Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.
 ...
PMID:Occult Cushing's syndrome in type-2 diabetes. 1467 Nov 73

We assessed the value of midnight salivary cortisol for the initial diagnosis of Cushing's syndrome. Sixty-three patients with various causes of Cushing's syndrome (37 with Cushing's disease, 17 with adrenal Cushing's syndrome, and nine with ectopic ACTH syndrome) and 54 control subjects with simple obesity were studied. All patients with Cushing's syndrome excreted more than 90 microg urinary free cortisol (UFC)/d (248 nmol/d), and all controls excreted less than 90 microg/d UFC. All patients with Cushing's syndrome had a midnight salivary cortisol concentration above 2.0 ng/ml (5.52 nmol/liter), whereas only three controls did so [2.0 ng/ml (5.52 nmol/liter); 2.05 ng/ml (5.66 nmol/liter); and 3.6 ng/ml (9.96 nmol/liter)]. This cut-off provides a sensitivity of 100% and a specificity of 96%. In patients with Cushing's syndrome, midnight salivary cortisol concentrations were correlated with UFC collected over the same period of time (0800-0800 h). Salivary cortisol measurements taken every 4 h showed a typical lack of circadian variation. The daily measurement of midnight salivary cortisol concentrations for 2 wk or more in five other out-patients (with obvious Cushing's disease, subclinical adrenal Cushing's syndrome, suspected Cushing's syndrome, pituitary incidentaloma, and prolactinoma) demonstrated the clinical utility of this factor. Measuring midnight salivary cortisol is an easy and noninvasive means of diagnosing hypercortisolism. Its diagnostic accuracy is identical to, if not better than, that of previously described gold standards.
 ...
PMID:Midnight salivary cortisol for the initial diagnosis of Cushing's syndrome of various causes. 1524 Jun 13

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders.
 ...
PMID:Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders. 1552 86

Untreated Cushing's disease and the resultant chronically elevated glucocorticoid levels lead to severe metabolic disturbances, including diabetes mellitus, obesity, hypertension, muscle wasting, and osteoporosis. Although transsphenoidal resection has become the standard of care for Cushing's disease with high initial success rates, little information is available on the long-term morbidity and mortality of patients in remission compared with patients with recurrent or persistent Cushing's disease after such treatment. We therefore conducted a retrospective study of 289 patients with Cushing's disease who underwent transsphenoidal microsurgery for an ACTH-secreting adenoma at a tertiary care center exclusively by one surgeon (C.B.W.). Postoperative remission was achieved in 82% (n = 236) of patients, with best initial remission rates observed in patients with grade I (86%) and II (83%) or stage 0 (88%), A (94%), and B (100%) tumors. Male gender, larger tumor size, and higher stage predicted poorer initial outcome. Long-term follow-up was obtained on 178 patients, with a median follow-up time of 11.1 yr (range, 0.6-24.1 yr). Thirteen of 150 (9%) of patients in initial remission developed recurrent disease, and 12 patients underwent additional treatment. At last follow-up, only two of these patients had active disease. However, of the 28 patients with initial persistent disease who had follow-up greater than 6 months, 10 patients continued to have active disease at last follow-up. Although overall survival rates in patients with initial remission did not differ significantly from expected compared with the general population based on age and sex distribution, patients with initial persistent disease had a significant increase in mortality compared with the expected mortality. Thus, successful treatment of Cushing's disease is associated with normal long-term survival. These results suggest that patients with persistent Cushing's disease require early and aggressive intervention to attempt to prevent this excess mortality.
 ...
PMID:Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. 1557 2

The development of Cushing's disease among patients with deficiency of 21-hydroxylase has not been observed to date. The clinical manifestations and the hormonal profile of this exceptional association are herein described through the study of two cases. The first one was a 39-yr-old woman who had undergone non-curative transsphenoidal surgery for a pituitary-dependent Cushing's syndrome 12 yr before. She showed hypertension, central obesity, severe hirsutism, alopecia and hyperpigmentation. Urinary excretion of cortisol was normal, but ACTH levels were very high and hormonal dynamic studies (cortisol circadian rhythm, insulin-induced hypoglycemia and dexamethasone suppression tests) revealed the qualitative disturbances that characterize Cushing's disease. Serum concentrations of androstenedione, free testosterone and 17-hydroxyprogesterone were clearly increased. Reexamination of the tissue samples from previous surgery confirmed the presence of an ACTH-producing pituitary adenoma. CYP21 gene analysis found the splicing 655G mutation at intron 2 and the V281L mutation at exon 7. The second case was a 21-yr-old woman who was diagnosed with pituitary ACTH-dependent Cushing's syndrome according to unequivocal clinical and laboratory findings. However, hirsutism was particularly severe and both serum androgens and 17-hydroxyprogesterone were elevated. The patient was heterozygote for a large conversion of CYP21 gene. In these cases, the clinical and biochemical expression of Cushing's syndrome was determined by the different severity of 21-hydroxylase deficiency and the subsequent residual ability of adrenal cortex to synthesize cortisol.
 ...
PMID:Clinical manifestations and hormonal profile of two women with Cushing's disease and mild deficiency of 21-hydroxylase. 1571 59

While depression is common in Cushing's syndrome from whatever cause (pituitary, adrenal, or ectopic adrenocorticotropic hormone-secreting tumor or hyperplasia, or exogenous administration of glucocorticoids) and hypercortisolemia is prevalent in major depression, any association between seasonal affective disorder and Cushing's syndrome is unknown. We present a case of seasonal bipolar disorder, gradually worsening for more than 9 years (1985-1994), accompanied by increasing osteoporosis, mild weight gain, and slight truncal obesity in a middle-aged woman. In January 1991, her seasonal affective disorder was successfully treated with light therapy, but in the following year, bipolar mood swings with a seasonal pattern emerged, which were refractory to light therapy and antidepressants but responsive to lithium. In August 1992, she became depressed despite a 1500-mg lithium daily dosage along with light therapy, and, in 1993, a diagnosis of Cushing's disease (Cushing's syndrome as a result of a pituitary adrenocorticotropic hormone-secreting tumor) was made. The pituitary tumor was removed in February 1994, and pituitary function was fully restored by 1996. While the symptoms of Cushing's syndrome subsided, her bipolar illness continued to require maintenance treatment with low doses of lithium but did not require light therapy.
 ...
PMID:A case of seasonal bipolar disorder exacerbated by Cushing's disease. 1572 34

The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.
 ...
PMID:Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma. 1575 38

Cushing's syndrome comprises the symptoms and signs associated with prolonged exposure to inappropriately elevated levels of free plasma glucocorticoids. When iatrogenic causes are excluded, the commonest cause of Cushing's syndrome is Cushing's disease, accounting for approximately 70% of cases. We present the case of a 20-year-old male patient with central obesity, moon face and purple-red striae, whose diagnostic investigation shows a pituitary macroadenoma. The patient was submitted to transsphenoidal hypophysectomy, but developed early recurrence. He was submitted to a second transsphenoidal intervention followed by pituitary radiation. Presently, the patient is in clinical and laboratory remission.
 ...
PMID:[Cushing's disease caused by pituitary macroadenoma]. 1576 68

Craniopharyngioma is a common sellar region tumor occurring in children. It usually manifests as endocrinological deficits such as short stature, delayed puberty, and obesity. Patients with craniopharyngioma commonly present with visual deficits and hydrocephalus. The authors present the case of a child who presented with short stature and clinical evidence of Cushing disease (CD) associated with a suprasellar tumor. The patient underwent insertion of an Ommaya reservoir into the tumor's cystic portion. High adrenocorticotropic hormone (ACTH) levels were demonstrated within the cyst's fluid and in the serum. After adequate decompression of the tumor, the patient underwent total resection. The tumor pathology was compatible with an adamantinomatous craniopharyngioma and immunohistochemical studies failed to show staining for ACTH. Panhypopituitarism developed postoperatively in the patient and he received hormone substitution therapy with final adequate height and normal-high weight. The neurosurgical implications of CD along with a possible mechanism for this patient's presentation are discussed in detail on the basis of the pertinent literature.
 ...
PMID:Craniopharyngioma and Cushing disease: case report. 1588 59

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1 and 11beta-HSD2) catalyse the interconversion of hormonally active cortisol and inactive cortisone. The enzyme evolved from a metabolic pathway to a novel mechanism underpinning human disease with the elucidation of the role of the type 2 or 'kidney' isozyme and an inherited form of hypertension, 'apparent mineralocorticoid excess'. 'Cushing's disease of the kidney' arises because of a failure of 11beta-HSD2 to inactivate cortisol to cortisone resulting in cortisol-induced mineralocorticoid excess.Conversely, 11beta-HSD1 has been linked to human obesity and insulin resistance, but also to other diseases in which glucocorticoids have historically been implicated (osteoporosis, glaucoma). Here, the activation of cortisol from cortisone facilitates glucocorticoid hormone action at an autocrine level. The molecular basis for the putative human 11beta-HSD1 'knockout'--'cortisone reductase deficiency'--has recently been described, an observation that also answers a long standing conundrum relating to the set-point of 11beta-HSD1 activity. In each case, these clinical studies have been underpinned by studies in vitro and the manipulation of enzyme expression in vivo using recombinant mouse models.
 ...
PMID:11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. 1607 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>