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

This study has been completed.
Sponsor:
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00825617
First received: January 20, 2009
Last updated: NA
Last verified: January 2009
History: No changes posted

January 20, 2009
January 20, 2009
October 1996
October 1999   (final data collection date for primary outcome measure)
quantitative liver function tests [ Time Frame: 1996-1999 ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
Not Provided
Not Provided
Not Provided
Not Provided
 
Quantitative Liver Functions in Turner Syndrome With and Without Hormone Replacement Therapy
Quantitative Liver Functions in Turner Syndrome With and Without Hormone Replacement Therapy

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.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Turner Syndrome
Drug: Hormone replacement therapy
Women with TS were treated with oral hormone substitution consisting of 2 mg 17β-estradiol/day for days 1-12, 2 mg 17β-estradiol/day and 1 mg norethisterone acetate/day for days 13-22 and 1 mg 17β-estradiol/day for days 23-28 (Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark)
Other Name: Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark
Experimental: HRT
Women with TS were treated with oral hormone substitution consisting of 2 mg 17β-estradiol/day for days 1-12, 2 mg 17β-estradiol/day and 1 mg norethisterone acetate/day for days 13-22 and 1 mg 17β-estradiol/day for days 23-28 (Trisekvens, Novo Nordisk A/S, Bagsværd, Denmark)
Intervention: Drug: Hormone replacement therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
June 2000
October 1999   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Turner syndrome by karyotype

Exclusion Criteria:

  • Thyroid abnormality
  • Glucocorticoid treatment
Female
Not Provided
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00825617
19963561
Yes
MD, PhD, DMSc Claus H. Gravholt, Medical department M, Aarhus University Hospital, Denmark
University of Aarhus
Not Provided
Principal Investigator: J S Christíansen, Professor Medical departmnet M, Aarhus University Hospital, NBG, Denamrk,
University of Aarhus
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP