Atrophy Of Adrenal Cortex Research Articles

Adrenal insufficiency - causes and laboratory diagnosis.

Adrenal insufficiency (AI) manifests as a clinical syndrome arising from either the direct impairment of adrenal glands, leading to primary AI characterized by deficiencies in glucocorticoids and mineralocorticoids, or adrenal cortex atrophy due to diminished adrenocorticotropic hormone (ACTH) stimulation, a consequence of hypothalamic and/or pituitary damage, resulting in secondary AI. The diagnosis of AI is based on clinical assessment and biochemical tests, including basal hormone level measurements and stimulation tests. In evaluating the results of laboratory tests, it is necessary to consider factors that may influence both pre-analytical and analytical phases, as well as the chosen methodology. Correct diagnosis of adrenal insufficiency and timely initiation of suitable replacement therapy are paramount. These steps are crucial not only for managing the condition but also to avert potentially life-threatening adrenal crises.

Acute Transcriptional Effects of Dexamethasone on Mouse Adrenal Gland Transcriptome

Researchers have long known that dexamethasone causes cellular and functional changes in the adrenal gland. For example, long-term dexamethasone treatment leads to reversible adrenal cortex atrophy. In the adrenal medulla, dexamethasone treatment alters the maturation and function of the neural crest-derived chromaffin cells. Here we aim to study the acute transcriptional effect of dexamethasone on mouse adrenal gland at the transcriptome level. Our data suggested that a one-hour dexamethasone treatment had a cell type-specific effect on the adrenal transcriptome. There were 922 dexamethasone-induced genes and 853 dexamethasone-suppressed genes. GO analysis showed that the upregulated genes were primarily linked to neuronal cell function. Clustered heatmaps further showed that many genes involved in the catecholamine synthesis were upregulated by dexamethasone treatment, whereas most genes involved in the steroidogenesis pathway were downregulated. Interestingly, steroidogenic factor 1 (SF1, encoded by Nr5a1), the critical transcription factor that regulates steroidogenesis, had a >2-fold decrease under the one-hour dexamethasone treatment, suggesting a possible mechanism of the acute suppression of steroidogenic activity. Our findings indicate that the acute effects of dexamethasone stimulate catecholamine synthesis in the medulla, whereas steroidogenesis in the cortex is suppressed by dexamethasone.

Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination in the central nervous system and to adrenal cortex atrophy. In 2016, X-ALD was added to the US Recommended Uniform Screening Panel. To evaluate the performance of a single-tier newborn screening assay for X-ALD in North Carolina. This diagnostic screening study was of all newborn dried blood spot specimens received in the North Carolina State Laboratory of Public Health between January 2 and June 1, 2018, excluding specimens of insufficient quantity or quality. A total of 52 301 specimens were screened for X-ALD using negative ionization high-performance liquid chromatography tandem mass spectrometry to measure C24:0- and C26:0-lysophosphatidylcholine concentrations. Sanger sequencing of the adenosine triphosphate-binding cassette subfamily D member 1 (ABCD1) gene was performed on screen-positive specimens. A medical and family history, newborn physical examination, sequencing of ABCD1 on dried blood spot samples, and plasma analysis of very long-chain fatty acids were obtained for all infants with screen-positive results. The prevalence of X-ALD in North Carolina and the positive predictive value and false-positive rate for the first-tier assay were determined. Of 52 301 infants tested (47.8% female, 50.6% male, and 1.7% other or unknown sex), 12 received screen-positive results. Of these 12 infants, 8 were confirmed with a genetic disorder: 3 male infants with X-ALD, 3 X-ALD-heterozygous female infants, 1 female infant with a peroxisome biogenesis disorder, and 1 female infant with Aicardi-Goutières syndrome. Four infants were initially classified as having false-positives results, including 3 female infants who were deemed unaffected and 1 male infant with indeterminate results on confirmatory testing. The positive predictive value for X-ALD or other genetic disorders for the first-tier assay was 67%, with a false-positive rate of 0.0057%. This newborn screening pilot study reported results on 2 lysophosphatidylcholine analytes, identifying 3 male infants with X-ALD, 3 X-ALD-heterozygous female infants, and 3 infants with other disorders associated with increased very long-chain fatty acids. These results showed successful implementation in a public health program with minimal risk to the population. The findings will support other state laboratories planning to implement newborn screening for X-ALD and related disorders.

Dexamethasone-induced adrenal cortex atrophy and recovery of the gland from partial, steroid-induced atrophy.

This study aims to examine the effects of low dexamethasone (DX) doses on cellular and functional changes in the rat adrenal cortex and to observe the recovery of the gland from DX-induced partial atrophy. Within seven days doses of 15, 30 and 60 micrograms DX/100 g/day resulted in a dose dependent decrease in body and adrenal gland weight. Within two weeks the lowest DX dose tested caused further decrease in adrenal weight. DX markedly lowered plasma ACTH and corticosterone (B) level, B content in the gland and B output by adrenal slices. Adrenocortical atrophy induced by 15 micrograms DX was dependent upon the linear decrease in the volume of fasciculata and reticularis zones, in the average volume of the fasciculata cell and in the number of adrenocortical cells in the entire cortex. This dose of DX resulted in a prompt and potent inhibition of proliferative activity of adrenocortical cells as assessed by the counting of metaphases per adrenal section. Partial adrenal atrophy evoked by 7 day DX-treatment was reversible within seven days of the discontinuation of the steroid treatment. Recovery of the gland depended mainly on the increases in the volume of all adrenocortical zones, in the average volume of fasciculata cell and in the number of parenchymal cells in the gland. Seven days after discontinuation of DX administration plasma ACTH was significantly higher than in controls. Plasma B and B secretion by adrenal slices were similar to the control group while B content in the gland was still depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of cells expressing Jun and Fos proteins and synthesizing DNA in the adrenal cortex of hypophysectomized rats: regulation by ACTH and FGF2

Protein expression of the early response genes, jun and fos, has been suggested to play an important role in the in vitro and in vivo proliferation of adrenal cells. To elucidate the immunolocalization of proliferative cells and the patterns of adrenal gland expression of members of the activating protein-1 (AP-1) family of oncogenes, we used hypophysectomized rats. The effects of adrenocorticotropic hormone (ACTH) and fibroblast growth factor 2 (FGF2) on Fos and Jun protein expression were investigated, and DNA synthesis was assessed by using bromodeoxyuridine (BrdU) incorporation. No change was detectable in the adrenal cortex at 2 days after hypophysectomy, although a reduction occurred in the number of BrdU-positive cells in the zona fasciculata. This hypophysectomy-induced early phase of adrenal cortex atrophy in the zona fasciculata was correlated with JunB protein induction, suggesting the formation of an inhibitory AP-1 complex. Accumulation of c-Jun/JunD and c-Fos/FosB, but not of JunB, in the zona fasciculata and zona reticularis implied that, after ACTH stimulation, these proteins were the principal AP-1 components in these zones. In these same zones, ACTH increased BrdU-positive cell counts, indicating that the composition of the AP-1 complex in these zones was proliferation-related. However, FGF2 induced an antagonistic modulation of the response to ACTH, by reducing the numbers of Jun-/Fos-positive cells and inhibiting DNA synthesis. Our results implicate the AP-1 family of transcription factors (in particular, the dynamics within the Jun protein family) in the regulation of cell control during ACTH-induced proliferation of the adrenal cortex.

The effect of long-term exposure to combinations of growth promoters in Long Evans rats: Part 2. Adrenal morphology (histopathology and immunochemical studies)

The aim of the study was to investigate the effects of long-term exposure (45 days) to growth promoters: clenbuterol (CB: 1mgkg−1bw) and/or dexamethasone (DEX: 0.1mgkg−1bw), in adrenal gland morphology, and the possibility of recovery after the withdrawal of drug treatment. Animals were sacrificed at different days of withdrawal (W0, W5, W10, W15 and W20), and adrenal glands processed for histopathology and immunohistochemistry. Adrenals of CB treatment showed typical features of long-term administration of β-agonists at W0 such as capillary dilatation in the fasciculata-reticularis zone, and this feature was also presented at W20. Adrenals of CB+DEX treatments showed the same results of CB treatment at days W0 and W20. However, DEX treatment presented the typical results of the exposure to corticoids with the atrophy of adrenal cortex. Immunohistochemistry of adrenal cortex steroidogenic enzymes (P450: scc, 3β-HSD, aromatase) denoted that neither positive staining nor localization was affected by treatments. Aromatase enzyme was immunolocalized in adrenal medulla cells in controls as well as in treated groups. The immunolocalization of glucocorticoid receptors showed an increase in CB (+++) and CB+DEX (++) treatments compared to the control group (0) and DEX treatment (0). Histopathological and immunohistochemical results are closely related to those found for adrenal endocrine function. We can conclude that chronic administration of growth promoters influence adrenal morphology and glucocorticoid receptor expression.

Neonatal seizures and retardation in a girl with biochemical features of X‐linked adrenoleukodystrophy

Neonatal hypotonia, seizures beginning at 5 days, and severe retardation were noted in a girl with normal karyotype and biochemical evidence of impaired adrenal function. Postmortem examination at 14 months revealed malformative and destructive lesions of central gray and white matter, atrophy of adrenal cortex with striated adrenocortical cells, hepatic fibrosis, and PAS-positive macrophages in several organs. Pathologically and clinically, this patient most closely approximated neonatal adrenoleukodystrophy (ALD) and differed strikingly from X-linked childhood ALD. In contrast, biochemical changes resembled the abnormalities observed in X-linked ALD and differed from those in the neonatal form. The very-long-chain fatty acid accumulation characteristic of both disorders was demonstrated, but unlike neonatal ALD, the levels or metabolism of plasmalogens, pipecolic acid, phytanic acid, and bile acid intermediates were normal, and peroxisomes in a liver biopsy specimen were present in normal number and appeared enlarged. While the case resembles the recently reported entity of peroxisomal acyl-CoA oxidase deficiency, assignment to this category was excluded by immunoblot studies on postmortem liver, which revealed normal amounts of this enzyme. Correlation of clinical, morphologic, and biochemical data suggests that this case is an example of a so-far undescribed entity, and reinforces the concept that the phenotypic spectrum of peroxisomal disorders is wider than realized.

Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -6. Subacute toxicity in dogs by percutaneous administration (author's transl)

The percutaneous subacute toxicity of 0.1% and 0.5% hydrocortisone 17-butyrate 21-propionate ointment (0.1% HBP, 0.5% HBP) were studied in beagle dogs for 3 months at the daily dose level of 200 mg per kilogram of body weight, using 0.1% and 0.5% hydrocortisone 17-buyrate ointment (0.1% HB, 0.5% HB), 0.12% and 0.5% betamethasone 17-butyrate ointment (0.12% BV, 0.5% BV) as the reference drugs. The results in this study were as follows : 1) In the sites applied HBP, HB and BV, acne-like changes and inhibition of hair growth wore found. 2) Body weight, food and water consumptions increased in the groups of 0.5% ointment, and in these dogs obesity by accumlation of subcutaneous fat was observed. 3) In hematological examination, biochemical examination and urinalysis, decrease in the number of lymphocytes and eosinophils, and increase in total cholesterol, triglyceride, urine-volume and urine-potassium were observed at 0.5% ointment groups. 4) In autopsy, dose-induced weight loss of thymus and adrenals, and hemorrhage of gastromucosa were found in dogs applied HBP, HB and BV. 5) In histopathological examination, the atrophy of adrenal cortex, lymphatic tissues, bone marrow, prostate, uterus and skin were found in dogs applied HBP, HB and BV. Further more, enlargement of hepatocytes was found. The above changes common other corticosteroids, which have been already reported, returned to normal after I month recovery period at 0.1% or 0.12% ointment groups. The percutaneous toxicity study of HBP compared with HB and BV was perfofmed. As the result, HBP and HB were almost samely toxic, but slightly less toxic than BV.

Studies on the adrenal cortex of hypophysectomized rats: A model for abnormal cellular atrophy and death

Biochemical and ultrastructural studies indicate that the atrophy of adrenal cortex in hypoyhysectomized rats involves the following changes: (1) One to two days after hypophysectomy, there is loss of "template activity" resulting from cumulative DNA-damage and heterochromatinization. In vivo ACTH-administration led to recuperation of these cells, indicating damage during hypophysectomized state to be reversible. (2) If the duration of hypophysectomy is prolonged, some of the cells become irreversibly damaged and can no longer recuperate after in vivo ACTH administration. (3) The period of most rapid cell death is from the third to seventh day after hypophysectomy. The cause of cell death is probably due to membrane damage in the absence of protein synthesis, leading to lysis of the cells. Lysozomes and macrophages are apparently not involved.

DISSOZIATION DER BIOLOGISCHEN UND ENZYMINDUZIERENDEN AKTIVITÄTEN VON PREDNISON-21-GLYCYLGLYCINAT UND ANDROST-4-EN-3-ON-17-AMINO

ABSTRACT 1. The biological effects and the induction of the glutamic-pyruvic-transaminase (G. P. T.) of the liver and of the carbonic-acid-anhydratase (C. A.) of the seminal vesicle produced by the administration of prednisone-21-glycylglycinate (PGG), androst-4-en-3-one-17-amino (aminotestosterone) and the corresponding free steroid alcohols has been investigated in intact and adrenalectomized male golden hamsters and in intact male rats. 2. The administration of PGG has no effect on the survival period in adrenalectomized animals and does not lead to adrenal cortex atrophy in intact animals. However, it increases the weight of the liver and induces an increase of the G. P. T. of the liver significantly. 3. Although aminotestosterone and testosterone increase the concentration of the C. A. of the seminal vesicles to the same degree, aminotestosterone was found to have only very weak androgenic and anabolic activity. 4. The significance of the dissoziation between the enzyme inducing and the biological activities of the compounds studied is discussed.

Barbituarte potentiating action of DDD and perthane.

ConclusionsTech. DDD, recrystalized DDD, supernatant mother liquor of Tech. DDD, and Tech. Perthane cause prolonged sleeping time in dogs given sodium pentobarbital. This increased sleeping time is not seemingly related to atrophy of adrenal cortex, and the very slight amount of fatty change in the liver does not cause prolonged clearance of barbiturates from the blood. This prolonged sleeping time is not obtained with similar doses of Tech. DDD in the rat although a slight lowering of tolerance to anoxia may result.

Acute adrenal cortical insufficiency; precipitation by infection during prolonged cortisone treatment.

There is considerable evidence that cortisone from either exogenous or endogenous sources can cause a suppression of the function of the adrenal cortex. In 1935 Kepler noted that patients with a hyperfunctioning adrenal cortical tumor would have atrophy of the contralateral adrenal cortex and that these patients on occasion would die in a state of shock and collapse. 1 Ingle produced atrophy of the adrenal cortex in rats by administration of large amounts of cortin. 2 It has been demonstrated in humans that histopathological alterations occur in the adrenal cortex after the administration of cortisone. These changes include reduction in the total weight of the gland, narrowing and pallor of the cortex, and loss of lipid. 3 The depression of adrenal cortical function by cortisone has been further demonstrated by observing that cortisone-treated patients fail to respond in the usual manner to test doses of corticotropin. It has been shown

Effect of hypothalamic lesions on steroid-induced atrophy of adrenal cortex in the dog.

Summary1. Normal dogs, dogs with lesions of the median eminence, and dogs with lesions elsewhere in the brain were subjected to left adrenalectomy, then treated with hydrocortisone for 14 days and their right adrenals removed. Some of the animals received 50 mg of hydrocortisone for a day and the remainder received 6.25 mg every other day. 2. Normal dogs showed a 20% decrease in adrenal weight and histologic atrophy on the larger steroid dose, while the smaller dose produced no weight change, being just sufficient to prevent the expected compensatory adrenal hypertrophy. 3. Dogs with destruction of the median eminence of the hypothalamus show no atrophy of the left adrenal removed one month after their lesions were produced, and the same degree of decline in adrenal weight after administration of the larger dose of steroid as the controls. On the other hand, they show a 9% decrease in adrenal weight on the smaller dose of hydrocortisone. 4. Dogs with hypothalamic lesions sparing the median eminence show e...

Addison's disease in a five and one-half year old boy.

Chronic adrenal insufficiency (Addison's disease) is extremely rare in the pediatric age group. In the approximately 100 such cases that have appeared in the literature to date, less than one fourth of the patients were children under 10 years of age. 1 Adrenocortical tuberculosis was etiologically responsible for the majority of cases, whereas a smaller percentage was ascribed to bilateral adrenal cortex atrophy, agenesis or degeneration of unknown origin and hyperplasia of the adrenogenic zone of the cortex. Other etiologic factors responsible for the destruction of the adrenal cortex and the syndrome of Addison's disease in adults, namely, pyogenic abscesses, vascular lesions, mycosis fungoides, echinococcic cysts, amyloidosis, neoplasms, histoplasmosis, moniliasis and diphtheria, have not been demonstrated in children. 2 Because of the relative rarity of Addison's disease in infancy and early childhood, the following case of the disease due to bilateral adrenal cortex atrophy in a 5½ year old boy

INFLUENCE OF ADRENAL CORTEX EXTRACT UPON COMPENSATORY HYPERTROPHY OF THE ADRENAL CORTEX

When one adrenal is removed the cortex of the remaining gland undergoes hypertrophy.1 This does not occur if the hypophysis is removed simultaneously, and in time if hypophysectomy is done, the cortex of the remaining gland, or if the animal has both glands, all of the cortical tissue, atrophies.2 Cortical repair follows anterior pituitary transplants.3 An anterior pituitary extract is now available which prevents the adrenal cortex atrophy in the hypophysectomized organism and stimulates the cortical tissue in normal animals.4 It is fairly obvious that the integrity of the adrenal cortex is, therefore, dependent upon the hypophysis. As far as compensatory hypertrophy of the adrenal cortex is concerned, a reasonable hypothesis is as follows. The maintenance of a normal amount of adrenal cortex tissue is dependent upon the concentration of adrenal cortex hormone circulating in the organism. When one adrenal is removed, the adrenal cortex secretion is reduced and the stimulation received by the other gland ...