Juergen Kratzsch

Calcitonin (CTN) is a polypeptide hormone consisting of 32 amino acids with a disulfide bridge between position 1 and 7 that is mainly produced by the C-cells of thyroid gland. The measurement of CTN concentrations in blood reflects C-cell activity and is performed in general by immunoassay methods. However, there are analytical, physiological, pharmacological, and pathological factors that can influence results of serum CTN values. Due to the influence of these factors, there is a high variability in assay-dependent cutoffs used to discriminate between MTC, C-cell hyperplasia (CCH), and the absence of the pathological impairment of C-cells. There is a lot of evidence that the measurement of serum CTN concentrations in patients with thyroid nodules can lead to an earlier diagnosis of MTC or CCH than the exclusive use of imaging procedures and/or fine-needle aspiration cytology. Basal CTN concentrations higher than 60–100 pg/mL are highly indicative for the diagnosis MTC. In the range between cutoff and 60 pg/mL CTN, both MTC and HCC may be a relevant diagnosis. PCT and CTN appear to have a comparable diagnostic capability to diagnose MTCs. However, “positive” PCT values of more than 50 pg/mL may be reached also in subclinical infections and will lead, therefore, to an overdiagnosis of the tumor. Pentagastrin- or calcium-stimulated serum CTN concentrations higher than cutoff values might improve diagnostics of MTC, but the non-availability of the first and the lacking of relevant cutoff values for the second tool favors the use of only basal values currently.

Gender differences in the regulation of body-weight are well documented. Here, we assessed obesity-related influences of gender on brain structure as well as performance in the Iowa Gambling Task. This task requires evaluation of both immediate rewards and long-term outcomes and thus mirrors the trade-off between immediate reward from eating and the long-term effect of overeating on body-weight. In women, but not in men, we show that the preference for salient immediate rewards in the face of negative long-term consequences is higher in obese than in lean subjects. In addition, we report structural differences in the left dorsal striatum (i.e., putamen) and right dorsolateral prefrontal cortex for women only. Functionally, both regions are known to play complimentary roles in habitual and goal-directed control of behavior in motivational contexts. For women as well as men, gray matter volume correlates positively with measures of obesity in regions coding the value and saliency of food (i.e., nucleus accumbens, orbitofrontal cortex) as well as in the hypothalamus (i.e., the brain’s central homeostatic center). These differences between lean and obese subjects in hedonic and homeostatic control systems may reflect a bias in eating behavior toward energy-intake exceeding the actual homeostatic demand. Although we cannot infer from our results the etiology of the observed structural differences, our results resemble neural and behavioral differences well known from other forms of addiction, however, with marked differences between women and men. These findings are important for designing gender-appropriate treatments of obesity and possibly its recognition as a form of addiction.

The aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation. In archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and "In house"-RIA (Tübingen). The assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean ± SD) of values within the cut-off range was 24.3% ± 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and <1%, respectively. hGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence.

Objective: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. Materials and methods: Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (n = 25), during the first 18 h (mean ± S.D. 11.1 ± 4.3 h, n = 16) and 92 h (47.5 ± 22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. Results: The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P < 0.05). In contrast, leptin levels were significantly lower (P < 0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (r = −0.72), base excess (r = −0.70), and bicarbonate (r = −0.69) (P < 0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R variance. Conclusions: Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.

Background: The aim of our present study was to establish new reference intervals for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also assessed the effect of potentially confounding factors to modulate the limits of these intervals. Methods: We investigated 870 apparently healthy persons and excluded, step by step, those with a family history of thyroid disease, pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the entire group were finally included as reference collective. We measured serum concentrations of TSH, total and free thyroxine (T₄ and FT₄), and total and free triiodothyronine (T₃ and FT₃) of the whole and the reference collective on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and 97.5th percentiles for comparison. Results: The calculated lower limit for TSH differed significantly between the reference intervals for healthy persons with an assessed normal thyroid gland vs the nonselected group of healthy blood donors. Age was the only independent factor and was significantly inversely associated with TSH (P 4 concentrations (P 3 variations (P 4 vs FT₃ variation, gender and (inversely) age (P Conclusions: The selection of healthy persons according to NACB criteria combined with sonographic confirmation of a normal thyroid gland provide a valid basis for the reference interval for TSH. Factors indicating a preclinical disease state, such as family history, pathologic ultrasonography result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies, can be associated with normal hormone concentrations. Additionally, patient age and gender as well as use of contraceptives should be considered in diagnostic evaluation of thyroid diseases.

We aimed to evaluate the role of the soluble leptin receptor (sOB-R), the major leptin-binding protein in blood, for the regulation of growth and development of neonates. Therefore, human arterial and venous cord blood samples were taken from newborns of 45 healthy mothers to investigate correlations with anthropometric data. Furthermore, we compared changes in sOB-R and leptin in neonatal serum between postnatal d 1, 3, and 5. Cord blood levels of leptin (direct correlation) and the molar sOB-R/leptin ratio (inverse correlation) correlated significantly (P < 0.05) with weight, triceps, biceps, iliacal, and subscapular skinfolds at birth as well as on d 3 and 5 of life. During the first week of life, median leptin levels decreased significantly (P < 0.001) from 3.4 ng/ml in venous cord blood to 2.2 ng/ml in venous blood on d 1 after birth to 0.88 ng/ml on d 3 and 0.75 ng/ml on d 5. In contrast and most interestingly, median levels of sOB-R increased significantly (P < 0.001) from 14.5 ng/ml in cord blood to 18.9 ng/ml on d 1, 83 ng/ml on d 3, and 79.4 ng/ml on d 5. Consequently, the molar sOB-R/leptin ratio increased from 0.45 to 1.30 (d 1), 10.5 (d 3), and 13.7 (d 5) during the same period (P < 0.001). We found a remarkable postnatal change in the leptin-sOB-R axis with decreasing leptin and increasing sOB-R levels. Hence, the sOB-R may block leptin function by its competition with the membrane receptor for the ligand. These suppressive effects may be an important stimulus for energy uptake in the first week of life or in other conditions with a high energy demand.