Consequence of Lifetime Isolated Growth Hormone Deficiency

The primary goal of this proposal is to determine the consequences of life-long lack of GH on body composition, muscle strength, cardiovascular status, cardiovascular risk factors, thyroid status and bone density and metabolism, and to test which of these parameters are reversed by a 6-month course of GH replacement therapy. In addition, we want to test the hypothesis that heterozygosity for this GHRHR mutation causes a phenotype that may be intermediate between the one present in homozygous normal subjects and in homozygous affected GHD patients. This is relevant because inactivating mutations in the GHRHR are being described with increasing frequency in populations of different genetic background, suggesting that individuals with faulty single GHRHR alleles may be present in significant numbers in the general population.

Official Title

Consequence of Lifetime Isolated Growth Hormone Deficiency.

Conditions

•  Growth Hormone Deficiency

Study Type

Interventional

Study Design

Treatment, Non-Randomised, Open Label, Historical Control, Single Group Assignment, Efficacy Study.

Further Details

Primary Outcome Measures:

• Body composition
  [Time Frame: after 6 months of GH and after wash out (6 and 12 months)]
  [Designated as safety issue: No]
• Lipid levels
  [Time Frame: after 6 months of GH and after 6 and 12 months of wash out]
  [Designated as safety issue: No]
• Heart function
  [Time Frame: after 6 months of GH and after 6 and 12 months of wash out]
  [Designated as safety issue: No]

Specific AIM 1: To study anthropometric parameters, cardiovascular and metabolic status and cardiovascular risk profile, including inflammatory markers of cardiovascular relevance, muscle strength, bone density and bone metabolism, and thyroid status of twenty GH-naïve adult GHD subjects who are homozygous for a null GHRHR mutation and to compare them with twenty age- and sex- matched normal controls from the same population.

Specific AIM 2: To observe the changes in all the above parameters that occur in GHD subjects after a 6-months treatment with hGH replacement, and their reversibility after a 6-months washout period.

Specific AIM 3: To determine effect of heterozygosity for the GHRHR mutation. To this end, we propose to genotype a large number of apparently normal members of the Itabaianinha community with the goal of separating subjects homozygous for the wild-type allele from subjects heterozygous for the GHRHR mutation, and to compare their phenotype with the one observed in subjects homozygous for the wild type allele residing in the same geographical area.

Together, these studies will determine the effect of lifetime absence of GH on multiple organ functions and their response to hGH therapy, and will tell if heterozygosity for mutations in the GHRHR gene is associated with a detectable phenotype.

Study Start

September 2005

Eligibility & Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Genders Eligible for Study: Both
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Lifetime isolated and untreated growth hormone deficiency

Exclusion Criteria:

• Age below 18 years, pregnancy, diabetes

Total Enrolment

400

Contact Details

Roberto Salvatori, (Md)
410-955-3921
salvator@jhmi.edu

Location:

Federal University of Sergipe
Aracaju, Sergipe
Brazil, 49060