X-Message-Number: 12128
Date: Tue, 13 Jul 1999 20:44:01 -0700 (PDT)
From: Doug Skrecky <>
Subject: GH deficiency promotes atherosclerosis

Citations: 1-3
<1>
Authors
  Pfeifer M.  Verhovec R.  Zizek B.  Prezelj J.  Poredos P.  Clayton RN.
Institution
  Department of Endocrinology, Diabetes and Metabolic Diseases, University
  Medical Center, Ljubljana, Slovenia.
Title
  Growth hormone (GH) treatment reverses
  early atherosclerotic changes in GH-deficient adults.
Source
  Journal of Clinical Endocrinology & Metabolism.  84(2):453-7, 1999 Feb.
Abstract
  Hypopituitary patients have increased mortality from vascular disease, and in
  these patients, early markers of atherosclerosis [increased
  carotid artery intima-media thickness (IMT) and reduced distensibility] are
  more prevalent. As GH replacement can reverse some risk factors of
  atherosclerosis, the present study examined the effect of GH
  treatment on morphological and functional changes in the carotid and brachial
  arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr
  old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18
  months. IMT of the common carotid artery (CCA) and the carotid bifurcation
  (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial
  artery were measured by B mode ultrasound before and at 3, 6, 12, and 18
  months of treatment, and values were compared with those in 12 age-matched
  control men. Serum concentrations of lipids, lipoprotein(a), insulin-like
  growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3)
  were also measured. In GHD men before treatment the IMTs of the CCA
  [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater
  (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm,
  respectively]. GH treatment normalized the IMT of the CCA by 6 months
  [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of
  the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r
  = -0.53; P < 0.0001). There was a significant improvement in flow-mediated
  EDD of the brachial artery at 3 months, which was sustained at 6 and 18
  months of GH treatment (P < 0.05). GH treatment increased high density
  lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low
  density lipoprotein cholesterol and was without effect on lipoprotein(a).
  There was no correlation between plasma lipids and changes in IMT or EDD of
  the arteries examined. In conclusion, GH treatment of hypopituitary GHD men
  reverses early morphological and functional atherosclerotic changes in major
  arteries and, if maintained, may reduce vascular morbidity and mortality. GH
  seems to act via IGF-I, which is known to have important effects on
  endothelial cell function.

<2>
Authors
  Marek J.  Kvasnicka J.  Weiss V.  Markova M.  Hass T.
Institution
  III. interni klinika 1. LF UK a VFN, Praha.
Title
  [Can normalization of vascular cytoadhesive activity be explained by the
  anti-atherosclerosis effect of growth
  hormone?]. [Czech]
Source
  Casopis Lekaru Ceskych.  137(22):690-3, 1998 Nov 16.
Abstract
  BACKGROUND: The increased mortality caused by premature
  atherosclerosis has been shown among patients with
  hypopituitarism receiving conventional hormone treatment but
  with unsubstituted growth hormone
  deficiency. This experience belongs among the most important arguments in
  favour of replacement with growth hormone.
  The mechanisms of the antiatherogenic effect of growth
  hormone are poorly understood. The protective effect of
  growth hormone on the vascular endothel and
  its intervention in the clotting process, which have not been yet elucidated,
  may be the causative factors. METHODS AND RESULTS: The endothelial damage as
  given by measuring of circulating soluble cytoadhesive molecules sE-selectin,
  sP-selectin and intercellular adhesive molecule 1 (ICAM 1) was measured in 15
  adult panhypopituitaric patients before and after 1 year treatment with
  recombinant human growth hormone. The blood
  levels of all of these cytoadhesive molecules decreased significantly (p <
  0.01) during the treatment. None of the concomitantly followed coagulation
  tests (prothrombin time, activated partial thromboplastin time, fibrinogen,
  antithrombin III, von Willebrand's factor and D-dimer) was significantly
  changed during the treatment. The tendency to decrease (p = 0.054) was
  observed with antithrombin III. CONCLUSIONS: The decrease of circulating
  cytoadhesive molecules in blood during the treatment of
  growth hormone gives evidence for its
  protective effect, either direct or mediated, on the vascular endothel. These
  findings could bring an explantation for the premature atherosclerotic
  changes in hypopituitarism and antiatherogenic effect of
  growth hormone.

<3>
Authors
  Hassan HM.  Kohno H.  Kuromaru R.  Honda S.  Ueda K.
Institution
  Department of Paediatrics, Kyushu University, Faculty of Medicine, Japan.
Title
  Body composition, atherogenic risk factors and apolipoproteins following
  growth hormone treatment.
Source
  Acta Paediatrica.  85(8):899-901, 1996 Aug.
Abstract
  We studied the change in atherogenic risk factors in 27 children, 21 boys and
  6 girls, 6 to 14 years of age, with growth
  hormone deficiency during 12 months of
  growth hormone replacement therapy. Changes
  in body composition and lipid profile during growth
  hormone treatment were evaluated. The atherogenic index was
  calculated using the equation [(total cholesterol- high-density lipoprotein
  cholesterol)(apolipoprotein B)]/[(apolipoprotein AI)(high-density lipoprotein
  cholesterol)]. Body fat decreased (p < 0.01), associated with an increase in
  lean body mass (p < 0.01). Total cholesterol and high-density lipoprotein
  cholesterol showed no significant changes. The atherogenic index
  significantly decreased from 1.44 +/- 0.60 to 1.09 +/- 0.52 (p < 0.01) after
  12 months. Apolipoproteins CII and CIII increased throughout the study period
  (p < 0.01). Lipoprotein(a) and apolipoproteins AI, B and B/AI ratio did not
  change significantly. In conclusion, growth
  hormone treatment improved body composition and reduced
  atherogenic risk factors in children with growth
  hormone deficiency.

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