Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practice.

BACKGROUND: There is increasing reliance on consensus criteria for decision making. Recent criteria state that acromegaly is excluded by a nadir GH during an oral glucose tolerance test (OGTT) of < 1 microg/l and a normal level of IGF-I. OBJECTIVE: To study GH and IGF-I assay performance close to cut-off values for active acromegaly. DESIGN AND METHODS: Two serum samples known to give borderline results were sent to all centres participating in the UK National External Quality Assessment Service (NEQAS). Sample A was assigned to be a nadir during an OGTT and sent for GH assessment to 104 centres. Sample B, with a clinical scenario, was sent to 23 centres that measure IGF-I, and these centres were asked to measure IGF-I, interpret the result and provide the source of their reference ranges (RRs). RESULTS: For sample A, the median GH was 2.6 mU/l (range 1.04-3.5 mU/l). Applying a conversion factor (CF) of 2.0 (1 microg/l = 2 mU/l), the most negatively biased method classified 10% of the values consistent with acromegaly, while the most positively biased method classified all values as consistent with the diagnosis. Applying a CF of 3.0 (1 microg/l = 3 mU/l), only 11% of results were consistent with acromegaly. For sample B, the median IGF-I was 50.8 nmol/l (range 24.3-60.9 nmol/l). All centres used age-related RRs. There was a 50% variation in the upper limit of the RRs between centres. Overall, 30% of the IGF-I results were against the diagnosis. There was little agreement in the RRs quoted by centres using the same method. CONCLUSION: Variability in assay performance, coupled with use of inappropriate CFs and RRs, undermines the applicability of international consensus criteria to local practice.

Low-dose GH replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome.

OBJECTIVE: Adult growth hormone deficiency (AGHD) is associated with an adverse lipid profile. The majority of previous studies of GH replacement have used supraphysiological doses and reported favourable changes in the lipid profile. Whether this beneficial effect is the result of pharmacological GH therapy, or occurs in response to low-dose GH replacement aimed at normalization of the serum IGF-I, has not been fully elucidated. STUDY DESIGN: We studied 67 patients with GH deficiency using a low-dose individualized GH replacement regimen. GH was commenced at a dose of 0.27 mg/day and the GH dose titrated until the serum IGF-I was normalized. Serum lipids were assessed at baseline, 12 and 24 months. RESULTS: A reduction in total cholesterol (TC) was observed at 12 (6.01 vs. 5.77 mmol, P = 0.04) and 24 months (6.01 vs. 5.56, P = 0.09). The reduction in LDLC failed to reach significance at 12 months (3.97 vs. 3.8, P = 0.09), but was significant at 24 months (3.97 vs. 3.50, P = 0.02). Levels of HDLC did not change significantly at 12 or 24 months. Significant improvements in the TC/HDLC ratio were observed at both 12 (5.68 vs. 5.29, P = 0.01) and 24 months (5.68 vs. 4.86, P = 0.007). A significant fall in triglycerides (TG) was present at 12 months (2.07 vs. 1.83, P = 0.01), and was maintained at 24 months, but was no longer significant (2.07 vs. 1.89, P = 0.28). At 12 months there was no correlation between improvements in lipid parameters and either the change in IGF-I SD score or the GH dose. Using multivariate analysis the change in TC, LDLC and the TC/HDLC ratio with 12 months GH replacement were determined by the baseline TC, LDLC and TC/HDLC levels (R2 = 0.18, P = 0.004; R2 = 0.20, P = 0.006; and R2 = 0.33, P < 0.0001), respectively. CONCLUSIONS: Low-dose individualized GH replacement aimed at normalization of the serum IGF-I is associated with significant improvements in TC, LDLC, TGs and the TC/HDLC ratio. The greatest improvements are observed in patients with the most adverse lipid profiles at baseline. Improvements are independent of changes in the IGF-I SDS and GH dose.

A comparison of three procedures for the detection of Bence-Jones proteinuria.

A traditional electrophoretic procedure for detection of Bence-Jones proteinuria, employing Amido black stain on 200-fold concentrated urine, has been compared to two procedures employing highly sensitive protein stains not requiring prior urine concentration. All three procedures were carried out on 80 random urine samples screened for Bence-Jones proteinuria and 10 samples were provided by patients attending a myeloma clinic. A new procedure employing modified Coomassie brilliant blue stain on unconcentrated urine showed comparable sensitivity to the established procedure (82% versus 88%, respectively) and specificity (77% versus 74%, respectively), when assessed against immunofixation as a reference method. However, the new method is considerably quicker and cheaper. A second method, employing Gold stain, showed enhanced sensitivity (94% versus 88% for Amido black) but lower specificity (62% versus 74% for Amido black). However, this method is labour intensive and relatively expensive. Our data suggest that the procedure employing modified Coomassie brilliant blue may be a suitable alternative to the traditional procedure commonly used in many clinical laboratories.

Apolipoprotein E genotypes and serum lipid levels in Alzheimer's disease and multi-infarct dementia.

OBJECTIVE: Assessment of apolipoprotein E genotype, serum cholesterol, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol levels in different types of dementia. SUBJECTS: 102 consecutive referrals to an old age psychiatry service based at Manchester were classified according to clinical criteria based on ICD 10. RESULTS: Thirty-seven were considered to have Alzheimer's disease, 16 multi-infarct dementia and 33 to be free from dementia. Sixteen patients, in whom a definitive diagnosis could not be reached or sufficient information was not available, were excluded from the study. There was an increase in the prevalence of the Apo E4 allele in both Alzheimer's disease (chi 2 = 3.82, p < 0.05) and multi-infarct dementia (chi 2 = 1.93, p < 0. = 0.16) by Wald tests compared to individuals without dementia. The increased prevalence of the E4 Allele in multi-infarct dementia was not related to serum lipid levels. CONCLUSION: The hypothesis that the onset of multi-infarct dementia may be precipitated by E4's mediation of higher serum cholesterol levels is not supported by the present study.