Lupus Disease

Age-related Changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in Systemic Lupus Erythematosus

Charles W Denko¹ and Charles J Malemud^{2      1}Department of Medicine/Division of Rheumatic Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106-5076 USA, ²Department of Medicine/Division of Rheumatic Diseases, and Department of Anatomy, Case Western Reserve University School of Medicine, Cleveland, Ohio, 44106-5076 USA, BMC Musculoskeletal Disorders 2004, 5:37doi:10.1186/1471-2474-5-37
© 2004 Denko and Malemud; licensee BioMed Central Ltd.  This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects.

Methods

Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay.

Results

Serum growth hormone levels failed to correlate with age (r² = 3.03) in the entire group of normal subjects (i.e. 20 – 80 years). In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r² = 0.092). Of note, serum growth hormone was positively correlated with age (adjusted r² = 0.269) in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p < 0.001) in systemic lupus erythematosus patients, but only when compared to the entire group of normal subjects. Serum somatostatin levels differed from normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus patients.

Conclusions

These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome where significantly higher serum growth hormone levels were found. Somatostatin levels in elderly systemic lupus erythematosus patients may provide a clinical marker of disease activity in these patients.

It is recommended that Transfer Factor Advanced formula to be used in autoimmune conditions.  Transfer Factor Plus is generally preferred for conditions caused by infection. Transfer Factors suppress over acting immune system to ease autoimmune conditions.  

Background

Systemic lupus erythematosus (SLE) is the protean autoimmune disorder with strong familial penetrance. Immunologically, Systemic Lupus Erythematosus is characterized by aberrations in T cell and B cell function [1,2], over-production of autoantibodies directed principally against nuclear antigens [3] as well as other tissue antigens, and deficiencies in the complement system [4]. Systemic Lupus Erythematosus is predominantly a disease of young females with peak incidence occurring between 20 and 40 yrs with a female to male ratio of 6–10:1 [5]. Although many of the principal pathophysiological changes associated with Systemic Lupus Erythematosus indicate organ involvement consistent with vascular inflammation and immune complex deposition [6], several prominent Systemic Lupus Erythematosus-related pathologic findings suggest systemic disturbances consistent with metabolic abnormalities [7]. However, surrogate blood or serum markers of systemic dysfunction such as erythyrocyte sedimentation rate and C-reactive protein levels, although frequently elevated in Systemic Lupus Erythematosus compared to normal subjects are often uninformative and unreliable as surrogate markers of Systemic Lupus Erythematosus disease activity [7].

We have shown that diverse rheumatic and musculoskeletal disorders, including osteoarthritis (OA) [8-12], diffuse idiopathic skeletal hyperostosis (DISH) [12,13] and hypermobility syndrome [14] as well as fibromyalgia [15] were characterized, in part, by elevated serum growth hormone levels. Growth hormone was also found sequestered in erythrocytes in OA and DISH patients at levels that significantly exceeded serum growth hormone levels [16] suggesting a putative mechanism by which "toxic" levels of growth hormone could be confined, or in cases of vascular inflammation, transported to joint synovial fluid or peripheral end-organs [11,16]. Further, medical therapy of OA and DISH principally with non-steroidal anti-inflammatory drugs (NSAIDs) which resulted in pain suppression and reduced stiffness as well as improved range of motion correlated with lower serum growth hormone levels consistent with levels found in normal subjects [10,13]. More recently, we showed that symptomatic rheumatoid arthritis (RA) patients were also characterized by elevated serum growth hormone levels [17], but treatment of RA with prednisone failed to significantly lower serum growth hormone levels.

Insulin-like growth factor-1 (IGF-1) synthesis is coupled to growth hormone via its capacity to stimulate hepatocyte IGF-1 production [11]. In several rheumatic and musculoskeletal disorders, elevated serum growth hormone was correlated with elevated IGF-1 levels [9,11,13,14] with osteoarthritis (OA) [8-10,12] and rheumatoid arthritis [17] (RA) being notable exceptions. In the case of OA, IGF-1 levels are significantly lower compared to normal control subjects [8-10,12]. However, medical therapy of OA principally with NSAIDs resulted in growth hormone and IGF-1 levels approaching normal [10] whereas in DISH patients treated with NSAIDs, reduced serum growth hormone levels failed to result in concomitant changes in IGF-1 [13].

Somatostatin is a 14 amino acid polypeptide whose principal function is to regulate growth hormone release from the pituitary [18]. Elevated serum and synovial fluid somatostatin levels have been associated with inflammatory responses [19] most notably in rheumatoid arthritis (RA) [20]. A recent study showed that patients with symptomatic RA were, in part, characterized by a skewed upward serum growth hormone to somatostatin ratio [17].

The present study was performed to determine the extent to which serum growth hormone, IGF-1 and somatostatin levels were modulated in patients with Systemic Lupus Erythematosus. A linear regression analysis was performed to determine the relationship between age and serum growth hormone and IGF-1 levels in a group of normal female subjects so that these values could be employed for comparison to a group of predominantly young, female SLE patients.

It is recommended that Transfer Factor Advanced formula to be used in autoimmune conditions.  Transfer Factor Plus is generally preferred for conditions caused by infection. Transfer Factors suppress over acting immune system to ease autoimmune conditions.  

Methods

All studies were performed at University Hospitals of Cleveland (UHC) and the Wade Park Veterans Administration Medical Center (VAMC), Cleveland, Ohio. The UHC and VAMC Institutional Review Boards approved the study design with the research protocol, which included informed consent, being in keeping with the Declaration of Helsinki. Normal subjects and Systemic Lupus Erythematosus patients were all volunteers. Systemic Lupus Erythematosus Patients met the clinical and laboratory criteria for the diagnosis of Systemic Lupus Erythematosus according to previously published classifications [21]. Patients with co-morbid conditions such as diabetes mellitus or hyperglycemia were excluded from the normal subject group as was any normal individual with evidence for rheumatic disorders in family members. This information was obtained by questioning potential normal subjects.

Blood drawn by venipuncture was clotted at room temperature, centrifuged, serum aliquots separated and stored at -70°C until assayed. Blood samples were generally collected during an identical 3–4 hr morning period to normalize the potential contribution of growth hormone pulses and serum glucose levels to serum growth hormone determinations [8-10]. Serum samples were included for serum growth hormone, IGF-1 or somatostatin determinations only if glucose levels measured by the highly sensitive hexokinase assay [8-10] were between 65 and 135 mg/dl attained either by overnight fasting or a fast of at least 4 hours or more. Insulin levels were measured as previously described [8-10]. An insulin level in the range of 5–27 μU/ml was considered normal.

Basal serum growth hormone and IGF-1 levels were determined by standard radioimmunoassay (RIA) (INCSTAR, Stillwater, MN) as previously described [8-10]. The lower limit of detection for serum growth hormone by the RIA was 0.4 ng/ml [8-10]. Serum growth hormone levels in samples falling at or below the lower limit of detection were excluded from the statistical analysis. Basal somatostatin levels in serum of 112 normal subjects and 55 Systemic Lupus Erythematosus patients stratified by age (i.e. <45, between 45 and 55 yrs and >55 yrs of age) were separately measured by RIA [17].

The 2-tailed T-test was employed to analyze the differences in means of serum growth hormone, IGF-1 and somatostatin concentrations in groups of unequal size where p < 0.05 was significant. The population sample size was sufficient to detect a 20% difference in serum growth hormone and IGF-1 levels between control subjects and Systemic Lupus Erythematosus patients and a 15% difference in serum somatostatin levels.

The relationship between serum growth hormone and IGF-1 levels as a function of age was analyzed from scatter plots by linear regression analysis employing SPSS 11.1 (SPSS, Inc., Chicago, IL) and SigmaPlot 8.0 (SPSS, Inc.) to calculate the adjusted r²-value and regression line, respectively.

Results of Systemic Lupus Erythematosus Study

It is recommended that Transfer Factor Advanced formula to be used in autoimmune conditions.  Transfer Factor Plus is generally preferred for conditions caused by infection. Transfer Factors suppress over acting immune system to ease autoimmune conditions.  

Immune System & Diseases

Transfer Factor & Immune Function that affect Cancer

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