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  • Author: Bjørn O Åsvold x
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Free access

The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study

Bjørn O Åsvold, Lars J Vatten, Tom I L Nilsen, and Trine Bjøro

Objective: The association between TSH and serum lipids in people with no apparent thyroid disease is insufficiently understood. We have studied the association between normal thyroid function, defined as TSH within the reference range of a general population, and concentrations of serum lipids.

Design: Cross-sectional, population-based study with 30 656 individuals without known thyroid disease.

Methods: Using general linear models, we calculated mean concentrations of total serum cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, HDL cholesterol and triglycerides across categories of TSH.

Results: Within the reference range of TSH, there was a linear and significant (P for trend <0.001) increase in total serum cholesterol, LDL cholesterol, non-HDL cholesterol and triglycerides, and a linear decrease (P for trend <0.001) in HDL cholesterol with increasing TSH. Subgroup analyses showed statistically significant associations for all lipids in men above 50 years of age, and for triglycerides in all age groups. For women, associations were statistically significant in all age groups except for HDL cholesterol in women below 50 years of age. The associations with triglycerides and HDL cholesterol were stronger among overweight than normal weight individuals.

Conclusions: Within the range of TSH that is considered clinically normal, we found that increasing level of TSH was associated with less favourable lipid concentrations. The association with serum lipids was linear across the entire reference range of TSH.

Open access

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls

Elin Pettersen Sørgjerd, Robin Mjelle, Vidar Beisvåg, Arnar Flatberg, Valdemar Grill, and Bjørn O Åsvold

Objective

Diabetes is a heterogeneous disease and a precise diagnosis of diabetes subgroups is necessary to initiate proper early treatment and clinical management of the disease. Circulating small RNAs (sRNAs) are potentially diagnostic biomarkers in diseases, including diabetes. Here we aimed to examine whether profiles of circulating sRNAs differed between patients with autoimmune and non-autoimmune diabetes and non-diabetic controls.

Design

This cross-sectional case–control study included participants from the third survey of the HUNT study.

Methods

We performed sRNA sequencing in serum from adult-onset type 1 diabetes (n = 51), type 2 diabetes (n = 50) and latent autoimmune diabetes in adult (LADA, n  = 51), as well as non-diabetic HUNT3 participants as control group (n = 51). Differential expression analysis of the sRNAs was performed in R using limma-voom.

Results

We identified differences in sRNA expression between autoimmune (type 1 diabetes and LADA) and non-autoimmune diabetes (type 2 diabetes) and between patients with diabetes and non-diabetic controls. Focusing on miRNA, we identified 10 differentially expressed mature miRNAs and 30 differentially expressed miRNA variants (isomiRs). We also identified significant changes within other sRNA classes, including a pronounced downregulation of a tRNA fragment in patients with diabetes compared to non-diabetic controls. We created cross-validated sRNA signatures based on the significant sRNAs that distinguished patients with diabetes from non-diabetic controls, and autoimmune from non-autoimmune diabetes, with high specificity and sensitivity. sRNA profiles did not distinguish between type 1 diabetes and LADA.

Conclusions

Circulating sRNAs are differentially expressed between patients with diabetes and non-diabetic controls and between autoimmune and non-autoimmune diabetes.

Free access

Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test

Grethe Å Ueland, Paal Methlie, Ralf Kellmann, Marit Bjørgaas, Bjørn O Åsvold, Ketil Thorstensen, Oskar Kelp, Hrafnkell B Thordarson, Gunnar Mellgren, Kristian Løvås, and Eystein S Husebye

Objectives

The overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum.

Design and methods

Prospective study of DST was carried out in patients with suspected Cushing’s syndrome (CS) (n = 49), incidentaloma (n = 152) and healthy controls (n = 101). Cortisol, cortisone and DXM were assayed by liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Results

Three hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST (n = 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort (n = 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol.

Conclusions

Simultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS.