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Results for “ADRENAL CORTEX HYPERFUNCTION”

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PubMed1992

Atriopeptin: an endogenous corticotropin-release inhibiting hormone.

Activation of the hypothalamic-pituitary-adrenocortical axis is a major component of the body's response to stress. Current theories on the pathophysiology of disorders associated with hyperfunction of the axis, such as depression and Cushing's stress, are based on the concept that anterior pituitary adrenocorticotropin (ACTH) secretion is stimulated by hypothalamic corticotropin-releasing hormones and inhibited by adrenal corticosteroids. Hypothalamic inhibitory control of pituitary ACTH secretion has been also postulated, but has not gained general acceptance because of the lack of definitive evidence for a corticotropin-release inhibiting hormone. It is shown here that in conscious rats stress-induced secretion of ACTH and corticosterone is markedly enhanced by the immunoneutralisation of atriopeptin. Therefore, we propose that atriopeptin is a physiologically relevant corticotropin-release inhibiting hormone.

Adrenal Cortex↗

PubMed1999

Relationship between clear cell/compact cell ratio and computed tomographic attenuation number in adrenocortical adenoma.

Clear cell/compact cell ratio in histologic sections from 21 resected adrenocortical adenomas was assessed. Seven patients had Cushing's syndrome another 7 had primary aldosteronism caused by adrenal adenomas and 7 had non-hyperfunctioning adenomas. The results were correlated with the corresponding unenhanced CT attenuation numbers. There was a negative correlation between clear cell/compact cell ratios and unenhanced CT attenuation numbers. However, CT attenuation numbers did not show significant differences between cortisol-producing, aldosterone-producing and nonfunctioning adenomas. These facts suggest that clear cell/compact cell ratio in adrenocortical adenomas accounts for their attenuation number on unenhanced CT scans. However, it is difficult with the use of unenhanced CT attenuation numbers to differentiate cortisol-producing adenomas from aldosterone-producing and nonhyperfunctioning adenomas.

Adrenal Cortex Neoplasms↗

PubMed1997

The analysis of steroidogenic activity in non-hyperfunctioning adrenocortical adenoma.

The steroidogenic activities in non-hyperfunctioning adrenal adenoma (NHFA) have not yet been fully examined. Steroid content both in adenoma and its non-tumorous adjacent adrenal tissue was measured by the HPLC system in 8 cases of NHFA and 2 cases of preclinical Cushing's syndrome (PCS). Activities of cytochrome P450c17alpha, P450c21, P450c11beta, P450c18 and aldosterone-synthesizing enzyme (P450aldo) were also determined by the enzyme reconstitution system. Steroid content in NHFA varied but no significant difference was seen between NHFA and normal control adrenals. Activities of all P450s except P450aldo were confirmed in NHFA, but they were almost equivalent to those in normal control adrenals. As no significant difference between NHFA and normal controls was observed in either steroid contents or P450s activities, the steroidogenic activity of NHFA is considered to be comparable to that of normal adrenals.

Adenoma↗

PubMed1988

Trabecular bone morphometry in beagles with hyperadrenocorticism and adrenal adenomas.

Trabecular bone morphometry was done on rib samples of beagles with hyperadrenocorticism and adrenal adenomas to evaluate bone loss and the remodeling changes responsible. Beagles diagnosed as having clinical hyperadrenocorticism and those with milder or subclinical hyperadrenocorticism diagnosed on the basis of adrenal and pituitary lesions at necropsy had increased adrenal and pituitary gland weights. In a group of dogs with adrenal cortical adenomas there was atrophy of remaining cortex, and the combined weight of adrenal glands or pituitary weights were not increased. In dogs with clinical hyperadrenocorticism, mean trabecular bone volume was 25% less than controls (P = 0.10). In both clinical and subclinical hyperadrenocorticism groups, the extent of trabecular surface with unmineralized osteoid matrix and osteoblasts was significantly reduced. There were no changes in resorption surfaces or number of osteoclasts present. No bone changes were seen in dogs with adrenal adenomas. In dogs with hyperadrenocorticism it appeared that decreased bone formation was primarily responsible for the relative osteopenia that developed. Although parathyroid glands were moderately enlarged in those dogs for which weights were available, the bone changes were not those of increased remodeling expected in hyperparathyroidism.

Adenoma↗

PubMed1990

Sub-clinical Cushing's syndrome in patients with adrenal gland incidentalomas. Pitfalls in diagnosis and management.

Widespread use of contemporary imaging techniques (ultrasound, computerized axial tomography, and magnetic resonance imaging scans) have led to the incidental discovery of asymptomatic adrenal neoplasms with increasing frequency. Patients with such adrenal "incidentalomas" typically have no clinical manifestations of adrenal cortical hyperfunction at the time of discovery. We have studied 122 patients with asymptomatic adrenal masses ranging in size from 2 to 7 cm in diameter from 1978 to 1988. Selected patients, after adrenal metastases, pheochromocytoma, myelolipomas, and cysts were ruled out, were further evaluated for adrenal cortical hyperfunction by measuring urinary 17-hydroxysteroids, 17-ketosteroids, and free cortisol, serum A.M., P.M. cortisol, and plasma ACTH levels. These values were also measured before and after dexamethasone suppression. NP-59 adrenal scintiscans were performed on all patients. Six patients were identified with sub-clinical Cushing's syndrome. Baseline cortisol levels were normal in each of these patients. Loss of diurnal rhythm appeared to be the most sensitive indicator of abnormal adrenal cortical function. When adrenalectomy is performed in such patients, especially when contralateral adrenal gland suppression is evidenced by NP-59 scanning or other biochemical assessment, perioperative steroids should be administered in a manner similar to that used for patients with symptomatic Cushing's syndrome. Unilateral adrenalectomy in a patient with an asymptomatic adrenal adenoma, insufficiently studied, may result in Addisonian crisis.

Adenoma↗

PubMed2004

Role of the inhibin/activin system and luteinizing hormone in adrenocortical tumorigenesis.

Adrenal masses are one of the most common endocrine tumors diagnosed. Although most adrenal tumors are inactive adenomas, a considerable proportion is associated with hormonal hyperfunction and/or malignancy. The adrenocortical carcinoma (ACC) is a rare but highly malignant tumor. Most ACCs in adults are diagnosed in an advanced tumor stage limiting therapeutic options. Accordingly, despite some progress in diagnostic and therapeutic approaches, the overall survival rate of patients with ACC remains poor. However, the prerequisite for the development of new diagnostic tools and therapeutic options in the management of patients with ACC is the elucidation of the molecular pathogenesis of adrenal tumorigenesis. Although our understanding of adrenal tumor biology has increased substantially over the last decades, the regulation of many molecular pathways involved in adrenocortical growth and differentiation awaits further elucidation. Luteinizing hormone (LH) and activin have only recently emerged as hormones likely to play opposite roles in adrenocortical hormone secretion and cellular proliferation. Recent evidence from studies on human surgical tumor sample expression and detailed characterization of murine adrenal tumor models suggests stimulatory effects of LH on adrenocortical growth and function. On the contrary, activin, which plays a critical role as a paracrine and autocrine factor regulating cellular growth and differentiation, has been demonstrated to induce apoptosis and suppress proliferation in the human and murine adrenal cortex. In this review, we will summarize molecular and functional aspects of adrenal tumorigenesis and highlight some prospects for future clinical applications.

Activins↗

PubMed2002

Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas.

BACKGROUND: The presence and pathophysiological role of CYP11B1 (11beta-hydroxylase) gene in the zona glomerulosa of human adrenal cortex is still controversial. METHODS: In order to specifically quantify CYP11B1, CYP11B2 (aldosterone synthase) and CYP17(17alpha-hydroxylase) mRNA levels, we developed a real-time RT-PCR assay and examined the expression in a series of adrenal tIssues, including six normal adrenals from patients adrenalectomized for renal cancer and twelve aldosterone-producing adenomas (APA) from patients with primary aldosteronism. RESULTS: CYP11B1 mRNA levels were clearly detected in normal adrenals, which comprised both zona glomerulosa and fasciculata/reticularis cells, but were also measured at a lower range (P<0.05) in APA. The levels of CYP11B2 mRNA were lower (P<0.005) in normal adrenals than in APA. CYP17 mRNAlevels were similar in normal adrenals and in APA. In patients with APA, CYP11B2 and CYP11B1 mRNA levels were not correlated either with basal aldosterone or with the change from basal aldosterone in response to posture or to dexamethasone. No correlation between CYP11B1 mRNA or CYP11B2 mRNA and the percentage of zona fasciculata-like cells was observed in APA. CONCLUSIONS: Real-time RT-PCR can be reliably used to quantify CYP11B1 and CYP11B2 mRNA levels in adrenal tIssues. Expression of CYP11B1 in hyperfunctioning zona glomerulosa suggests an additional formation of corticosterone via 11beta-hydroxylase, providing further substrate for aldosterone biosynthesis. CYP11B1 and CYP11B2 mRNA levels in APA are not related to the in vivo secretory activity of glomerulosa cells, where post-transcriptional factors might ultimately regulate aldosterone production.

Adenoma↗

PubMed1995

No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms.

The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis.

Adolescent↗

PubMed1997

Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors: implications for tumorigenesis.

Constitutive activating mutations of G protein-coupled receptors, such as that of TSH, have been implicated in the tumorigenesis of human endocrine neoplasms, such as thyroid adenomas. In a previous study we reported that constitutive activating point mutations of the ACTH receptor (ACTH-R) gene, a member of the G protein-coupled receptor superfamily, were not present in hormone-secreting and nonsecretory adrenocortical neoplasms. In this study, we investigated whether allelic loss of the ACTH-R gene is present in sporadic adrenal tumors. We identified a PstI polymorphism in the promoter region 3 kilobases upstream of the coding region of the ACTH-R gene. The rate of heterozygosity for this polymorphism in 99 unrelated Caucasian individuals was 53.5%. Using this polymorphism, we analyzed loss of heterozygosity (LOH) of the ACTH-R gene in 20 informative cases with benign and malignant adrenocortical tumors. Of 16 patients with benign lesions, LOH was present in 1 oncocytic nonfunctional adenoma, but not in 15 hyperfunctioning adenomas. Of 4 informative patients with adrenocortical carcinomas, LOH was present in 2 cases. Both patients had advanced tumor stages and showed a more rapid course than carcinoma patients without LOH. Analysis of the flanking region of the ACTH-R using the polymorphic microsatelite marker D18S37 and D18S40 showed that this deletion was confined to the ACTH-R gene. Northern blot experiments demonstrated reduced expression of ACTH-R messenger ribonucleic acid in the tumors with LOH of the ACTH-R gene, suggesting functional significance of this finding at the transcriptional level. We conclude that LOH of the ACTH-R gene is possibly involved in adrenal tumorigenesis, contributing to cellular dedifferentiation in adenomas and carcinomas.

Adenoma↗

PubMed1989

Immunohistochemical study of cytochrome P-45017 alpha in human adrenocortical disorders.

Cytochrome P-450 specific for steroid 17 alpha-hydroxylation (P-45017 alpha) was immunolocalized in normal and hyperfunctioning adrenal glands of pigs, bovines, and humans, using a specific IgG fraction raised against the enzyme. P-45017 alpha was present in the zona fasciculata (ZF) and zona reticularis (ZR), but not in the zona glomerulosa (ZG), in pig, bovine, and human adrenal glands. In the adrenal glands of patients with Cushing's disease, the positive immunoreactivity to P-45017 alpha was intense in ZF and ZR, particularly in cortical micronodules, corresponding to the sites of active steroidogenesis. Cells of hyperplastic ZG and outer ZF in the adrenal glands of idiopathic hyperaldosteronism were negative for P-45017 alpha. In aldosteronoma, positive immunoreactivity was observed in some tumor cells, which is consistent with cortisol production and its responsiveness to ACTH in aldosteronoma. In the attached adrenal glands of aldosteronoma, the immunoreactive P-45017 alpha was clearly present in the inner ZF and ZR, suggesting persistent androgen production. In Cushing's adenoma, the positive immunoreactivity was intense in tumor cells, and the ZR of the attached adrenal glands was weakly immunoreactive.

Adenoma↗

PubMed2005

A case of adrenal gland dependent hyperadrenocorticism with mitotane therapy in a Yorkshire terrier dog.

Hyperadrenocorticism, a disorder characterized by excessive production of cortisol by the adrenal cortex, is well-recognized in dogs. A 10-year-old, intact male, Yorkshire terrier dog was evaluated because of corneal ulceration and generalized alopecia. Diagnosis was made based on history taking, clinical signs, physical examination, and results of routine laboratory testing (complete blood count, serum biochemical analysis, and urinalysis). In addition, adrenocorticotropic hormone (ACTH) stimulation test and abdominal ultrasonography were also used to diagnose this case. The patient was diagnosed as adrenal gland neoplasia and medical therapy using the adrenocorticolytic agent, mitotane, was initiated. An ACTH stimulation test was performed after initial therapy. After successful induction was obtained, maintenance therapy with mitotane still continued.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Neurodevelopmental liabilities in schizophrenia and affective disorders.

There is now considerable evidence that both schizophrenia and affective disorders have their origin at least in part in events that occur during early pre- and post-natal development. In the case of schizophrenia, many observations, for example, increased risk for schizophrenia in the offspring of mothers who had influenza A during their second trimester of pregnancy and evidence for abnormal neuronal migration in the cerebral cortex of post mortem tissue from schizophrenic patients, suggest that a second trimester insult may have occurred and that this insult may have increased the risk for the development of schizophrenia in late adolescence or early adulthood. Animal studies have found that rats that undergo exocitotoxic damage to the ventral hippocampus on postnatal day 7 develop exaggerated sensitivity to dopamine-stimulating drugs or to stressful stimuli that becomes apparent after sexual maturity but not before, providing a neurodevelopmental model of schizophrenia. Similarly, post-weaning social isolation leads to enhanced responses to dopaminergic drugs and to stress that emerges after sexual maturity. These animal models are proving to be valuable tools to study the neurobiological mechanisms mediating the influence of early insults to the nervous system on later behavioural functions. In the case of affective disorders, although the evidence is not as strong, a number of the same observations have been made suggesting that an insult during early ontogeny may lead to the development of affective disorders later in life. For example, retrospective studies of people with affective disorders showed that they were more likely to have attained motor milestones at a later age and to have had poorer academic performance as children. There is a wealth of evidence suggesting hyperfunctioning of the hypothalamic-pituitary-adrenal (HPA) axis in affective disorders. Animal studies have shown that early maternal deprivation can lead to lasting changes in the reactivity of the HPA axis to stressful stimuli, providing another link from early experience to adult psychopathology. Continued studies of the effects of pre- and early post-natal events on the development of the nervous system and the relationships of these events to schizophrenia or affective disorder will provide new insights into the mechanisms underlying these common neuropsychiatric illnesses.

Journal Article↗

PubMed1992

Corticoid production by four dogs with hyperfunctioning adrenocortical tumours during treatment with mitotane (o,p'-DDD).

In two dogs with hyperadrenocorticism due to an adrenocortical tumour, treatment with o,p'-DDD was started. Their hormonal response was monitored by measurements of the urinary corticoid/creatinine ratio. In one dog, two courses of 10 days treatment with o,p'-DDD were ineffective, whereas in the other dog the urinary corticoids decreased to very low levels after only six days of treatment, and corticosteroid supplementation had to be started. Two other dogs received o,p'-DDD according to a protocol used for the treatment of pituitary-dependent hyperadrenocorticism which aims at the complete destruction of the adrenal cortices, with substitution for the induced hyperadrenocorticism. Both dogs made a good recovery and their urinary corticoid/creatinine ratio decreased to within the reference range. In one of them the tumour had decreased considerably in size by five weeks after the start of the treatment.

Adenoma↗

PubMed1999

[Differential diagnosis of space-occupying adrenal masses].

Computed tomography (CT) and magnetic resonance (MR) imaging are first line modalities in the evaluation of patients with adrenal gland masses, and have the potential to be very accurate for the localization of adrenal gland masses in patients with diseases associated with hyperfunctioning conditions of the adrenal gland. Both CT and MR imaging allow a specific diagnosis of acute adrenal hemorrhage, adrenal myelolipoma, and adrenal cysts. CT is also helpful in the assessment of patients with Addison's disease, particularly the subacute form secondary to granulomatous diseases. Quantitative evaluation of adrenal masses on unenhanced CT scans and/or qualitative analysis on chemical-shift MR imaging have been shown to be accurate in distinguishing adrenal adenomas from non-adenomas. Attenuation of 11 HE or less on unenhanced CT scans and/or signal loss on opposed phase MR images indicate adenoma with a high specificity and acceptable sensitivity. More recently, delayed-enhanced CT has yielded higher sensitivity and specificity values in distinguishing between adrenal adenomas and non-adenomas than both unenhanced CT and chemical-shift MR imaging do. On delayed-enhanced CT scans, adrenal adenomas exhibit a greater washout of contrast material than do adrenal non-adenomas. Therefore, adrenal non-adenomas have significantly higher attenuation than adenomas on delayed-enhanced CT scans obtained at several arbitrarily chosen time points (3-60 min) after the initiation of contrast material administration.

Adenoma↗

PubMedDate not supplied

[Change in the level of acid-soluble adenine nucleotides in rat tissues in experimental hypo- and hypercorticism].

The level of free adenine nucleotides was studied in the rat tissues in deficiency and excess of the adrenal cortex hormones in the organism. Hypocorticism induced by adrenalectomy led to reduction of the concentration of total and individual adenine nucleotides in all the tissues examined, except ADP in the spleen and AMP in the myocardium. Single administration of hydrocortisone to intact rats caused an increase in the level of total and individual adenine nucleotides in the liver and reduction of their concentration in the spleen and the skeletal muscle. Along with a fall of total nucleotides and ADP concentration in the myocardium, the AMP content increased and the ATP remained unchanged. Experiments carried out pointed to the participation of glucocorticoids in the metabolism of free tissue adenine nucleotides. Specificity of the reaction of individual tissues to the changes in glucocorticoid hormones level in the organism was noted.

Adenosine Diphosphate↗

PubMed1986

Primary pigmented nodular adrenocortical disease: diagnosis and management.

A rare cause of Cushing's syndrome appearing to originate in the adrenal glands is primary pigmented nodular adrenocortical disease (PPNAD). It may be variably associated with a complex of other pathologic characteristics that include cardiac myxomas, cutaneous myxomas, and lentigines, mammary myxoid lesions, testicular tumors, pituitary adenomas, and neuroectodermal tumors. We have reviewed the clinical, biochemical, radiographic, operative, and pathologic details of seven patients with PPNAD who have been evaluated at Mayo Clinic. Biochemical testing supported autonomous adrenal hyperfunction. This was based on the failure of cortisol suppression by high-dose dexamethasone, failure of pituitary stimulation by metyrapone administration, either normal or suppressed basal adrenocorticotropic hormone (ACTH) levels, normal radiographic studies of the sella turcica, and normal abdominal and thoracic computerized tomography in search of an ectopic ACTH-producing tumor. Six patients underwent bilateral total adrenalectomy without postoperative complications. Nelson's syndrome has not occurred, but acute adrenocortical insufficiency may have contributed to the death of one patient. To recognize the possible diagnosis of PPNAD preoperatively is important to proceed directly with adrenalectomy, avoiding unnecessary pituitary surgery. Moreover, if PPNAD is part of the broader pathologic complex, the possible presence of cardiac myxomas that may be multiple, recurrent, in atypical locations, and familial must be borne in mind.

Adolescent↗

PubMedDate not supplied

CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome.

Adrenocorticotropic hormone (ACTH)-independent hypercortisolism accounts for 15%-20% of cases of Cushing syndrome and always arises from primary adrenal disease. Computed tomographic (CT) and magnetic resonance (MR) imaging findings in 37 patients with primary adrenal Cushing syndrome were analyzed and correlated with pathologic findings. Hyperfunctioning adenomas (n = 24), together with functioning carcinomas (n = 10), accounted for 92% of cases. Adenomas had a significantly smaller mean size (3.5 vs 14.5 cm) and lower mean unenhanced CT attenuation value (11 vs 28 HU) than did carcinomas. The presence of necrosis, hemorrhage, and calcification favored a diagnosis of carcinoma. Six of 10 carcinoma patients had metastases at presentation. Two adenomas were seen within a myelolipoma, which was recognized at both CT and MR imaging due to its fat content, and two adenomas were of uncertain malignant potential. Bilateral disease--primary pigmented nodular adrenal dysplasia (PPNAD) (n = 2) and ACTH-independent macronodular adrenal hyperplasia (AIMAH) (n = 1)--had characteristic imaging features. In PPNAD, multiple tiny (2-5-mm) nodules were visible bilaterally, with no overall glandular enlargement and normal intervening adrenal tissue. In AIMAH, both glands were grossly enlarged and contained nodules up to 3 cm in diameter. Familiarity with the range of imaging appearances of the adrenal glands in primary adrenal Cushing syndrome may help establish the underlying diagnosis.

Adenocarcinoma↗

PubMed1981

Effect of functional adrenocortical tumors on plasma cortisol and corticotropin concentrations in dogs.

Plasma endogenous adrenocorticotropic hormone (ACTH) concentrations as well as basal and post-ACTH-stimulation plasma cortisol concentrations were measured in 6 dogs ultimately shown to have hyperfunctioning adrenocortical tumors. The basal and post-ACTH-stimulation plasma cortisol concentrations were found to fluctuate in 4 dogs in which repeat studies were done. Three dogs had at least 1 normal and 1 abnormally high plasma cortisol concentration after exogenous ACTH administration. A 4th dog had 1 normal and 1 abnormally high resting cortisol concentration. One dog tested twice 3 days apart had similar test results each time and a 6th dog was tested once. All of the dots had at least 1 plasma endogenous ACTH concentration greater than 2 standard deviations below the normal mean. All endogenous ACTH concentrations were less than those previously reported for dogs with pituitary-dependent hyperadrenocorticism. The results indicated that the diagnosis of adrenocortical tumor cannot reliably be made on the basis of the plasma cortisol response to exogenous ACTH; however, the use of plasma endogenous ACTH determination can be an important diagnostic aid.

Adenoma↗