Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation.
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PMID:Bartter's syndrome--case report. 15 51

A 29-year-old man had a six-month history of fatigue and hypokalemia. Gastrointestinal losses of potassium were not judged significant. The patient denied ingestion of licorice, large quantities of laxatives, or diuretics. Clinical and laboratory findings were consistent with Bartter's syndrome in the adult. Normal blood pressure, hypokalemic alkalosis, and hyperaldosteronism, with insensitivity to the pressor effect of angiotensin infusion, were present. Another major finding in Bartter's syndrome, juxtaglomerular hyperplasia, was not demonstrated because plans for renal biopsy were cancelled when thiazide was detected in the urine, utilizing chemical extraction and spectrophotometry. Surreptitious ingestion of diuretics must be excluded in any adult patient in whom a diagnosis of Bartter's syndrome is considered.
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PMID:Factitious Bartter's syndrome. 90 Oct 95

Familial glucocorticoid resistance (FGR) is a rare hereditary disorder characterized by hypercortisolism and the absence of stigmata of Cushing's syndrome. The inability of glucocorticoids to exert their effects on target tissues is compensated for by increases in circulating corticotropin (ACTH) and cortisol, the former causing excess secretion of both adrenal androgens and adrenal steroid-biosynthesis intermediates with salt-retaining activity. There is considerable variability in the clinical presentations of FGR ranging from asymptomatic, to isolated chronic fatigue and to hypertension with or without hypokalemic alkalosis or to hyperandrogenism, or both. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men it may lead to infertility and in children to precocious puberty. The reported molecular defects in FGR, such as point mutations and a microdeletion of the glucocorticoid receptor (GR) gene, cause partial resistance by, respectively, compromising the function of the GR or decreasing its intracellular concentration in glucocorticoid target tissues. Complete glucocorticoid resistance is believed to be incompatible with life in humans. Hence, the glucocorticoid resistance cases reported have been partial and of variable degree. The extreme variability in the clinical manifestations of the disorder can, additionally, be explained by differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps by different biochemical defects of the glucocorticoid receptor, causing selective resistance of certain glucocorticoid responses in specific tissues. Isolated tissue-resistance from a somatic mutation of the GR in a corticotropinoma from a patient with Nelson's syndrome was also found, suggesting that this may be a mechanism of tumorigenesis. There is additional evidence that defects of GR function can appear surreptitiously in a variety of clinical conditions, suggesting that glucocorticoid resistance in humans may be involved in the pathogenesis and/or clinical picture of a plethora of disease states, of which FGR is the archetype.
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PMID:Glucocorticosteroid resistance in humans. Elucidation of the molecular mechanisms and implications for pathophysiology. 782 90

We report on diagnostic and differential diagnostic considerations in the case of a 30 year old Italian woman with hypokalemic alkalosis, fatigue and muscular weakness. The symptoms were caused by a Bartter syndrome with distinctly increased renin but almost normal aldosterone levels in the serum and increased aldosterone values in the urine.
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PMID:[Hypokalemia in the course of a Bartter syndrome]. 801

Glucocorticoid resistance results from the partial, albeit apparently generalized, inability of glucocorticoids to exert their effects on target tissues. The condition is associated with compensatory increases in circulating pituitary corticotropin and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from chronic fatigue (perhaps a result of glucocorticoid deficiency in the central nervous system) to various degrees of hypertension with or without hypokalemic alkalosis or hyperandrogenism, or both, caused by increased cortisol and other salt-retaining steroids and adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility and in children, to precocious puberty. Different molecular defects, such as point mutations or a microdeletion of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and appear to cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by the overall degree of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor, with selective resistance of certain glucocorticoid responses in specific tissues. The various different symptoms of classic glucocorticoid resistance and the theoretical potential of this condition to appear surreptitiously emphasize the importance of the glucocorticoid receptor in the pathogenesis of human disease.
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PMID:Syndromes of glucocorticoid resistance. 818 39