Steroid profile in urine: a useful tool in the diagnosis and follow up of adrenocortical carcinoma

Gröndal, Staffan; Eriksson, Barbro; Hagenäs, Lars; Werner, Sigbritt; Curstedt, Tore

doi:10.1530/acta.0.1220656

Cited by 59 publications

(35 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Urinary steroid analyses of our 5 ACC cases showed decreased 3β-HSD activity by increased 16HP5, PT5, and AT5 excretion, decreased 21 hydroxylase activity by increased 20αPT and Et excretion, and decreased 11β hydroxylase activity by increased 5βTHS excretion. Our data are consistent with those of previous studies [8,18]. Thus, it is reasonable to consider that the increased urinary metabolites of steroid precursors in ACC are most likely due to the "disorganized" expression of various steroidogenic enzymes by ACC [12].…”

Section: Gene Expression Profilesupporting

confidence: 92%

Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma

et al. 2011

View full text Add to dashboard Cite

AdrenocorticAl carcinoma (ACC) is a very rare neoplasm (incidence: 1-2/million) [1], which easily metastasizes to liver, lung, and bone, with a poor prognosis. With the recent advances in various imaging procedures, the detection of incidental adrenal mass has become more frequent, of which 2 to 12% are accounted for by ACC [2,3]. Therefore, it becomes more important to differentiate ACC from benign tumors such as adrenocortical adenomas (ACA). Functioning ACC Abstract. Adrenocortical carcinoma (ACC) is a very rare malignant tumor with poor prognosis. To gain insight into the pathogenic significance of ACC, we studied clinicopathological features and gene expression profile in ACC. We analyzed five ACC cases (two men and three women) with the median age of 45-year-old who underwent adrenalectomy at our institute. Endocrine studies revealed that two cases had subclinical Cushing's syndrome (SCS) and one with concomitant estrogen-secreting tumor, while the rest of three cases had non-functioning tumors. Analysis of urinary steroids profile by gas chromatography/mass spectrometry showed increased metabolites of corticosteroid precursors, such as 17-OH pregnenolone, 17-OH progesterone, dehydroepiandorosterone (DHEA), and 11-deoxycortisol in all five cases. The pathological diagnosis of ACC was based on Weiss's criteria with its score ≥ 3. The mean size of the resected tumors was 87 mm and Ki67/MIB1 labeling index, a proliferative marker, was 3 -27%. Immunohistochemical analysis revealed a disorganized expression of several steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and DHEA-sulfotransferase. Among several genes determined by RT-PCR, insulin-like growth factor (IGF)-II mRNA was consistently and abundantly expressed in all 5 tumor tissues. Postoperatively, two cases with SCS developed local recurrence and liver metastasis. The present study suggests that the disorganized expression of steroidogenic enzymes and the overexpression of IGF-II by the tumor are hallmarks of ACC, which could be used as biochemical and molecular markers for ACC.

show abstract

Section: Gene Expression Profilesupporting

confidence: 92%

Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma

et al. 2011

View full text Add to dashboard Cite

show abstract

“…It has been shown to be relevant as a diagnostic tool and as a tumor marker during follow-up (Grondal et al 1990). More recently, in a series of 102 patients with ACAs and 45 with ACCs, urinary steroid profiling differentiated ACCs from ACAs with a sensitivity and specificity of 90% (Arlt et al 2011).…”

Section: Geneticsmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

show abstract

“…17p-diol 11-OH AN 11 p-hydroxyandrostcronc 11-0 AN 11-oxo-androsterone 11-OET 11-oxo-ctiocholanolone 11-OHET 1 lp-hydroxyetiocholanolone 16a-OHDHA 16a-hydroxydehydroepiandrosterone PD pregnanediol PT pregnanetriol a 5-p d prcgn-5-ene-3p,20a-diol A5-ANT(16a) androst-5-ene-3P, 16a, 17p-triol THS letrahydro-11-deoxvcortisol A M 60H PN 16a-hydroxypregnenolone A5-PT ( 17) prcgn-5-ene-3p, 17a.20a-trio! THE tetrahydrocortisone A5-PT (16) pregn-5-ene-3p, 16a.20a-triol THB.…”

Section: Abbreviationmentioning

confidence: 99%

Heterogeneity of Urinary Steroid Profiles in Children with Adrenocortical Tumors

Małunowicz¹,

Ginalska-Malinowska²,

Romer

et al. 1995

Horm Res

View full text Add to dashboard Cite

The excretory patterns of urinary steroids determined by capillary gas chromatography in 11 children (aged 0.8-16.5 years) with adrenocortical tumors were established. In 8 patients the predominant clinical feature was virilization, in 3 others, Cushing’s syndrome. In 5 patients (3 carcinoma, 2 adenoma) very high excretion of 3β-hydroxy-5-ene steroids was observed. In 2 others (adenomas) only moderately elevated excretion of 11β-hydroxyandrosterone was found. In 1 patient (adenoma) pregnanediol dominated in the steroid profile, accompanied by moderately elevated 3β-hydroxy-5-ene steroids. Out of 3 Cushingoid patients (1 carcinoma, 2 adenomas), 1 presented an atypical urinary steroid pattern for hypercortisolemia, without 5α-reductase and 11β-hydroxysteroid dehydrogenase deficiencies. Neither the urinary steroid pattern nor tumor size alone were reliable indicators of tumor malignancy, as evaluated by a pathological examination and subsequent metastasis-free survival.

show abstract

Steroid profile in urine: a useful tool in the diagnosis and follow up of adrenocortical carcinoma

Abstract: coefficient of variation was between 6 and 21 % for the different steroids.

Cited by 59 publications

References 17 publications

Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma

Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Heterogeneity of Urinary Steroid Profiles in Children with Adrenocortical Tumors

Contact Info

Product

Resources

About