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Cited by 129Growth Hormone and Insulin-like Growth FactorsCardiovascular Health and Disease PreventionHormonal and reproductive studies

Endothelial dysfunction in hypopituitary adults with growth hormone deficiency

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M Evans, Davies, Goodfellow, Rees, Scanlon·1999·Clinical Endocrinology
DOI 10.1046/j.1365-2265.1999.00671.x
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Abstract

OBJECTIVES: Adult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age- and sex-matched controls. PATIENTS: Seventeen hypopituitary adults with GHD (13 male, 4 female) aged 26-54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age- and sex-matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction. MEASUREMENTS: Using an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium-dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium-independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF-1, and studied the relationship of these parameters to endothelial function. RESULTS: Flow mediated endothelium-dependent dilatation (FMD), expressed as a percentage change from resting base-line diameter, was significantly impaired in the GHD group (3.70 +/- 2.36% vs. 7.30 +/- 2.42%, P < 0.001). In contrast, GTN-mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 +/- 18.1 vs. 15.89 +/- 6.65 mU/l, P < 0.05) and glycated haemoglobin (HbA1c) levels (5.29 +/- 0.43 vs. 4.91 +/- 0.43%, P < 0.05) were significantly higher in the GHD group. FMD in both groups showed an inverse relationship with total cholesterol (r = -0.58, P < 0.05, GHD and r = -0.55, P < 0.05 controls). However, in the GHD subjects, there was a strong inverse relationship between FMD and LDL-cholesterol (r = -0.81, P < 0.0001). No other relationships were noted between FMD and any other metabolic parameters, or characteristics of GHD. CONCLUSIONS: Endothelial dysfunction is present in GH deficient adults prior to the onset of overt atherosclerotic disease. The similar glucose yet elevated fasting insulin levels imply a state of relative insulin insensitivity. The strong inverse correlation between endothelial dysfunction and LDL-cholesterol suggests a possible aetiological role for LDL-cholesterol in the pathogenesis of any excess cardiovascular risk associated with adult hypopituitarism.

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  • Altered body composition, insulin resistance, hypertension, unfavorable lipid profile, endothelial dysfunction and atherosclerosis have been found in several studies on patients with long-term GHD.

    “Altered body composition, insulin resistance, hypertension, unfavorable lipid profile, endothelial dysfunction and atherosclerosis have been found in several studies on patients with long-term GHD (74,76,77,(82)(83)(84)(85)(86)(87).”

    From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [82]

    The Discussion (p. 461) reports impaired endothelial function in GHD adults and discusses insulin resistance, altered body composition, and reports of unfavorable lipid profiles. But its own study found no quantitative lipid-profile difference; the Subjects section says all participants were normotensive, and the paper describes endothelial dysfunction as preceding overt atherosclerotic disease rather than finding atherosclerosis in them. Thus this source supports only part of the list. (LLM, conf=0.89)

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Research works printed but not linked: 6

  1. Bengtsson, B.A., Eden, S., Lonn, L., Kvist, H., Stockland, A., Lindstedt, G., Boseaus, I., Tolli, J., Sjostrom, L. & Isaksson, O. (1993) Treatment of adults with GHD with recombinant human GH. Journal of Clinical Endocrinology and Metabolism, 76: 309-317.
  2. Boger, R.H., Skamira, C., Bode-Buger, S.M., Brabant, G., von zur Muhlen, A. & Frolich, J.C. (1996) Nitric oxide may mediate the haemodynamic effects of recombinant human GH in patients with acquired GHD. Journal of Clinical Investigation, 98, 2706-2713.
  3. Bones, C., Bellamy, M., Brownlee, M., Goodfellow, J., Ramsey, M.W., Gorman, S.T. & Lewis, M.J. (1997) Endothelial function in healthy young adults is rapidly improved by physical training. European Heart Journal, 18, 265.
  4. Goodfellow, J., Ramsey, M., Bellamy, M., Gorman, S., Brownlee, M. & Lewis, M. (1998) Effect of dietary omega-3 fatty acids (fish oils) supplements on endothelial dysfunction in hypercholesterolaemic subjects. European Heart Journal, in press.
  5. Henderson, A. (1991) Endothelium in control. British Heart Journal, 65, 116-125.
  6. Streicher, R., Katzka, J., Muller, G., Wiedland, D., Siegmeister, G., Munk, M. & Krone, W. (1996) SERBP-mediates activation of LDL receptor promoter region by insulin and IGF-1. Journal of Biology and Chemistry, 271, 7128-7133.

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Authors
Evans, M., Davies, Goodfellow, Rees, & Scanlon
Affiliations
University Hospital of Wales (GB)
Corresponding author
M Evans
ORCID
M Evans
Venue
Clinical Endocrinology
Publisher
Wiley
Published
1999-04
Volume
50
Issue
4
Pages
457-464
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1046/j.1365-2265.1999.00671.x
OpenAlex
W1940926892
Cited by
129
References
49
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 3
FWCI
7.72
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 998 d)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
endothelial dysfunction, adult growth hormone deficiency, hypopituitarism, flow-mediated dilation, brachial artery, reactive hyperemia, nitroglycerin, insulin resistance, HbA1c, total cholesterol, insulin-like growth factor I, cardiovascular risk, atherosclerosis, hormone replacement therapy, lipid profile, endothelium-dependent vasodilatation, endothelium-independent vasodilatation
MeSH terms
Adult, Blood Glucose, Brachial Artery, Cardiovascular Diseases, Endothelium, Vascular, Female, Nitroglycerin, Humans, Hypopituitarism, Insulin, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Growth Hormone, Ultrasonography, Vasodilation, Case-Control Studies

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