Quantitative Liver Functions in Turner Syndrome With and Without Hormone Replacement Therapy

Turner Syndrome Clinical Trial

Official title:

Quantitative Liver Functions in Turner Syndrome With and Without Hormone Replacement Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00825617
• Other study ID #: 19963561
• Status: Completed
• Phase: N/A
• First received: January 20, 2009
• Last updated: January 20, 2009
• Start date: October 1996
• Est. completion date: June 2000

Study information

• Verified date: January 2009
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Several studies have demonstrated that Turner Syndrome patients have elevated liver enzymes readily suppressible by a short course of HRT. We wanted to estimated quantitative liver functions in a young group of Turner syndrome patients compared to a healthy control group.

Description:

Turner syndrome is due to the absence of a part of or the entire X chromosome in females. Stature is short, and morbidity is increased due to risk of osteoporosis and fractures, type 2 diabetes, ischemic heart disease, hypertension, and stroke, but also the risk of cirrhosis is increased. Clinical studies have shown a frequent occurrence of elevated liver enzymes, primarily alanine aminotransferase, g-glutamyl-transferase, and alkaline phosphatase, while bilirubin is normal.

We and others have shown a normalizing effect of hormone replacement therapy (HRT), containing 17bestradiol and a gestagen, on liver enzymes, which may point towards a protective effect on hepatocyte integrity. Marked architectural changes, including nodular regenerative hyperplasia, multiple focal nodular hyperplasia and cirrhosis are observed in some patients and are associated with a risk of liver-related complications. These changes are frequently associated with vascular disorders such as obliterative portal venopathy, probably related to congenitally abnormal vessels. Steatosis, steatofibrosis, and steatohepatitis are seen and may be caused by metabolic disorders. In addition, bile duct alterations resembling small duct sclerosing cholangitis are observed in several patients. Presently, it is not known whether these perturbations in liver morphology and in liver-derived enzymes are related to functional defects in females with TS and whether this may change by HRT. To further explore quantitative liver function in TS, we examined adult women with TS on and off HRT and compared them with a control group of age matched normal women. We used the galactose elimination capacity to assess hepatocyte cytosol activity, the plasma clearance of indocyanine green to assess hepatic blood flow and excretory liver cell function independently of hepatic blood flow, the antipyrine plasma clearance to estimate hepatic microsomal system activity, and the functional hepatic nitrogen clearance to assess mitochondrial- cytosolic metabolic capacity for conversion of amino-nitrogen.We assumed that one or more these metabolic liver functions would be diminished in untreated TS and normalized by HRT. Our principal objective was to understand mechanistically how HRT improves liver function in TS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2000
• Est. primary completion date: October 1999
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Turner syndrome by karyotype

Exclusion Criteria:

• Thyroid abnormality

• Glucocorticoid treatment

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gonadal Dysgenesis
• Primary Ovarian Insufficiency
• Syndrome
• Turner Syndrome

Intervention

Drug:
• Hormone replacement therapy
Women with TS were treated with oral hormone substitution consisting of 2 mg 17ß-estradiol/day for days 1-12, 2 mg 17ß-estradiol/day and 1 mg norethisterone acetate/day for days 13-22 and 1 mg 17ß-estradiol/day for days 23-28 (Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark)

Locations

Country	Name	City	State
Denmark	Medical department M and Investigational Laboratories	Aarhus C	Jutland

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	quantitative liver function tests		1996-1999	No