The European Federation of Clinical Chemistry and Laboratory Medicine syllabus for postgraduate education and training for Specialists in Laboratory Medicine: version 5 - 2018.

Although laboratory medicine practise varies across the European Union's (EU) member states, the extent of overlap in scope is such that a common syllabus describing the education and training associated with high-quality, specialist practise can be identified. In turn, such a syllabus can help define the common set of skills, knowledge and competence in a Common Training Framework (CTF) for non-medical Specialists in Laboratory Medicine under EU Directive 2013/55/EU (The recognition of Professional Qualifications). In meeting the requirements of the directive's CTF patient safety is particularly enhanced when specialists seek to capitalise on opportunities for free professional migration across EU borders. In updating the fourth syllabus, the fifth expands on individual discipline requirements, new analytical techniques and use of statistics. An outline structure for a training programme is proposed together with expected responsibilities of trainees and trainers; reference is provided to a trainee's log book. In updating the syllabus, it continues to support national programmes and the aims of EU Directive 2013/55/EU in providing safeguards to professional mobility across European borders at a time when the demand for highly qualified professionals is increasing in the face of a disparity in their distribution across Europe. In support of achieving a CTF, the syllabus represents EFLM's position statement for the education and training that underpins the framework.

The harmonisation of growth hormone measurements: taking the next steps.

For over 20 years differences in results of growth hormone (GH) measurement have been recognised as being significant enough to lead to misdiagnosis and inappropriate management of patients with GH-related disorders. Whilst issues of method standardisation, variable antibody specificity, use of different reporting units with different conversion factors, and interference from GH binding protein have been acknowledged as contributing to the discrepancies, inconsistent approaches to method harmonisation have hampered opportunities to enhance the evidence base for GH measurements. Amongst the first steps to be taken, international collaboratives recommended the universal adoption of the International Standard 98/547 and the reporting of results in mass units. Whilst inter-method variability may have improved over the last 10 years, clinically significant differences remain. A more recently recognised issue contributing to the discrepancies may be the differences in the matrix materials used by kit manufacturers to assign values to their calibrants. The establishment of an international harmonisation oversight group is recommended: its key roles to include identification of a commutable matrix reference material, assessing the clinical significance of assay interferents, the evaluation of liquid chromatography-mass spectrometry as a reference measurement procedure and the provision of acceptance criteria for the clinical application of GH methods.

Partial growth hormone deficiency is associated with an adverse cardiovascular risk profile and increased carotid intima-medial thickness.

OBJECTIVE: To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GH deficiency (GH insufficiency, GHI). CONTEXT: Hypopituitary adults with untreated GH deficiency (GHD) have an excess vascular mortality and demonstrate clustering of adverse vascular risk factors. The vascular risk profile of GHI adults has yet to be comprehensively studied. DESIGN: A cross-sectional case controlled study. PATIENTS: Thirty GHD adults, 24 GHI, and 30 age- and sex-matched controls. GHI adults were defined biochemically using two GH stimulation tests (peak GH 3-7 µg/l). MEASUREMENTS: Serum lipids and apolipoproteins, plasminogen activator inhibitor type-I (PAI-I), C-reactive protein (CRP), lipoprotein (a) [Lp(a)], fibrinogen, blood pressure and carotid intima-medial thickness (IMT). RESULTS: IGF-I levels of GHI adults were lower than controls (373 ± 123 vs 295 ± 104 µg/l; P < 0.001). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) values were consistently between those of, but not significantly different from, GHD and control subjects. GHI adults showed significantly elevated PAI-I levels [80 (13-98) vs 50.5 (3-98) ng/ml; P = 0.01], although no there were differences in CRP, Lp(a), and fibrinogen levels compared with control subjects. No differences in systolic or diastolic blood pressure were shown between study groups. In parallel with the increased vascular risk profile of GH-insufficient adults, carotid IMT was significantly increased (0.503 ± 0.08 vs 0.578 ± 0.130 mm; P = 0.02). TC, LDL-C, Waist-Hip Ratio (WHR), truncal fat mass, and IMT correlated with IGF-I levels and GH status. TG, K(ITT), and PAI-I additionally correlated with GH status, but not with IGF-I levels. CONCLUSION: GHI adults are at elevated vascular risk, reflected by adverse surrogate markers and increased carotid IMT. The surrogate risk marker profile parallels GHD adults, but is less divergent from that observed in healthy individuals. No data are yet available as to whether these anomalies will be reflected in an increased vascular mortality in GHI adults.

Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan.

OBJECTIVE: Growth hormone deficiency (GHD) is associated with adverse changes in lipid profile. However, changes in lipids through life in a homogeneous group of GHD subjects have not been defined. PATIENTS AND MEASUREMENTS: We examined lipid levels in a group of untreated severely GHD patients with a mutation in the GHRH receptor gene from a rural community in North-east Brazil. Lipid profiles in 15 GHD subjects [eight children and adolescents (one male), age (median [range]) 13.2 (5.4-19.9) years; seven adults (one male), age 47 (33-66) years] were compared with those in 29 indigenous controls from the same extended kindred [17 children and adolescents (six male), age 10.2 (5.3-18.4) years; 12 adults (eight male), age 54.5 (33-80) years]. All GHD subjects had a peak GH response of < 0.5 ng/ml in response to an insulin tolerance test and extremely reduced IGF-1 levels (median 5.5 ng/ml). Data were compared between cohorts and with an age- and sex-matched white American reference population. RESULTS: Abnormalities were confined to plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. More GHD children had levels of plasma TC and LDL-C above the 95th percentile for our reference population (3/8 and 4/7, respectively) compared to controls (0/17 and 1/15, respectively) (P < 0.05). In the adults, median TC and LDL-C levels were higher in the GHD than controls (P < 0.05) (6.3 vs. 4.1 mmol/l; 4.4 vs. 2.7 mmol/l, respectively). Median Z-scores, calculated using values from the reference population, were not different between GHD children and adults for both TC (+0.8 vs.+0.4) and LDL-C (+1.4 vs.+0.7). CONCLUSIONS: The lipid profile in children as well as in adults with very severe GHD is adversely modified. There would appear to be no significant worsening of the lipid abnormality with duration of GHD or achievement of adulthood.

Comparison of apolipoprotein B metabolism in familial defective apolipoprotein B and heterogeneous familial hypercholesterolemia.

Both defective LDL receptors (familial hypercholesterolaemia, FH) and mutations in apolipoprotein B (apoB) on LDL (familial defective apoB, FDB) give rise to a phenotype of elevated LDL cholesterol. We sought to compare the metabolic basis of the two conditions by examining apoB turnover in FDB and FH subjects. A group comprising three heterozygous and one homozygous FDB subjects were compared with five FH heterozygotes and 17 control subjects using a deuterated leucine tracer. Kinetic parameters were derived by multicompartmental modelling. FH heterozygotes had a reduced delipidation rate for VLDL, which led to a moderate increase in plasma triglyceride. Compared with controls and FH, the FDB subjects converted 44% less IDL to LDL. The LDL FCR was reduced to a similar extent in FDB and FH. In all subjects LDL plasma levels appeared to be regulated by the LDL FCR and the rate of production of small VLDL. We conclude that disturbances in IDL metabolism provide the basis for understanding why FDB is less severe than FH. Our findings suggest that an apoB-LDL receptor interaction is important in the IDL to LDL conversion.