Cushing's disease.

D C Aron; J W Findling; J B Tyrrell

Home/Archive/PubMed

PubMed · 2826137

Cushing's disease.

D C Aron·J W Findling·J B Tyrrell

View original source ↗Export metadata ↓

Abstract

Cushing's disease is a form of Cushing's syndrome, persistent inappropriate hypercortisolism, that results from pituitary ACTH hypersecretion. It currently accounts for 70 per cent of adult cases of Cushing's syndrome and affects mainly women of childbearing age. The pathology, cause, and clinical and laboratory features of the disease are discussed. The initial step in diagnosis is documentation of endogenous hypercortisolism, which is followed by identification of the cause. Selective transsphenoidal resection of ACTH-producing pituitary adenomas is the initial treatment of choice. The roles of radiotherapy and medical therapy are discussed.

Explore related subjects

Adrenalectomy Adrenocorticotropic Hormone Cushing Syndrome Diagnosis, Differential Humans Nelson Syndrome Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

D C Aron, J W Findling, J B Tyrrell. 1987. Cushing's disease.. https://pubmed.ncbi.nlm.nih.gov/2826137/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Region-specific expression and sex-steroidal regulation on aromatase and its mRNA in the male rat brain: immunohistochemical and in situ hybridization analyses.

The brain has an estrogen-biosynthetic potential resulting from the presence of neuronal aromatase, which controls the intraneural sex-steroidal milieu and is involved in brain sexual differentiation, psychobehavioral regulation, and neuroprotection. In the rat brain, three distinct aromatase-P450-immunoreactive (AromP450-I) neural groups have been categorized in terms of their peak expression time (fetal, fetoneonatal, and young-to-adult groups), suggesting the presence of region-specific regulation on brain AromP450. In the present study, we compared the expressions between AromP450 protein and mRNA by using immunohistochemistry and in situ hybridization with an ovary-derived cRNA probe in serial sections of fetal, fetoneonatal, and adult male rat brains and then performed steroidal manipulations to evaluate the sex-steroidal effects on AromP450 in adult orchiectomized and adrenalectomized (OCX + ADX) male rats. As a result, prominent mRNA signals were detected in the fetal (i.e., the anterior medial preoptic nucleus) and fetoneonatal (i.e., the medial preopticoamygdaloid neuronal arc) groups, although no detectable signal was found in the "young-to-adult" group (i.e., the central amygdaloid nucleus). In addition, the "fetoneonatal" AromP450-I neurons were prominently reduced in number and intensity after OCX + ADX and then were reinstated by the administration of dihydrotestosterone, testosterone, or 17beta-estradiol. In contrast, none of the sex steroids had any significant effects on the young-to-adult group. Several possible explanations were explored for why the young-to-adult group may differ in aromatase expression and regulation, including the possibility that distinct splicing variants or isozymes for aromatase exist in the rat brain.

Adrenalectomy↗

PubMed2007

Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial memory deficits that are not reversed by chronic treatment with corticosterone or fluoxetine.

Long-term adrenalectomy (ADX) causes a nearly complete and selective loss of granule cells in the dentate gyrus (DG) of the hippocampus. Previously, learning and memory deficits have been observed following ADX-induced granule cell degeneration for tasks that require the hippocampus. Our objective here was to determine whether corticosterone (CORT) replacement and treatment with the neurogenic compound fluoxetine could reverse behavioral deficits after ADX. We trained ADX and control rats in a moving, hidden platform version of the Morris water task before chronic administration (6 weeks) of CORT and either fluoxetine or vehicle. After treatment, all rats were retested in the Morris water task. Brains were labeled for the endogenous neurogenic markers Ki67 and doublecortin. Here we provide evidence that neurogenesis persists at a normal rate in the hippocampus after long-term ADX. After 8 weeks of CORT and fluoxetine administration, ADX-fluoxetine rats did not differ significantly compared to ADX-vehicle rats receiving CORT or compared to control rats in the number of Ki67 or doublecortin labeled cells. ADX-fluoxetine rats also did not significantly differ from ADX-vehicle rats in regards to granule cell layer thickness. Our results indicate that long-term ADX is associated with impaired spatial ability in the Morris water task and that neither chronic treatment with CORT, nor with CORT and fluoxetine are capable of altering the Morris water task deficit.

Adrenalectomy↗

PubMed2007

Dissociation between apoptosis, neurogenesis, and synaptic potentiation in the dentate gyrus of adrenalectomized rats.

Removal of adrenal hormone corticosterone in rats aged 3-4 months results within 3 days in acceleration of apoptosis and proliferation of newborn cells in the dentate gyrus (DG). A critical question is whether such a shift in the maturity of dentate cells after adrenalectomy (ADX) affects synaptic plasticity. To address this question, male rats were adrenalectomized and synaptic potentiation was recorded in vitro in hippocampal slices, as well as in vivo, in response to high frequency stimulation of the perforant path, 3 days after ADX. At this time-point, cell loss was assessed and proliferation was examined. Based on two independent parameters, bromodeoxyuridine and Ki-67, we found that removal of the adrenal glands increases proliferation rate. This increase in proliferation was, in particular, evident in those animals that displayed substantial cell loss. The accelerated cell-turnover after ADX was accompanied by reduced synaptic potentiation, both when recorded in vitro and in vivo. Corticosterone replacement in vivo (in adrenalectomized animals), at levels that activate the mineralocorticoid receptor, prevented ADX-induced proliferation, apoptosis, and restored synaptic potentiation to control levels. Importantly, corticosterone applied to slices from adrenalectomized rats also normalized synaptic potentiation, despite increased proliferation. This suggests that changes in cell proliferation and apoptotic cell death in the DG are not necessarily key factors determining the efficacy of synaptic potentiation.

Adrenalectomy↗