Steroidogenesis in patients with adrenal incidentalomas: Extended steroid profile measured by liquid chromatography‐mass spectrometry after ACTH stimulation and dexamethasone suppression

Huayllas, Martha Katherine Paniagua; Smith, Lynette M.; Gallagher, J. Christopher; Netzel, Brian C.; Singh, Ravinder J.; Kater, Cláudio E.

doi:10.1111/cen.14445

Cited by 6 publications

(3 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first original result of this study is that the seven steroids studied, distributed on the three adrenal steroidogenesis pathways (glucocorticoids, androgens and mineralocorticoids), presented a higher amplitude of response to ACTH in patients with bilateral tumors (BL) not only in comparison to control subjects (CT) but also in comparison to patients with UL tumors. The only previous study comparing steroid profiles after ACTH stimulation between control subjects, UL and BL adrenocortical tumors ( 23 ) only looked at basal (T0) and stimulated (T60) steroid levels in absolute value and did not describe steroid amplitude of response to ACTH. Besides, patients’ recruitment was rather different: bilateral tumors only consisted in bilateral incidentalomas (no case of PBMAH reported).…”

Section: Discussionmentioning

confidence: 99%

Decreased steroidogenic enzyme activity in benign adrenocortical tumors is more pronounced in bilateral lesions as determined by steroid profiling in LC-MS/MS during ACTH stimulation test

Bonnet-Serrano

Barat

Vaczlavik

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

Objective: Large response of steroids precursors, including 17-hydroxyprogesterone, to ACTH has been described in adrenocortical tumors, suggesting the existence of intra-tumoral enzymatic deficiencies. This study aimed to compare steroidogenesis enzymes activity in unilateral and bilateral benign tumors using serum steroid profiling in LC-MS/MS in basal state and after ACTH 1-24 stimulation. Design and Methods: A serum profile of seven consecutive adrenal steroids was determined in LC-MS/MS in basal state (T0) and after ACTH 1-24 stimulation (T60) in 35 patients with bilateral adrenocortical tumors (BL), 38 patients with unilateral tumors (UL) and 37 control subjects (CT). Response amplitude of each individual steroid was evaluated by T60/T0 ratio whereas enzymatic activity was assessed by downstream/upstream steroid ratio. Adrenal volume was quantified by a semi-automatic segmentation method. Results: For the seven steroids assayed, the amplitude of response to ACTH was higher in BL than in UL and in CT. The difference between BL and UL persisted even after matching patients on adrenal volume. On glucocorticoids pathway, enzymatic activity of CYP11B1 was significantly decreased in BL (78.3 [43.1-199.4]) in comparison to both UL (122.7 [13.8-228.4], p = 0.0002) and CT (186.8 [42.1-1236.3], p<0.0001). On mineralocorticoids and androgens pathways, enzymatic activity of CYP11B2 and CYP17A1-17,20 lyase was also lower in BL than UL and CT. Conclusions: Decreased activity of distal steroidogenesis enzymes CYP11B1, CYP11B2 and CYP17A1-17,20 lyase, responsible for an explosive response to ACTH of upstream precursors in bilateral tumors, limits the synthesis of bioactive steroids, in particular cortisol, despite the increase in adrenal mass.

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased steroidogenic enzyme activity in benign adrenocortical tumors is more pronounced in bilateral lesions as determined by steroid profiling in LC-MS/MS during ACTH stimulation test

Bonnet-Serrano

Barat

Vaczlavik

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

show abstract

“…Eisenhofer et al 27 observed that additional preanalytical factors, such as age, weight and blood pressure may modify the ACTH response of this unique steroid, but we and others 17 have not checked for that. Moreover, increased 21DF levels are observed beyond CAH context, for example, subclinical cortisol adenomas, primary aldosteronism, adrenal incidentalomas and cholangiocarcinoma 28–32 ; conversely, 21OHD HZ status has not also been investigated in these conditions 33 …”

Section: Discussionmentioning

confidence: 99%

Reassessment of predictive values of ACTH‐stimulated serum 21‐deoxycortisol and 17‐hydroxyprogesterone to identify CYP21A2 heterozygote carriers and nonclassic subjects

Costa-Barbosa

Carvalho

Oliveira

et al. 2021

Clinical Endocrinology

Self Cite

View full text Add to dashboard Cite

Introduction Heterozygotes (HZs) for 21‐hydroxylase deficiency (21OHD) are highly prevalent, ranging from 1:60 to 1:11 for classic and nonclassic (NC) forms, respectively. Detection of HZ and asymptomatic NC by CYP21A2 genotyping is valuable for genetic counselling, but costly, complex and narrowly available. Adrenocorticotropic hormone (ACTH)‐stimulated serum 17‐hydroxyprogesterone (17P) and 21‐deoxycortisol (21DF) discriminate 21OHD phenotypes effectively, notably if measured simultaneously by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Objective This study was performed to reassess former LC‐MS/MS‐defined post‐ACTH 21DF, 17P and cortisol (F) cutoffs in family members at risk for 21OHD. Design and Patients Prospective study in which we screened 58 asymptomatic relatives from families with 21OHD patients and compared post‐ACTH steroid phenotypes with subsequent genotypes. Results Post‐ACTH 21DF, 17P, F and (21DF + 17P)/F ratio segregate NC, HZ and wild‐type (WT) phenotypes (subsequently genotyped) with some overlap. New receiver operating characteristic curve‐defined cutoffs for post‐ACTH 21DF, 17P and (21DF + 17P)/F ratio are 60 ng/dl, 310 ng/dl and 12 (unitless). Twenty‐six of 33 HZ and all 6 NC (82.1%) had post‐ACTH 21DF > 60 and 17P > 310 ng/dl, whereas 17/19 WT (89.5%) had values below cutoffs. Post‐ACTH 21DF and 17P had a strong positive correlation (r = .9558; p < .001). A (21DF + 17P)/F ratio > 12 correctly identified 36 of 39 HZ plus NC (92.3% sensitivity) with 84.2% specificity (16 of 19 WT). Given the high frequency of 21OHD HZ, the negative prediction of ratio values below 12 excludes heterozygosity in 99.8% and 99.1% for classic and NC mutations, respectively. Conclusions Reassessed ACTH‐stimulated 21DF and 17P cutoffs by LC‐MS/MS (60 and 310 ng/dl, respectively) correctly recognised 82.5% HZ plus NC, but combined precursor‐to‐product ratio ([21DF + 17P]/F) cutoff of 12 was superior, identifying 92.3% HZ plus NC. Since one WT subject is an outlier (potential HZ), these values would be somewhat better reinforcing their utility for screening asymptomatic relatives at risk for 21OHD.

show abstract

“…Their synthesis is controlled by the Hypothalamic Pituitary Adrenal axis and the Hypothalamic Pituitary Gonadal axis and they have roles in many physiological and pathophysiological processes. Measuring panels of steroids is important clinically in assessing endocrine function, reproductive health and in cancer [2] , [3] , [4] and also in veterinary care and welfare in animals [5] , [6] , [7] .…”

Section: Introductionmentioning

confidence: 99%

A practical approach to supported liquid extraction and measurement of 18 steroids in plasma and serum by targeted liquid chromatography tandem mass spectrometry

Denham,

Simpson,

Diez

et al. 2024

MethodsX

View full text Add to dashboard Cite

Steroidogenesis in patients with adrenal incidentalomas: Extended steroid profile measured by liquid chromatography‐mass spectrometry after ACTH stimulation and dexamethasone suppression

Cited by 6 publications

References 41 publications

Decreased steroidogenic enzyme activity in benign adrenocortical tumors is more pronounced in bilateral lesions as determined by steroid profiling in LC-MS/MS during ACTH stimulation test

Decreased steroidogenic enzyme activity in benign adrenocortical tumors is more pronounced in bilateral lesions as determined by steroid profiling in LC-MS/MS during ACTH stimulation test

Reassessment of predictive values of ACTH‐stimulated serum 21‐deoxycortisol and 17‐hydroxyprogesterone to identify CYP21A2 heterozygote carriers and nonclassic subjects

A practical approach to supported liquid extraction and measurement of 18 steroids in plasma and serum by targeted liquid chromatography tandem mass spectrometry

Contact Info

Product

Resources

About