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

Ectopic ACTH syndrome is a clinicopathologic condition produced by certain tumors which release hormone that is indistinguishable from ACTH. It orginates the chemical and clinical anomalies characteristic of Cushing's syndrome by its action on the adrenal glands. The tumors may be present in any organ, though they are most frequently found in the lungs, thymus, pancreas or gastrointestinal tract. They may be benign or malignant, though usually the latter. Secretion of the hormone is completely autnomous; it is release in a way similar to that of the hypophysis. Not infrequently other hormones besides ACTH are also produced, such as MSH, serotonin, and CRF. Ectopic ACTH is of higher molecular weight than hypophyseal ACTH, which suggest it may be comprised of the latter bounded covalently to a peptide. The clinical course is rapid, so that not all of the symptoms of Cushing's syndrome develop. Moon face, osteoporosis, and obesity are typically lacking; melanodermia and hypokalemic alkalosis ofter appear. Laboratory data include an increase in ACTH and cholesterol concentrations, disappearance of the nictameral rhythm, and an increase in urinary excretion of 17-hydroxycorticoids and 17-ketosteroids. Stimulation and supression tests are abnormal. The prognosis is poor and the only possible treatment is a complete surgical removal of the tumor. Irradiation or chemotherapy could be applied as well as the correction of the adrenal hyperfunction by the administration of drugs or by total bilateral adrenalectomy.
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PMID:[Ectopic ACTH syndrome (author's transl)]. 22 77

A 69-year-old female patient had been treated with glucocorticoid for eight years because of rheumatoid arthritis. She showed characteristic Cushingoid features such as central obesity, moon face, and fragility of skin and vessels. She was disabled because of spinal compression fracture and muscle weakness. The blood pressure was 186/100 mmHg and the laboratory tests revealed serum K: 2.8 mEq/l, WBC: 15, 510/mm3, total cholesterol: 310 mg/dl. These suggested that she had iatrogenic Cushing's syndrome. After discontinuation of glucocorticoid, however, the serum cortisol level remained high. This fact prompted us to conduct further examinations for Cushing's syndrome. Oral dexamethasone administration did not suppress the plasma cortisol level and a left adrenal adenoma was found on abdominal CT scan. Because of the presence of bleeding diathesis, operation for adenoma was contraindicated. Though we tried to treat her with metyrapone, trilostane or opeprim (OP'-DDD), we had to abandon specific treatment because of severe side effects such as acute adrenal dysfunction and gastrointestinal problems. Decrease in the endogenous cortisol level after metyrapone treatment caused exacerbation of symptoms of rheumatoid arthritis. This is a peculiar case in which the long-term administration of glucocorticoid for rheumatoid arthritis might have concealed Cushing's syndrome, and conversely the increased intrinsic adrenal steroid hormone might have suppressed the activity of the rheumatoid arthritis.
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PMID:[Cushing's syndrome found during long-term glucocorticoid treatment of rheumatoid arthritis in an elderly woman]. 156 Jun 10

A 42-year-old female was admitted to our hospital with a chief complaint of hypertension. Endocrinologically, the plasma cortisol level was increased, but its diurnal rhythm had disappeared and the plasma cortisol level was not suppressed by dexamethasone loading at 2 mg or 8 mg. The plasma ACTH level was low. Computerized tomographic scan, echography and adrenocortical scintigraphy showed an adrenocortical tumor on the right adrenal gland. Physical examination did not reveal typical Cushingoid symptoms such as moon face, central obesity and violaceous striae. Thus we diagnosed this case as non-Cushingoid Cushing's syndrome and performed right adrenalectomy. Histological examination showed adreno-cortical adenoma without malignancy.
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PMID:[A case of non-Cushingoid Cushing's syndrome]. 196 57

Young and mature, genetically obese and non-obese, spontaneously hypertensive rats (SHR) were injected with saline (controls) or naloxone for 12 weeks. Naloxone stilled the hyperphagia to a normal intake in the obese SHR (Obese/SHR) so that young Obese/SHR did not develop their usual massive obesity and mature Obese/SHR that had become massively obese were reduced to leanness. The naloxone-treated young, obese and non-obese SHR (controls) exhibited marked reduction of the weight of their pituitary and adrenal glands, whereas the pituitary and adrenal glands of naloxone-treated mature, obese and non-obese/SHR were greatly increased in weight. The elevated systolic blood pressure of the obese and non-obese rats was reduced after chronic treatment with naloxone. Naloxone treatment caused reduction of blood ACTH, corticosterone, and beta endorphin levels but elevated growth hormone levels. The characteristic hyperinsulinemia, hyperlipidemia, hyperglycemia, elevated BUN levels, and the Cushingoid spectrum of degenerative changes found in Obese/SHR did not appear in naloxone-treated rats.
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PMID:Anti-opiate (naloxone) suppression of Cushingoid degenerative changes in obese/SHR. 299 79

Male, 5 months old, massively obese, spontaneously hypertensive rats (Obese/SHR) were given 10 mg alloxan/100 g b.w., s.c., to induce diabetes. Control Obese and non-obese/SHR were given saline. Insulin therapy was withheld. All of the animals were killed at 6 months of age. Alloxan caused a slight but statistically significant increase in blood pressure, pituitary and adrenal glandular hyperplasia, hyperlipidemia, hyperglycemia, and increased BUN levels. The giant sized islets of Langerhans in Obese/SHR showed only partial degranulation of the insulin-producing beta cells concomitant with residual but apparently adequate blood insulin levels, whereas the islets of non-obese/SHR exhibited virtually total beta cell degranulation and only trace amounts of blood insulin. The alloxanized, non-obese rats were severely emaciated; the alloxanized Obese/SHR maintained their obesity. Alloxan-treated, Obese and non-obese/SHR manifested gross and microscopic degenerative changes suggesting acceleration of the normal aging process. The genetically-programmed pathogenesis of diabetes, obesity, hypertension, and Cushingoid pathophysiology of Obese/SHR may be due to hyperadrenocorticism.
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PMID:Resistance of obese and non-obese, spontaneously hypertensive rats to alloxan-induced diabetes. 635 Jul 80

Male and female, massively obese and nonobese, spontaneously hypertensive rat (SHR) which are hypersensitive to stress were kept under quiescent conditions; they were autopsied at 15 months of age. The blood pressure of the Obese/SHR plateaued at 166 mmHg versus 198 mmHg for the nonobese/SHR. The once massive thymi vanished in the Obese/SHR accompanied by greatly enlarged adrenal glands, pituitary basophilia, greatly elevated levels of adrenocorticotrophin, corticosterone, deoxycorticosterone, aldosterone, fatty liver, hyperlipidemia, and hyperglycemia. The Obese/SHR were hyperadrenocorticoid compared with their nonobese siblings and manifested a Cushingoid spectrum of degenerative changes (e.g., thin skin, hypertension, diabetes, kidney stones, and accelerated aging). The provision of a nonstressful environment is believed to have dampened the usual chronic hyperadrenocorticism and prolonged the lifespan of the Obese/SHR.
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PMID:Cushingoid pathophysiology of old, massively obese, spontaneously hypertensive rats (SHR). 682 32

Leukemia inhibitory factor (LIF) regulates the mature hypothalamic-pituitary-adrenal axis in vivo. In vitro, LIF determines corticotroph cell proliferation and induces POMC transcription. To explore LIF action on pituitary development, transgenic mice expressing LIF driven by the pituitary glycoprotein hormone alpha-subunit (alphaGSU) promoter were generated. Transgenic mice exhibited dwarfism with low IGF-I (29 +/- 9 ng/ml vs. wild type (WT) 137 +/- 16 ng/ml; P < 0.001), hypogonadism with low FSH (0.04 +/- 0.023 ng/ml vs. WT 0.63 +/- 0.18 ng/ml; P < 0.001), and Cushingoid features of thin skin and truncal obesity with elevated cortisol levels (86 +/- 22 ng/ml vs. WT 50 +/- 14 ng/ml; P = 0.002). Their pituitary glands showed corticotroph hyperplasia, striking somatotroph and gonadotroph hypoplasia, and multiple Rathke-like cysts lined by ciliated cells. LIF, overexpressed in Rathke's pouch at embryonal day 10, diverts the differentiation stream of hormone-secreting cells toward the corticotroph lineage and ciliated nasopharyngeal-like epithelium. Thus, inappropriate expression of LIF, a neuro-immune interfacing cytokine, plays a key role in the terminal differentiation events of pituitary development and mature pituitary function.
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PMID:Pituitary-directed leukemia inhibitory factor transgene causes Cushing's syndrome: neuro-immune-endocrine modulation of pituitary development. 981 97

A girl who developed Cushingoid features in peripuberty, but was eucortisolemic, was previously reported to have markedly elevated lymphocyte glucocorticoid receptor sites per cell with normal binding affinity as a potential cause of her phenotype. Her circadian rhythm of cortisol and pituitary-adrenal axis were initially intact, but later proved to be dysregulated. The patient presented at age 10.8 yr with centripetal obesity, moon facies, buffalo hump, and purple striae, but no statural stunting, which is a cardinal sign of Cushing's syndrome. At 11.5 yr she suffered a compression fracture of the L1 vertebra. That prompted treatment with the antiprogestin drug mifepristone (RU486), which was administered at high dose to achieve an antiglucocorticoid effect. From ages 13.75 yr through 15.5 yr, RU486 was administered in various intervals to suppress her Cushingoid features. Once RU486 was introduced, however, a consistent correlation over time between the Cushingoid features and glucocorticoid receptor sites per cell was no longer observed. However, the number of glucocorticoid receptor sites per cell tended to decrease in response to administering RU486. Ultimately, her Cushingoid phenotype proved to be transient.
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PMID:Normocortisolemic Cushing's syndrome initially presenting with increased glucocorticoid receptor numbers. 1063 57

Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone. However, no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas. They represent an interesting model for studying GH secretion, as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign. In the present study, 10 patients (3 men and 7 women, aged 48-63 yr) with an adrenal mass discovered serendipitously underwent, on separate occasions, a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist, arginine. Thirteen age-matched healthy volunteers served as controls. Briefly, arginine (30 g) was infused from -30 to 0 min, and GHRH (100 microg) was injected as a bolus at 0 min, with measurement of serum GH [immunoradiometric assay (IRMA)] every 15 min for 150 min. Plasma IGF-I (RIA after acid-ethanol extraction) was measured in a morning sample. The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy. Patients with obesity and/or diabetes were excluded. The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [urinary free cortisol (UFC) excretion, serum cortisol at 0800 h, plasma ACTH at 0800 h, morning cortisol after overnight 1 mg dexamethasone]. Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis, including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1; the fifth patient displayed low ACTH and resistance to dexamethasone suppression. However, all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland. As a group, the patients displayed greater UFC excretion and lower ACTH concentrations than the controls. GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls (GH peak, 5.7 +/- 5.2 vs. 18.0 +/- 7.0 microg/L; P < 0.0001), whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups (GH peak, 33.5 +/- 20.3 vs. 33.7 +/- 17.5 microg/L; P = NS). The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls (751 +/- 531% vs. 81 +/- 45%; P = 0.0001). Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups. In summary, the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone, as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine. The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma.
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PMID:Growth hormone (GH) responses to GH-releasing hormone alone or combined with arginine in patients with adrenal incidentaloma: evidence for enhanced somatostatinergic tone. 1072 81

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.
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PMID:A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome. 1187 66


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