RESULTS: A total of 84 records were collected (mean age at clinical presentation: 9.1 ± 7.9 years; mean age at definitive diagnosis: 20.1 ± 15.0 years). Complete androgen insensitivity syndrome was the most common diagnosis (60%). Only 12 patients (14.3%) did not receive a molecular diagnosis. Early misdiagnoses frequently occurred; diagnostic delay was 10.2 ± 11.2 years, being reduced in patients presenting from 2007 to 2016. The discordance between genotypic and phenotypic sex during pregnancy or at birth determined early reason for referral in a considerable percentage (4.9%). CONCLUSION: Misdiagnosis and long diagnostic delays are present in females with 46, XY DSD in Italy, but the new genetic techniques permit faster right diagnoses in the last years. The centralization in dedicated third level units permits to reduce the number of patients without a molecular diagnosis, allowing better clinical management and appropriate genetic counselling.

17ß-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up.

BACKGROUND: Deficiency of 17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is a rare autosomal recessive 46,XY disorder of sex development (DSD). It is due to pathogenetic variants in the HSD17B3 gene. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Δ4-androstenedione (Δ4-A) to testosterone (T) in the fetal testis. Affected individuals are usually raised as females and diagnosis is made at puberty, when they show virilization. METHODS: A girl with a presumptive diagnosis of complete androgen insensitivity syndrome underwent endocrine and genetic assessment. Long-term follow-up was reported. RESULTS: The diagnosis of 17ß-HSD3 deficiency was made (stimulated T/Δ4-A ratio: 0.15; HSD17B3 gene analysis: c.277+4A>T in intron 3/c.640_645del (p.Glu214_Glu215del) in exon 9. After extensive information, parents decided to maintain female sex. Gonadal removal was performed and histological evaluation demonstrated deep fibrosis of testicular tissue. Follow-up till 8.5 years of age showed somatic and neuro-psychological development fitting with the female sex. CONCLUSIONS: Management of a child with the rare 17ß-HSD3 deficiency remains challenging. Any decision must be carefully evaluated with parents. Long-term follow-up must be warranted by a multidisciplinary DSD team to evaluate the adequacy of the choices made on quality of life in later life.