Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery

1997 ◽  
Vol 136 (3) ◽  
pp. 290-295 ◽  
Author(s):  
Miklós Tóth ◽  
Károly Rácz ◽  
Ibolya Varga ◽  
Vilmos Adleff ◽  
Csilla Jakab ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Dehydroepiandrosterone Sulfate ◽  
High Plasma ◽  
Adrenal Tumors ◽  
Adrenal Surgery ◽  
Adrenocortical Tumors ◽  
Adrenocortical Adenomas ◽  
Before And After ◽  
Adrenocortical Carcinomas ◽  
Glucocorticoid Production

Abstract To investigate the clinical significance of plasma dehydroepiandrosterone sulfate (DHEAS) measurements, 175 patients with histologically confirmed adrenal tumors, 10 cortisol-producing adenomas, 59 aldosterone-producing adenomas, 56 non-hyperfunctioning adenomas, 13 adrenocortical carcinomas, 13 adrenal cysts, and 24 adrenomedullary tumors were studied. Plasma DHEAS levels were expressed as percentage of the mean of sex- and age-matched groups of healthy, normal subjects (DHEAS %). We found that before adrenal surgery, DHEAS % values were significantly reduced in patients with cortisol-producing (mean, 15·2% of control; 95% confidence interval (CI), 9·4–24·7%), non-hyperfunctioning (28·4%; 22·4–36·0% as well as aldosterone-producing adrenocortical adenomas (55·4%; 47·1–65·1%) compared with controls, while values were normal in patients with adrenal cysts and in those with adrenomedullary tumors. Plasma DHEAS % values exhibited a great variability in adrenocortical carcinomas (mean, 84·0%; 95% CI, 33·2–212·5%). Death from adrenocortical carcinoma was more frequent in patients with high plasma DHEAS % values compared with those with low DHEAS %. During long-term postoperative monitoring, we found that plasma DHEAS levels of patients with aldosterone-producing and non-hyperfunctioning adenomas returned to normal in the second and fourth postoperative year respectively. In patients with cortisol-producing adenomas, plasma DHEAS remained suppressed for as long as 8 years after the operation. These findings show that except in adrenocortical carcinomas and cysts, plasma DHEAS levels are significantly decreased in all groups of adrenocortical tumors, including non-hyperfunctioning and aldosteroneproducing tumors. The extent of this decrease and the postoperative persistence of suppressed plasma DHEAS levels may be related to the glucocorticoid production of adrenocortical tumors. European Journal of Endocrinology 136 290–295

scholarly journals The activating TERT promoter mutation C228T is recurrent in subsets of adrenal tumors

2014 ◽  
Vol 21 (3) ◽  
pp. 427-434 ◽  
Author(s):  
Tiantian Liu ◽  
Taylor C Brown ◽  
C Christofer Juhlin ◽  
Adam Andreasson ◽  
Na Wang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Transcriptional Activation ◽  
Recurrent Event ◽  
Adrenal Tumors ◽  
Promoter Mutation ◽  
Adrenocortical Adenomas ◽  
Cell Immortalization ◽  
Underlying Mechanisms ◽  
Adrenocortical Carcinomas ◽  
Promoter Mutations

The telomerase reverse transcriptase gene (TERT) encodes the reverse transcriptase component of the telomerase complex, which is essential for telomere stabilization and cell immortalization. Recent studies have demonstrated a transcriptional activation role for theTERTpromoter mutations C228T and C250T in many human cancers, as well as a role in aggressive disease with potential clinical applications. Although telomerase activation is known in adrenal tumors, the underlying mechanisms are not established. We assessed C228T and C250TTERTmutations by direct Sanger sequencing in tumors of the adrenal gland, and further evaluated potential associations with clinical parameters and telomerase activation. A total of 199 tumors were evaluated, including 34 adrenocortical carcinomas (ACC), 47 adrenocortical adenomas (ACA), 105 pheochromocytomas (PCC; ten malignant and 95 benign), and 13 abdominal paragangliomas (PGL; nine malignant and four benign).TERTexpression levels were determined by quantitative RT-PCR. The C228T mutation was detected in 4/34 ACCs (12%), but not in any ACA (P=0.028). C228T was also observed in one benign PCC and in one metastatic PGL. The C250T mutation was not observed in any case. In the ACC and PGL groups,TERTmutation-positive cases exhibitedTERTexpression, indicating telomerase activation; however, since expression was also revealed inTERTWT cases, this could denote additional mechanisms ofTERTactivation. To conclude, theTERTpromoter mutation C228T is a recurrent event associated withTERTexpression in ACCs, but rarely occurs in PGL and PCC. The involvement of theTERTgene in ACC represents a novel mutated gene in this entity.

DHEAS and Differential Blood Counts as Indirect Signs of Glucocorticoid Excess in Adrenal Non-Producing Adenomas

2021 ◽  
Vol 53 (08) ◽  
pp. 512-519
Author(s):  
Eliza P. Winzinger ◽  
Hana Jandikova ◽  
Matthias Haase ◽  
Andreas Knauerhase ◽  
Tudor Winzinger ◽  
...  
Keyword(s):  
Dexamethasone Suppression Test ◽  
Adrenal Tumors ◽  
Blood Concentrations ◽  
Adrenocortical Adenomas ◽  
Normal Individuals ◽  
Before And After ◽  
Suppression Test ◽  
Almost All ◽  
Dexamethasone Suppression ◽  
Glucocorticoid Action

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.

Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy

1989 ◽  
Vol 120 (2) ◽  
pp. 187-194 ◽  
Author(s):  
S. L. Hyer ◽  
P. S. Sharp ◽  
R. A. Brooks ◽  
J. M. Burrin ◽  
E. M. Kohner
Keyword(s):  
Normal Subjects ◽  
High Plasma ◽  
Prolonged Treatment ◽  
Somatostatin Analogue ◽  
Clinical Value ◽  
Gh Secretion ◽  
Treatment Regimens ◽  
Igf I ◽  
Before And After ◽  
Long Acting

Abstract. The response to GH releasing hormone (GHRH 1–29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 μg by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 μg/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU · l−1 · h−1;h 209 ± 81 vs 121 ± 82; P=0.01). Mean ± sd IGF-I levels (μg/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2–16) pump administration (203 ± 62 vs 60 ± 25; P= 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.

scholarly journals Histological scores and tumor size on stage II in adrenocortical carcinomas

Rare Tumors ◽  
2021 ◽  
Vol 13 ◽  
pp. 203636132110264
Author(s):  
Rui Caetano Oliveira ◽  
Maria João Martins ◽  
Carolina Moreno ◽  
Rui Almeida ◽  
João Carvalho ◽  
...  
Keyword(s):  
Tumor Size ◽  
Correct Diagnosis ◽  
Stage Ii ◽  
Adrenal Tumors ◽  
Median Size ◽  
Adrenocortical Adenomas ◽  
History Of ◽  
Aggressive Tumors ◽  
Adrenocortical Carcinomas ◽  
Worse Prognosis

Adrenocortical carcinomas (ACC) are aggressive tumors with a poor prognosis. Histological scores are advised for the diagnosis, however, there are borderline cases that may be misjudged as adrenocortical adenomas (ACA). The three main scores used are: Weiss Modified System (WMS), Reticulin Algorithm (RA), and Helsinki Score (HS). We intend to compare the accuracy of the three scores in ACC diagnosis and to identify predictive factors of overall survival (OS). Retrospective study (2004–2016) at Centro Hospitalar e Universitário de Coimbra of the adrenal tumors, classified as ACC or ACA, with a history of posterior tumor relapse/metastases, without lesions in the contralateral adrenal gland: 13F and 6M, with a median age of 51 ± 12.41 years. Nodules’ median size was 9.20 ± 6.2 cm. Patients had a median OS of 52 ± 18.6 months, with 57.9% and 46.3%, at 3 and 5 years. Seven patients had local recurrence and nine had metastases. Thirteen cases were in stage II. The WMS and the HS allowed a diagnosis of ACC in 15 cases and the RA defined ACC in 17 cases. All cases had, at least, focal disruption of the reticulin framework. More than 5 mitosis/50 HPF was associated with worse OS: 49.67 ± 21.43 versus 108.86 ± 14.02 months ( p = 0.026). In patients with stage II, tumor size ⩾10 cm was associated with worse OS: 19.25 ± 7.15 versus 96.11 ± 16.7 months ( p = 0.007), confirmed by multivariate analysis ( p = 0.031). The correct diagnosis of ACC is a pathologist responsibility. The RA seems the most accurate. Any loss of the reticulin framework should raise awareness for malignancy. In patients on stage II, a size ⩾10 cm is a predictor of worse prognosis.

scholarly journals Expression of the Chemokine Receptor CCR7 in the Normal Adrenal Gland and Adrenal Tumors and Its Correlation with Clinical Outcome in Adrenocortical Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5693
Author(s):  
Carmina Teresa Fuss ◽  
Katharina Other ◽  
Britta Heinze ◽  
Laura-Sophie Landwehr ◽  
Armin Wiegering ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Protein Expression ◽  
Chemokine Receptor ◽  
Adrenocortical Carcinoma ◽  
Distant Metastases ◽  
Adrenal Tumors ◽  
Mrna Levels ◽  
Primary Tumors ◽  
Adrenocortical Tumors ◽  
Adrenocortical Adenomas

Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients’ survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.

scholarly journals Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas

2009 ◽  
Vol 16 (2) ◽  
pp. 573-583 ◽  
Author(s):  
P S H Soon ◽  
A J Gill ◽  
D E Benn ◽  
A Clarkson ◽  
B G Robinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Gene Expression ◽  
Ki 67 ◽  
Adrenocortical Tumors ◽  
Reverse Transcription Pcr ◽  
Adrenocortical Adenomas ◽  
Microarray Profiling ◽  
High Discriminatory Power ◽  
Microarray Gene ◽  
Adrenocortical Carcinomas

The management of adrenocortical tumors (ACTs) is complex. The Weiss score is the present most widely used system for ACT diagnosis. An ACT is scored from 0 to 9, with a higher score correlating with increased malignancy. However, ACTs with a score of 3 can be phenotypically benign or malignant. Our objective is to use microarray profiling of a cohort of adrenocortical carcinomas (ACCs) and adrenocortical adenomas (ACAs) to identify discriminatory genes that could be used as an adjunct to the Weiss score. A cohort of Weiss score defined ACCs and ACAs were profiled using Affymetrix HGU133plus2.0 genechips. Genes with high-discriminatory power were identified by univariate and multivariate analyses and confirmed by quantitative real-time reverse transcription PCR and immunohistochemistry (IHC). The expression of IGF2, MAD2L1, and CCNB1 were significantly higher in ACCs compared with ACAs while ABLIM1, NAV3, SEPT4, and RPRM were significantly lower. Several proteins, including IGF2, MAD2L1, CCNB1, and Ki-67 had high-diagnostic accuracy in differentiating ACCs from ACAs. The best results, however, were obtained with a combination of IGF2 and Ki-67, with 96% sensitivity and 100% specificity in diagnosing ACCs. Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the two groups and is particularly helpful in ACTs with Weiss score of 3.

The Effect of Stapedectomy on the Loudness of One’s Own Voice

1965 ◽  
Vol 8 (3) ◽  
pp. 223-234 ◽  
Author(s):  
William Melnick
Keyword(s):  
Middle Ear ◽  
Normal Subjects ◽  
Sound Energy ◽  
Loudness Function ◽  
Before And After ◽  
Increased Sensitivity

Five subjects with normal middle ear mechanisms, and otosclerotic patients, before and after stapedectomy, matched the loudness of their voices to the loudness of a 125-cps-sawtooth noise. The results showed loudness matching functions with gradual slopes, less than 1.00, for the normal subjects and the patients prior to stapedectomy. Post-surgically, the loudness function for the patients increased in steepness to considerably more than 1.00. These results are explained, most logically, in terms of increased sensitivity of the altered middle ear to sound energy generated by the listener’s own voice.

BESTIMMUNG DER INSULINAKTIVITÄT IM MENSCHLICHEM SERUM NACH GLUKOSEBELASTUNG ALS PRÜFUNG DER FUNKTIONSFÄHIGKEIT DES PANKREAS

1963 ◽  
Vol 42 (3) ◽  
pp. 437-452 ◽  
Author(s):  
H. Daweke
Keyword(s):  
Blood Sugar ◽  
Pancreatic Insufficiency ◽  
Normal Subjects ◽  
Insulin Binding ◽  
Epididymal Adipose Tissue ◽  
Moderate Increase ◽  
Glucose Loading ◽  
Before And After ◽  
Oral Hypoglycaemic Drugs ◽  
Severity Of The Disease

Using the method of glucose-1-14C oxydation to 14CO2 on the rat epididymal adipose tissue, the insulin-like activities (ILA) in the serum have been compared before and after oral loading with glucose in normal subjects, in maturity-onset diabetics and in insulin-requiring diabetics. In maturity-onset diabetics mean fasting values were found to be 30% below normal while in insulin-requiring diabetics they were 85% above normal. In normal subjects there was observed, 30 minutes after glucose loading, a moderate increase in blood sugar together with an increase of ILA of 222% above the starting value; in maturity-onset diabetics the increase in ILA was only 106% while the blood sugar was markedly increased. After glucose loading in maturity-onset diabetics, the total amount of insulin detected during the period of the experiment was, on the average, only 45% of that found in normal subjects. In insulin requiring diabetics there was no increase but, on the contrary, a steady decrease of the ILA values, while the blood sugar excessively increased. In general ILA values were higher than those in maturity-onset diabetics. No difference in response was found between maturity-onset diabetics treated with diet alone and those treated with diet and oral hypoglycaemic drugs. In contrast to the absolute ILA values, the index of insulin reserve, is of value in assessing the functional capacity of the pancreas. This index decreases progressively with the severity of the disease and reaches a maximum of 54% of the normal in maturity-onset diabetics, which can satisfactorily be explained by pancreas insufficiency. Only in some cases of insulin-requiring diabetics was an insulin reserve still detectable. The biological inactivity of the insulin circulating in the blood can be deduced from the increased ILA-values, as compared with those found in maturity-onset diabetics. Obviously some of this insulin can be released by the addition of glucose. It is likely that, in addition to pancreatic insufficiency, insulin-binding or insulin-inactivating antibodies play a part in the pathogenesis of insulin-requiring diabetes.

DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo
Keyword(s):  
Thyroid Function Test ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Function Test ◽  
Before And After ◽  
Adrenal Response ◽  
Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

High Adrenocorticotropic Hormone before and after bilateral adrenal surgery

2018 ◽  
Author(s):  
Ana Valea ◽  
Roxana Turturea ◽  
Oana Botezan ◽  
Mara Carsote ◽  
Bogdan Mircea Botezan ◽  
...  
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Adrenal Surgery ◽  
Before And After
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