PARALLEL BIOCHEMICAL AND HISTOCHEMICAL STUDIES OF AN ADRENOCORTICAL ADENOMA FROM A PATIENT WITH PRIMARY ALDOSTERONISM

1961 ◽  
Vol 38 (2) ◽  
pp. 207-219 ◽  
Author(s):  
Jean Davignon ◽  
Gilles Tremblay ◽  
Wojciech Nowaczynski ◽  
Erich Koiw ◽  
Jacques Genest
Keyword(s):  
Primary Aldosteronism ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Morphological Aspect ◽  
Adrenocortical Adenoma ◽  
Acth Stimulation ◽  
Chromatographic Techniques ◽  
Striking Increase ◽  
Adrenal Tissue

ABSTRACT An adrenocortical adenoma surgically removed from a patient with primary aldosteronism was investigated by histological, histochemical and incubation-chromatographic techniques and compared to intact adrenal tissue excised from the contralateral gland. The tumour was composed almost entirely of fasciculata-like tissue and released »in vitro« cortisol, corticosterone, aldosterone, cortisone and 17-hydroxy-11-deoxycorticosterone but no measurable amounts of 11β-hydroxy-androstenedione. In contrast to the contralateral gland with prominent zona glomerulosa and atrophic zona fasciculata, which responded poorly to corticotrophin (ACTH) stimulation, the tumour responded by a striking increase in the formation of cortisol, corticosterone and aldosterone. An attempt was made to correlate the morphological aspect with the biochemical findings »in vitro«.

IN VITRO MODIFICATION OF RAT ADRENAL ZONA FASCICULATA/RETICULARIS FUNCTION BY THE ZONA GLOMERULOSA

1976 ◽  
Vol 81 (2) ◽  
pp. 340-350 ◽  
Author(s):  
G. P. Vinson ◽  
Barbara J. Whitehouse
Keyword(s):  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Equivalent Amount ◽  
Adrenal Tissue ◽  
Specific Analysis ◽  
Adrenal Zona Fasciculata ◽  
Preincubation Medium

ABSTRACT Following earlier findings, the possibility that the zona glomerulosa of the rat adrenal cortex may modify inner zone function was investigated. In a series of in vitro experiments designed to test this hypothesis it was found that: 1. Inner zone preparations gave significantly more steroid than either glomerulosa tissue incubated alone, or (for the first 40 min of a two hour incubation), an equivalent amount of whole adrenal tissue. Whole tissue yields were greater than glomerulosa alone only at the 120 min point. At no time did the whole tissue output approach the total anticipated by addition of separate inner zone and glomerulosa yields. 2. In 20 min incubations, inner zone steroid output generally could be depressed by the addition of a glomerulosa preincubation medium (PIM), or a steroid extract of a glomerulosa PIM, or by the addition of 100 ng aldosterone. Inner zone PIM had less effect. 3. Higher concentrations of aldosterone gave increased inhibition of inner zone corticosteroid production. The results indicated that only a part of the total corticosterone output was aldosterone sensitive in this way. 4. More specific analysis of the steroids showed that yields of corticosterone from endogenous precursors were depressed by aldosterone, but deoxycorticosterone and 18-hydroxydeoxycorticosterone were not. In the same incubations the presence of aldosterone had no effect on the formation of these three products from [3H]pregnenolone. In total the results suggest that the presence of the glomerulosa may affect inner zone function by inhibiting the secretion of corticosterone formed from endogenous precursors. It is possible that aldosterone is the agent of this effect.

Effects of angiotensin II and ACTH on normal and tumourous human adrenocortical cells

1983 ◽  
Vol 104 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Wolfgang Belmega ◽  
Wolfgang Oelkers ◽  
Lutz Belkien ◽  
Monika Shirpai ◽  
Ulrich Fiedler ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Adrenocortical Adenoma ◽  
Response Curves ◽  
Adrenocortical Cells ◽  
Normal Cells ◽  
Fold Stimulation

Abstract. Isolated adrenocortical cells from 6 patients with a 'normal' zona fasciculata, 4 patients with a 'normal' zona glomerulosa, and tumour cells from 1 adrenocortical adenoma and 1 carcinoma were incubated with and without increasing concentrations of ACTH 1–24 (10−13 m to 10−9 m) or Asp1-Ile5-angiotensin II (10−11 m to 10−7 m). In 4/5 'normal' cases, cortisol was clearly stimulated by 10−13 m ACTH. The maximum of the dose-response curve (5-fold stimulation) was reached at 10−10 m ACTH. Angiotensin II (All) started to stimulate 'normal' cells at 10−11 m with a maximum (2-fold stimulation) at 10−9 m. Aldosterone production by 'normal' cells was less markedly stimulated by ACTH and All, although the threshold doses for both peptides were similar to those of the cortisol response curves. The cells of the adrenocortical adenoma from a patient with Cushing's syndrome produced large amounts of cortisol and small amounts of aldosterone, both steroids being clearly stimulated by ACTH and AII. The adrenocortical carcinoma cells produced small amounts of cortisol and no aldosterone. Cortisol production responded to ACTH, but not to AII. The results suggest that an activated renin-angiotensin system may stimulate the zona fasciculata, since 10−11 m All (= 10 pg AII/ml) is a normal plasma All concentration on an unrestricted diet. Clinical evidence supporting this thesis is reviewed. However, cortisol production itself will rarely be increased by All in vivo, since a downregulation of ACTH would occur.

FORMATION OF STEROID HORMONES IN THE ADRENAL ADENOMA AND ADJACENT ADRENAL TISSUE OF A PATIENT WITH PRIMARY ALDOSTERONISM

1963 ◽  
Vol 41 (1) ◽  
pp. 1955-1959
Author(s):  
Elizabeth MacArthur ◽  
V. J. O'Donnell
Keyword(s):  
Adrenal Gland ◽  
Steroid Hormones ◽  
Primary Aldosteronism ◽  
Incubation Medium ◽  
Adrenal Adenoma ◽  
Adrenal Vein ◽  
Adrenal Tissue

The in vitro steroidogenic capacity of an adrenal adenoma and adjacent adrenal tissue of a patient with primary aldosteronism was studied. The adenoma slices elaborated into the incubation medium 7.07 μg/g tissue of cortisol (78.2%), corticosterone (7.6%), and aldosterone (14.2%), while the slices of adjacent adrenal gland released 19.88 μg/g tissue of cortisol (79.1%), corticosterone (14.9%), 11β-hydroxyandrostenedione (3.9%), androstenedione (2.1%), and a trace of aldosterone. The steroid content of the adenoma and the adrenal slices after incubation was 4.22 and 3.19 μg/g tissue respectively. From the former, cortisol (51.1%), corticosterone (36.6%), and progesterone (12.4%) were isolated and from the latter cortisol (13.2%), corticosterone (56.1%), progesterone (17.2%), and androstenedione (13.5%). A sample of adrenal vein blood obtained prior to adrenalectomy exhibited a cortisol/corticosterone ratio of 2.45.

scholarly journals Aldosterone secretion in patients with septic shock: a prospective study

2013 ◽  
Vol 57 (8) ◽  
pp. 636-641 ◽  
Author(s):  
Rafael Barberena Moraes ◽  
Gilberto Friedman ◽  
Marina Verçoza Viana ◽  
Tiago Tonietto ◽  
Henrique Saltz ◽  
...  
Keyword(s):  
Septic Shock ◽  
Serum Levels ◽  
Zona Glomerulosa ◽  
High Dose ◽  
Zona Fasciculata ◽  
Cortisol Secretion ◽  
Aldosterone Secretion ◽  
Acth Stimulation ◽  
Aldosterone Production ◽  
A Prospective Study

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

scholarly journals Primary Aldosteronism Associated with Multiple Adrenocortical Micronodules in a Patient with Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kazuhito Oba ◽  
Yuko Chiba ◽  
Yoko Matsuda ◽  
Takeshi Kumakawa ◽  
Rie Aoyama ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Primary Aldosteronism ◽  
Renal Cell ◽  
Zona Glomerulosa ◽  
Adrenocortical Adenoma ◽  
Loading Test ◽  
Cell Renal Cell Carcinoma ◽  
Aldosterone To Renin Ratio ◽  
The Right

A 47-year-old woman with a history of diabetes mellitus (DM) and obesity was admitted to our hospital for glucose control. She was detected to have hypertension (HT) and diagnosed with primary aldosteronism (PA) based on the high level of aldosterone to renin ratio and the results of the upright furosemide-loading test according to the criteria of the Japanese Society of Hypertension (JSH) guidelines. Computed tomography revealed left renal tumor and adrenocortical adenoma. She underwent left nephrectomy and adrenalectomy. The pathological findings were clear-cell renal cell carcinoma (RCC) and nonfunctional adrenocortical adenoma. Her nonneoplastic adrenal tissue histologically revealed CYP11B2-positive multiple adrenocortical micronodules (MNs) and concomitant paradoxical hyperplasia of the zona glomerulosa. Therefore, MNs were thought to be responsible for PA in this patient. After surgery, HT was improved, and the result of upright furosemide-loading test after 12 months of surgery did not fulfill the criteria of PA according to the JSH guidelines. However, the adrenocorticotrophic hormone stimulation test was positive; considering the possibility of slight aldosterone overproduction from the right adrenal gland, the administration of spironolactone was started. Herein, we report a rare case of RCC in conjunction with PA histologically associated with MNs.

IN VITRO RESPONSES OF FOCAL HYPERPLASTIC TISSUE OF THE HUMAN ADRENAL ZONA FASCICULATA TO ACTH

1977 ◽  
Vol 86 (2) ◽  
pp. 363-368 ◽  
Author(s):  
Kenneth V. Honn ◽  
Walter Chavin ◽  
Amnuay Singhakowinta
Keyword(s):  
Adrenocortical Function ◽  
Zona Fasciculata ◽  
Adrenal Tissue ◽  
Basal Cortisol ◽  
Aldosterone Production ◽  
Hyperplastic Tissue ◽  
Normal Human ◽  
Adrenal Zona Fasciculata ◽  
Normal Adrenal Tissue

ABSTRACT The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.

scholarly journals Oxygen-dependence of ACTH-stimulated aldosterone and corticosterone synthesis in the rat adrenal cortex: developmental aspects

2002 ◽  
Vol 172 (3) ◽  
pp. 595-604 ◽  
Author(s):  
ED Bruder ◽  
AK Nagler ◽  
H Raff
Keyword(s):  
Enzyme Activity ◽  
Age Groups ◽  
Maximal Activity ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Steroid Synthesis ◽  
Camp Generation ◽  
Aldosterone Production ◽  
Health And Disease

The control of ACTH-stimulated steroidogenesis under decreasing levels of O(2) is not fully understood. The purpose of this study was to examine the effects of decreased O(2) in vitro on rat adrenocortical steroid synthesis at different stages of development. Of interest was the evaluation of the effect of low O(2) on steroidogenesis during the stress hyporesponsive period of the neonate. Rats were killed at 7, 14, or 42 days of age, adrenals collected and capsules (zona glomerulosa, ZG) separated from subcapsules (zona fasciculata/reticularis, ZFR). Cells were dispersed and placed into glass vials each gassed with a different level of O(2) (21, 5, 2, 1, or 0% O(2)). The entire steroidogenic pathway was analyzed by measuring ACTH-stimulated cAMP, corticosterone and aldosterone production during a 2 h incubation. In addition, the early (P450 scc) and late (P450c11 beta and P450 aldo) pathway activities were examined in the presence of cyanoketone. The PO(2) for half-maximal activity (P(50)) for aldosterone synthesis in ZG cells from 7- and 42-day-old rats was approximately 28 mmHg and 7 mmHg respectively, indicating that cells from older rats were more resistant to inhibition by low O(2). The P(50) for cAMP production from the ZG was approximately 14 mmHg for both age groups. The P(50) for corticosterone synthesis was approximately 28 mmHg and <7 mmHg in ZFR cells from 7- and 42-day-old cells respectively. The only enzyme activities affected by low O(2) (<35 mmHg) were P450 aldo and P450 scc. Moderate decreases in O(2) (from approximately 150 mmHg) decreased aldosteronogenesis, possibly due to observed decreases in cAMP generation, but not due to decreases in steroidogenic enzyme activity (7-day-old). Severe decreases in O(2) presumably inhibited P450 aldo through a direct effect on enzyme activity (both ages). P450 scc activity (including cholesterol transport) also seems to be decreased by very low O(2) (7-day-old). These findings illustrate a novel developmental alteration in O(2)-regulated steroid production, and may have implications for neonatal health and disease.

In vitro conversion of cholesterol into aldosterone and cortisol in different zones of the bovine adrenal cortex

1982 ◽  
Vol 101 (3) ◽  
pp. 436-441 ◽  
Author(s):  
Karl-Eric Karlmar
Keyword(s):  
Adrenal Cortex ◽  
Total Content ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Oxidoreductase Activity ◽  
Chain Cleavage ◽  
Specific Fraction ◽  
The Individual ◽  
Cytochrome P 450

Abstract. The individual steps in the formation of aldosterone and cortisol from cholesterol were assayed in different subcellular preparations from the inner and outer zones of bovine adrenal cortex. In zona glomerulosa the 11β-, 18- and 21-hydroxylase activities were relatively high, whereas the 17α-hydroxylase activity was relatively low. Cholesterol side-chain cleavage and 3β-hydroxysteroid-Δ5-oxidoreductase activity were similar in zona glomerulosa and zona fasciculata-reticularis. The differences were however only quantitative. In no case one specific fraction was totally devoid of enzyme activity. The total content of mitochondrial cytochrome P-450 was relatively high in zona fasciculata-reticularis whereas the content of microsomal cytochrome P-450 was similar in the two fractions. In view of the relatively small differences observed, it seems likely that other factors than distribution of the above enzymes are of major importance for the specific production of gluco- and mineralocorticoids in the two layers.

EFFECT OF POTASSIUM INTAKE ON THE FINAL STEPS OF ALDOSTERONE BIOSYNTHESIS IN THE RAT

1972 ◽  
Vol 69 (4) ◽  
pp. 718-730 ◽  
Author(s):  
Klaus Baumann ◽  
Jürg Müller
Keyword(s):  
Incubation Medium ◽  
Adrenal Glands ◽  
Zona Glomerulosa ◽  
Selective Inhibitor ◽  
Potassium Deficiency ◽  
The Other ◽  
Zona Fasciculata ◽  
Hydroxylase Activity ◽  
Potassium Intake

ABSTRACT Incubated capsular adrenal glands (»zona glomerulosa«) of potassiumdeficient rats converted 57% less tritiated deoxycorticosterone to 11β-hydroxycorticosteroids and 45 % less tritiated cortexolone to cortisol than the capsular adrenals of potassium-replete rats. A similarly decreased conversion of cortexolone to cortisol was observed when capsular adrenal mitochondria were incubated. Potassium deficiency resulted in only a slight decrease in the rate of 11β-hydroxylation by decapsulated adrenals (»zona fasciculata-reticularis«). These findings indicate that the 11β-hydroxylase activity of the zona glomerulosa of the rat adrenal cortex is dependent on the potassium intake but to a lesser extent than 18-hydroxylase activity. We had previously observed that potassium deficiency induced a decreased production of aldosterone, an unchanged corticosterone output and an increased deoxycorticosterone output by capsular adrenals incubated with stimulating agents. The same alterations in endogenous corticosteroid production could be induced in vitro by the addition of a selective inhibitor of 18-hydroxylation (Su 8000) to the incubation medium. On the other hand, metopirone, i.e. an inhibitor of both 11β- and 18-hydroxylation, diminished corticosterone as well as aldosterone output by capsular adrenals. These results suggest that an increased deoxycorticosterone output by capsular adrenals may be due not only to a decrease in 11β-hydroxylase activity but may also be indirectly related to a decreased conversion of corticosterone to 18-hydroxycorticosterone and aldosterone.

scholarly journals Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

2015 ◽  
Vol 112 (33) ◽  
pp. E4591-E4599 ◽  
Author(s):  
Koshiro Nishimoto ◽  
Scott A. Tomlins ◽  
Rork Kuick ◽  
Andi K. Cani ◽  
Thomas J. Giordano ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Secondary Hypertension ◽  
Zona Glomerulosa ◽  
Driver Mutations ◽  
Molecular Characteristics ◽  
Zona Fasciculata ◽  
Adrenal Tissue ◽  
Somatic Gene ◽  
Aldosterone Production ◽  
Normal Adrenal Tissue

Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na+/K+transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA.

Sign in / Sign up

Export Citation Format

Share Document