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The diagnostic approach to acromegaly and GH deficiency frequently includes measurement of several components of the insulinlike growth factor (IGF) system. IGF-I levels are reported to be good predictors of active and cured acromegaly, but are commonly found within the normal age-adjusted range in adult GH-deficient (GHD) patients. Circulating concentrations of IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and free IGF-I reflect the GH secretory status, but their diagnostic accuracy is still debated. In this study serum levels of total and free IGF-I, IGFBP-3, ALS, and IGFBP3-IGF-I and IGFBP-3-ALS complexes were determined in patients previously diagnosed with active (n 5 67) or inactive (n 5 16) acromegaly and adult GHD (n 5 34) and compared with results obtained in 58 healthy controls. In healthy subjects, IGF-I, IGFBP-3, ALS, and both IGFBP-3 complexes declined with age; a correlation was found between IGF-I and IGFBP-3 (r 5 0.59; P , 0.001), ALS (r 5 0.67; P , 0.001), and free IGF-I (r 5 0.40; P , 0.05). Active acromegalic patients showed a significant increase in all parameters tested. IGF-I concentrations were above 12 SD in 100% of patients, whereas slightly lower sensitivities were shown for IGFBP-3 (85%), ALS (88%), and free IGF-I (94%). In this group, IGF-I exhibited a slightly higher correlation with IGFBP-3 (r 5 0.83; P , 0.001) than with ALS levels (r 5 0.78; P , 0.001). In cured acromegalic patients, we observed the normalization of all parameters but free IGF-I levels. Adult GHD patients showed a significant reduction of all hormones. Unlike active acromegalic patients, all parameters had only a modest sensitivity in GHD; suppression below ‐2 SD was observed in 41% of GHD patients for IGF-I, 47% for IGFBP-3, 32% for ALS, and 35% for free IGF-I measurements. Previous radiotherapy and GH peak response below 3 mg/L were associated with significantly lower IGF-I, IGFBP-3, and ALS levels. IGF-I levels were significantly correlated to ALS (r 5 0.68; P , 0.001) and IGFBP-3 (r 5 0.64; P , 0.001) as well as with free IGF-I (r 5 0.67; P , 0.001) levels. By multiple regression analysis, the number of anterior pituitary hormones impaired was the most predictive indicator of IGF-I, IGFBP-3, and free IGF-I levels in GHD patients; conversely, the GH peak response better anticipated ALS concentrations. The pattern of IGFBP-3 complexes paralleled previous hormonal findings. In active acromegalic patients, IGFBP-3-IGF-I levels were 5.4-fold higher than in controls and were above 12 SD in 95% of patients, whereas IGFBP-3-ALS levels were elevated in 15% of cases. On the other hand, both IGFBP-3 complexes were able to predict GHD in only a minority of cases. Taken together, these data support the diagnostic role of IGF-I in acromegaly and suggest that free IGF-I and the IGFBP-3-IGF-I complex can assist diagnostic strategies in this condition. All markers are of limited predictive value in adult GHD, as hormonal values are commonly found within the normal limits. In these patients, low IGFBP-3 and IGF-I concentrations can add further clinical information on the residual GH activity. (J Clin Endocrinol Metab 86: 3001‐ 3008, 2001)

Insulin‐like growth factors (IGFs) and IGF binding proteins (IGFBPs) play an important role in cell growth and differentiation. Clinical and epidemiological studies have indicated that measuring IGFs and IGFBPs in blood has potential implications in assessing growth‐related abnormalities and risks of certain types of cancer. To facilitate the application, we reported a large collection of reference ranges of IGFs and IGFBPs in normal population and evaluations of these molecules in serum and plasma as well as the impact of freeze‐thaw cycles on the measurement. IGF‐I, IGFBP‐3 and ALS showed a similar pattern of change associated with age. Levels of these molecules were low at birth and increased with age through puberty. After puberty the levels declined slowly with age. Overall, IGF‐I, IGFBP‐3 and ALS were slightly higher in females than in males. Free IGF‐I accounted for about 1% of the total IGF‐I and its variation with age was similar to total IGF‐I. IGF‐II levels were also increased with age from birth to puberty, but became stable after puberty. There was little difference in IGF‐II levels between genders. IGFBP‐2 levels declined with age from birth to puberty. Levels of IGFBP‐6 in contrast were increased with age. These IGF binding proteins were higher in males than in females. IGFs, IGFBP‐3 and ALS were 5‐10% higher in serum than in plasma. IGFBP‐2 and IGFBP‐6 differed substantially between serum and plasma. Freeze‐thaw treatment up to five cycles had little impact on plasma levels of IGFs and IGFBP‐3. Our observations suggest that levels of IGFs and their binding proteins are varied with age, gender, and types of specimen and that these variations need to be taken into consideration when IGFs and their binding proteins are utilized in clinic and research. J. Clin. Lab. Anal. 13:166–172, 1999. © 1999 Wiley‐Liss, Inc.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating condition that frequently causes death or significant disabilities. Blood tests to predict possible early complications could be very useful aids for therapy. The aim of this study was to analyze serum levels of kallikrein 6 (KLK6) in individuals with aSAH to determine the relevance of this protease with the outcome of these patients. Methodology/Principal Findings: A reference interval for KLK6 was established by using serum samples (n = 136) from an adult population. Additionally, serum samples (n = 326) from patients with aSAH (n = 13) were collected for 5 to 14 days, to study the concentration of KLK6 in this disease. The correlation between KLK6 and S100B, an existing brain damage biomarker, was analyzed in 8 of 13 patients. The reference interval for KLK6 was established to be 1.04 to 3.93 ng/mL. The mean levels in patients with aSAH within the first 56 hours ranged from 0.27 to 1.44 ng/mL, with lowest levels found in patients with worse outcome. There were significant differences between patients with good recovery or moderate disability (n = 8) and patients with severe disability or death (n = 5) (mean values of 1.03 ng/mL versus 0.47 ng/mL, respectively) (p,0.01). There was no significant correlation between KLK6 and S100B. Conclusions/Significance: Decreased serum concentrations of KLK6 are found in patients with aSAH, with the lowest levels in patients who died.