dexamethasone suppression test
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2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacob M. Maskal ◽  
Luiz F. Brito ◽  
Alan W. Duttlinger ◽  
Kouassi R. Kpodo ◽  
Betty R. McConn ◽  
...  

AbstractIn utero heat stress alters postnatal physiological and behavioral stress responses in pigs. However, the mechanisms underlying these alterations have not been determined. The study objective was to characterize the postnatal hypothalamic–pituitary–adrenal axis response of in utero heat-stressed pigs. Pigs were subjected to a dexamethasone suppression test followed by a corticotrophin releasing hormone challenge at 10 and 15 weeks of age. Following the challenge, hypothalamic, pituitary, and adrenal tissues were collected from all pigs for mRNA abundance analyses. At 10 weeks of age, in utero heat-stressed pigs had a reduced (P < 0.05) cortisol response to the corticotrophin releasing hormone challenge versus controls. Additionally, the cortisol response tended to be greater overall (P < 0.10) in 15 versus 10-week-old pigs in response to the dexamethasone suppression test. The cortisol response tended to be reduced overall (P < 0.10) in 15 versus 10-week-old pigs in response to the corticotrophin releasing hormone challenge. Hypothalamic corticotropin releasing hormone mRNA abundance tended to be greater (P < 0.10) in in utero heat-stressed versus control pigs at 15-weeks of age. In summary, in utero heat stress altered some aspects of the hypothalamic–pituitary–adrenal axis related to corticotropin releasing hormone signaling, and age influenced this response.


Author(s):  
Natalia Genere ◽  
Ravinder Jeet Kaur ◽  
Shobana Athimulam ◽  
Melinda A Thomas ◽  
Todd Nippoldt ◽  
...  

Abstract Context Interpretation of dexamethasone suppression test (DST) may be influenced by dexamethasone absorption and metabolism and by the altered cortisol binding Objective We aimed to determine the normal ranges of free cortisol during DST in participants without adrenal disorders, and to identify the population of patients where post-DST free cortisol measurements add value to the diagnostic work up. Design and Setting Cross-sectional study conducted in a tertiary medical center Participants Adult volunteers without adrenal disorders (n=168; 47 women on oral contraceptive therapy (OCP), 66 women not on OCP, 55 men) and patients undergoing evaluation for hypercortisolism (n=196; 16 women on OCP) Measurements Post-DST dexamethasone and free cortisol (mass spectrometry) and total cortisol (immunoassay). Main Outcome Measures Reference range for post-DST free cortisol, diagnostic accuracy of post-DST total cortisol. Results Adequate dexamethasone concentrations (≥0.1 mcg/dL) were seen in 97.6% volunteers and 96.3% patients. Only 25.5% of women volunteers on OCP had abnormal post-DST total cortisol (&gt;1.8 mcg/dL). In volunteers, the upper post-DST free cortisol range was 48 ng/dL in men and women not on OCP, and 79 ng/dL in women on OCP. When compared to post-DST free cortisol, diagnostic accuracy of post-DST total cortisol was 87.3% (95%CI 81.7-91.7); all false positive results occurred in patients with post-DST cortisol between 1.8 and 5 mcg/dL. OCP use was the only factor associated with false positive results (21.1% vs 4.9%, p=0.02). Conclusions Post-DST free cortisol measurements are valuable in patients with optimal dexamethasone concentrations and post-DST total cortisol between 1.8 and 5 mcg/dL.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andreas Chatzittofis ◽  
Adrian Desai E. Boström ◽  
Diana M. Ciuculete ◽  
Katarina Görts Öberg ◽  
Stefan Arver ◽  
...  

AbstractDNA methylation shifts in Hypothalamic–pituitary–adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kang Chen ◽  
Shi Chen ◽  
Lin Lu ◽  
Huijuan Zhu ◽  
Xiaobo Zhang ◽  
...  

ContextTraditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing’s syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.ObjectivesTo develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.Design and SettingSingle-center retrospective study (2011–2019).PatientsTwo hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.ResultsFor the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p &lt; 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of &lt;26%, the sensitivity and specificity of LDDST were 39.4% and 100%. We designed a new pathway in which BIPSS was only reserved for those patients with unsuppressed LDDST and adenoma &lt;6mm, yielding an overall sensitivity of 97.7% and specificity of 86.7%.ConclusionLDDST had similar value to HDDST in differentiating CD and EAS using the specific cutoff point. The pathway that combined LDDST and BIPSS could differentiate CD and EAS accurately.


2021 ◽  
Vol 14 (8) ◽  
pp. e244258
Author(s):  
Annalisa Montebello ◽  
Etienne Ceci Bonello ◽  
Miriam Giordano Imbroll ◽  
Mark Gruppetta

A 55-year-old woman presented with a 4-month history of right-sided non-specific loin pain and 6 kg weight loss. A CT scan of the abdomen and pelvis showed an incidental 4.5 cm right-sided adrenal lesion which was not typical of an adrenal adenoma. This was further confirmed on MRI of the adrenals. Biochemical investigations to investigate for a functional adrenal lesion included serum catecholamines and metanephrines, an aldosterone to renin ratio and an overnight dexamethasone suppression test. These were all negative. A laparoscopic adrenalectomy was performed in view of the large size of the lesion. Histology was consistent with a phaeochromocytoma, which confirmed the diagnosis of a non-secreting phaeochromocytoma. Non-secreting phaeochromocytomas are rare and usually found in patients with known genetic mutations. Adrenal lesions not related to any mutations similar to our case are even rarer and reported even less in the literature.


2021 ◽  
Vol 53 (08) ◽  
pp. 512-519
Author(s):  
Eliza P. Winzinger ◽  
Hana Jandikova ◽  
Matthias Haase ◽  
Andreas Knauerhase ◽  
Tudor Winzinger ◽  
...  

AbstractThe majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.


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