Body mass index and blood glucose: correlations with serum insulin, growth hormone, and insulin-like growth factor-1 levels in patients with diffuse idiopathic skeletal hyperostosis (DISH).

Obesity is a frequent co-morbid condition associated with diffuse idiopathic skeletal hyperostosis (DISH). Serum growth hormone (GH), insulin-like growth factor (IGF-1) and insulin are significantly elevated in patients with DISH. In this study, we examined the relationship between body mass index (BMI) and basal serum GH, IGF-1, and insulin concentration in a group of 36 DISH patients. Basal serum insulin levels were significantly elevated (P<0.001) in DISH patients with a BMI>28 kg m(-2), classified as obese, compared with DISH patients with BMI ranging from 23 to 28 kg m(-2). In addition, BMI strongly positively correlated with serum insulin concentration in DISH patients (adjusted r2 = 0.348, P<0.001). However, BMI did not correlate with either basal serum GH (adjusted r2 = -0.013) or IGF-1 levels (adjusted r2 = -0.010) in DISH. We conclude that BMI does not seem to contribute to elevated serum GH and IGF-1 levels in symptomatic DISH.

Role of the growth hormone/insulin-like growth factor-1 paracrine axis in rheumatic diseases.

OBJECTIVES: Hypothalamic-pituitary axis abnormalities have been associated with systemic disturbances in several rheumatic diseases. Longitudinal analysis of erythrocyte, serum, urinary and synovial fluid growth hormone (GH), insulin-like growth factor-1 (IGF-1), and somatostatin levels could provide important surrogate measures of disease activity in rheumatic diseases. METHODS: The authors reviewed the population and longitudinal studies literature on GH, IGF-1, and somatostatin levels in rheumatic disorders using the PubMed and Medlines databases from the National Library of Medicine. In addition to the literature search, primary data were analyzed for basal somatostatin levels in patients with hand, knee, and spine osteoarthritis (OA) as well as primary and secondary hip OA. RESULTS: A review of the literature supports the view that hypothalamic-pituitary axis dysfunction accompanies clinical symptoms in many rheumatic diseases. In studies from our laboratory, serum GH levels were elevated in patients with OA, rheumatoid arthritis (RA), fibromyalgia, and diffuse idiopathic skeletal hyperostosis but not in patients with gout, pseudogout, or systemic lupus erythematosus. In OA and RA, synovial fluid GH levels exceeded serum GH levels. However, the literature remains controversial regarding the significance of changes in IGF-1 levels in rheumatic disorders. Many studies support an inverse relationship between age and IGF-1. Elevated serum GH levels in various rheumatic diseases were not coupled to changes in serum IGF-1 in diffuse idiopathic skeletal hyperostosis, RA, and fibromyalgia. In particular, serum IGF-1 levels in OA were shown to be lower or no different compared with age-matched normal subjects. Further, in OA, impaired articular chondrocyte response to IGF-1 was attributed, in part, to low synovial fluid IGF-1 that further compromised IGF-1 chondrocyte responses as a result of increased levels of synovial fluid IGF-1 binding proteins. Of note, serum somatostatin levels and "specific" somatostatin receptor levels were often lower in RA and systemic lupus erythematosus, but basal serum somatostatin levels were generally not altered in OA. CONCLUSIONS: The results of these analyses support the view that some rheumatic diseases such as OA and diffuse idiopathic skeletal hyperostosis, heretofore considered to be purely focal and degenerative, could be reclassified as systemic metabolic disturbances. We propose that serum GH, IGF-1, and somatostatin levels be monitored on a longitudinal basis during the course of medical therapy of rheumatic diseases to determine the extent to which changes in clinical symptoms (exemplified by reduced pain and inflammation and improved range of joint motion) are accompanied by changes in the basal concentration of these hypothalamic/pituitary-related hormones.

Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome.

Standard radioimmunoassay (RIA) was employed to quantify basal serum growth hormone (GH), insulin-like growth factor-I (IGF-1), and insulin levels in 32 normoglycemic patients with clinically active fibromyalgia and in 29 normoglycemic control subjects. The GH concentration was significantly higher (P < 0.001) in female fibromyalgia patients than age-matched, normal female subjects. In contrast, basal serum IGF-1 concentrations did not differ between these groups. A scatter plot generated from two-stage, least-squares analysis showed that serum GH lacked correlation with the serum IGF-1 concentrations of normal female subjects (P = 0.73) and female fibromyalgia patients (P = 0.19). In addition to the results from serum GH and IGF-1 RIA, we also found significantly higher fasting serum insulin levels (P = 0.03) in male fibromyalgia patients and a trend toward elevated fasting serum insulin levels in the female fibromyalgia population ( P = 0.07), with the mean fasting level in the male fibromyalgia group (35.7 microU/ml(-1)) exceeding the upper limit of normal serum insulin levels (i.e., 27 microU/ml(-1)). Based on these results, basal serum GH and fasting serum insulin levels appear to be valuable surrogate markers in clinically active, normoglycemic fibromyalgia patients.

Age-related changes in serum growth hormone, insulin-like growth factor-1 and somatostatin in system lupus erythematosus.

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.

The serum growth hormone to somatostatin ratio is skewed upward in rheumatoid arthritis patients.

Basal serum growth hormone, insulin-like growth factor-1 (IGF-1) and somatostatin concentration were measured by standard radioimmunoassay in patients with a diagnosis of rheumatoid arthritis (RA) according to the criteria of the American College of Rheumatology as well as in a group of age-matched normal subjects. RA patients exhibited significantly elevated (age, 45-55 yrs, p less than 0.05; 55 yrs and older, p less than 0.01) serum growth hormone levels compared to age-matched individuals from the control group. IGF-1 was unchanged. Serum somatostatin levels were reduced in RA patients between 45 and 55 yrs but reached a significant reduction (p less than 0.0001) in RA patients, 55 years and older compared to age-matched individuals from the control group. RA patients treated with prednisone did not exhibit changes in either growth hormone or IGF-1 levels compared to RA patients treated principally with non-steroidal anti-inflammatory drugs and methotrexate. These results indicated that symptomatic RA is associated with elevated serum growth hormone without concomitant changes in IGF-1 compared to individuals from the control group. Reduced somatostatin levels in older RA patients resulted in a skewed upward growth hormone to somatostatin ratio. We conclude that the serum growth hormone to somatostatin ratio may be a useful surrogate marker of disease activity in symptomatic RA.

Intra-erythrocyte deposition of growth hormone in rheumatic diseases.

Standard radioimmunoassay was employed to quantify matched basal intra-erythrocyte growth hormone (GH) and serum GH levels from patients with osteoarthritis, diffuse idiopathic skeletal hyperostosis (DISH), gout, and Sjögren's syndrome and in a group of normal volunteers (control group). Basal intra-erythrocyte GH concentration was significantly higher ( P<0.05) than serum GH concentration in blood samples from patients with osteoarthritis and DISH but not from those with gout or Sjögren's syndrome. Regression analysis determined that basal serum GH levels did not correlate with age. While intra-erythrocyte GH levels exceeded serum GH levels in osteoarthritis and DISH, intra-erythrocyte GH was not a strong predictor of serum GH levels in osteoarthritis, DISH, or in the control group.

Growth hormone and insulin-like growth factor-I in symptomatic and asymptomatic patients with diffuse idiopathic skeletal hyperostosis (DISH).

Basal serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentration was measured by radioimmunoassay in patients with diffuse idiopathic skeletal hyperostosis (DISH) with muscle and joint pain and stiffness (symptomatic group) and in DISH patients without these constitutional clinical symptoms (asymptomatic group), but with persistent radiographic evidence of DISH. Serum GH and IGF-I was also measured in normal volunteers (control group) matched for gender and age to patients with DISH. Symptomatic male and female DISH patients had elevated serum GH and IGF-I concentration when compared to the control group. Asymptomatic DISH patients had serum GH levels that were significantly lower than their symptomatic counterparts. Clinical improvement did not alter serum IGF-I concentration. We conclude that serum GH concentration could be employed to monitor clinical remission in DISH.