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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cushing's syndrome invariably presents with a classical phenotype comprising central adiposity, prominence of dorsal, supraclavicular and temporal fat pads, bruising, abdominal striae, proximal myopathy, and hypertension. We report the case of a 20-yr-old student with pituitary-dependent Cushing's syndrome who was spared this classical phenotype because of a defect in the peripheral conversion of cortisone to cortisol. She presented to her general practitioner with secondary amenorrhea. Clinical examination revealed normal fat distribution (body mass index, 20.9 kg/m(2)), absence of hirsutism, myopathy, or bruising; her blood pressure ranged from 115/70 to 122/82 mm Hg. She was investigated for biochemical hypercortisolemia because of a mildly elevated random circulating cortisol (serum cortisol, 661 nmol/liter). Cushing's syndrome was confirmed on the basis of repeatedly elevated urinary free cortisols (831-1049; reference range, <350 nmol/24 h), failure of low-dose dexamethasone suppression (611 nmol/liter) and loss of circadian cortisol secretion. Investigations suggested Cushing's disease; there was suppression after high-dose dexamethasone (<20 nmol/liter) and a 950% increase in ACTH after stimulation with CRH. Pituitary magnetic resonance imaging revealed a 3-mm adenoma within the pituitary gland. Urinary corticosteroid metabolites were analyzed by gas chromatography-mass spectrometry and demonstrated a decreased THF+allo-THF/THE ratio of 0.66 (mean +/- SE in Cushing's disease, 1.74 +/- 0.24) suggesting a defect in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), an enzyme that converts the inactive glucocorticoid cortisone to active cortisol. Transphenoidal microadenomectomy was performed, and histology confirmed the diagnosis of a corticotroph adenoma. Postoperatively, serum cortisol was undetectable and replacement therapy was commenced. Subsequent investigations revealed a significantly impaired ability to convert an oral dose of cortisone acetate (25 mg) to cortisol, reduced serum cortisol to cortisone ratios, and a reduced serum half-life for cortisol (57.3 min). These results provide strong evidence for a partial defect in 11beta-HSD1 activity and concomitant increase in cortisol clearance rate. We have described a case of Cushing's disease that failed to present with a classical phenotype, and we postulate that this is due to a partial defect of 11beta-HSD1 activity, the defect in cortisone to cortisol conversion increasing cortisol clearance and thus protecting the patient from the effects of cortisol excess. This observation may help to explain individual susceptibility to the adverse effects of glucocorticoids.
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PMID:Absence of Cushingoid phenotype in a patient with Cushing's disease due to defective cortisone to cortisol conversion. 1178 23

This report describes a rare case of ACTH-independent macronodular adrenal hyperplasia (AIMAH) arisen with symptomatic severe hypertension and hypokaliemia. A 55-year-old man was admitted to hospital with a clinical picture characterized by several episodes of transient ischemic attacks (TIA) and right hemiplegia, related to severe arterial hypertension. Laboratory tests showed urinary levels of catecholamines, metanephrines and vanillylmandelic acid (VMA) in normal range; high urinary free cortisol excretion, elevated serum cortisol with loss of the circadian rhythm and low ACTH plasma levels. ACTH failed to respond to CRH administration. Serum cortisol levels were not modified after high doses of dexamethasone. MRI showed bilateral macronodular hyperplasia of adrenal glands, whereas pituitary-MRI did not show tumoral lesions. Therefore, ACTH-independent macronodular hyperplasia was suspected. Though obese, the patient had no typical Cushing habit, and symptomatic hypertension with hypokaliemia was the only clinical evidence for this rare kind of Cushing's syndrome. After obtaining a satisfactory control of blood pressure, the patient was successfully submitted to laparoscopic bilateral adrenalectomy and underwent complete clinical remission. The histology showed adrenal macronodular hyperplasia. During the twenty-four month follow-up, the patient had no further transient ischemic attacks or need of glucocorticoid replacement therapy and withdrew the antihypertensive drugs.
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PMID:A case of severe hypertension caused by ACTH-independent macronodular adrenal hyperplasia. 1193 69

Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder.
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PMID:Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. 1205 88

The diagnosis of Cushing's syndrome rests on the demonstration of clinical features and biochemical abnormalities that reflect hypercortisolism. If a patient presents with typical clinical features such as weight gain with truncal obesity and supraclavicular fat deposition, wide purple striae, and proximal muscle weakness, the diagnosis is clear-cut and is nearly always substantiated by a 24-hour urine free cortisol excretion value more than four times the normal level. However, many patients present with signs and symptoms that are common in the general population, such as hypertension, generalized weight gain, reproductive abnormalities, and depression. Many of these patients have normal cortisol excretion and do not have Cushing's syndrome. Others have mild hypercortisolism caused by psychiatric disorders, obligate exercise, morbid obesity, sleep apnea, or uncontrolled diabetes mellitus. These patients may be confused with those with the true Cushing's syndrome, and thus are considered to have a "pseudo-Cushing" state. Additional observation over time, and testing with midnight cortisol measurements, the 2-day-2-mg dexamethasone suppression test, or the dexamethasone suppression-CRH stimulation test may be useful to identify true Cushing's syndrome in these patients.
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PMID:Diagnostic tests for Cushing's syndrome. 1238 46

Functional activity of hypothalamic-pituitary-adrenocortical axis has been studied under control and restraint stress conditions in rats with inherited stress-sensitive arterial hypertension (ISIAH strain) and in normotensive WAG (Wistar Albino Glaxo) strain. The levels of hypothalamic CRH-mRNA (in control and 2 hrs stress), pituitary and plasma ACTH and plasma corticosterone (in control and after 5, 15 or 30 min of restraint stress), were evaluated. Hypothalamic CRH-mRNA level was found to be approximately the same in the control rats of both strains. In control conditions, the pituitary and plasma ACTH content in ISIAH rats was significantly lower whereas the corticosterone level in the plasma differed from each other in both strain. The restraint stress resulted in a statistically significant increase of the CRH-mRNA in ISIAH rats and not in the WAG rats. Moreover, in spite of the lower ACTH level in stressed ISIAH rats, the corticosterone blood plasma concentration in hypetensive rats was significantly higher. The data obtained confirm the idea that the stress-dependent hypertension might be related to an enhanced sensitivity of the main endocrine links involved in the stress response organization.
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PMID:[Function of hypothalamic-pituitary-adrenocortical system in hypertensive rats of ISIAH strain]. 1258 70

The auditory system is permanently open - even during sleep. Its quick and overshooting excitations caused by noise signals are subcortically connected via the amygdala to the hypothalamic-pituitary-adrenal-axis (HPA-axis). Thus noise causes the release of different stress hormones (e.g. corticotropin releasing hormone: CRH; adrenocorticotropic hormone: ACTH) especially in sleeping persons during the vagotropic night/early morning phase. These effects occur below the waking threshold of noise and are mainly without mental control. Animal experiments show noise-induced changes in sensitivity of cellular cortisol receptors by increase of heat-shock proteins, and ultrastructural changes in the tissue of the heart and the adrenal gland. Increased cortisol levels have been found in humans when exposed to aircraft noise or road traffic noise during sleep. The effects of longer-lasting activation of the HPA-axis, especially long term increase of cortisol, are manifold: immuno suppression (e.g. eosinopenia), insulin resistance (e.g. diabetes), cardiovascular diseases (e.g. hypertension and arteriosclerosis), catabolism (e.g. ostoeporosis), intestinal problems (e.g. stress ulcer) etc. Even worse may be the widespread extrahypothalamical effects of CRH/and/or ACTH which have the potential to influence nearly all regulatory systems, causing for example stress-dysmenorrhea etc. as signs of disturbed hormonal balance.
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PMID:Possible health effects of noise induced cortisol increase. 1268 72

We report a case of Cushing's syndrome due to ACTH-independent macro-nodular adrenal hyperplasia (AIMAH). The patient, a 51-year-old man, had been suffering from poorly controlled arterial hypertension for the previous 6 years and he complained of progressive weight gain, gynecomastia and impotence. Physical examination revealed classic cushingoid features. Endocrine basal assessment showed increased urinary free cortisol (264-600 micrograms/24 hr). Urinary steroid profile showed an increase of total 17-hydroxycorticosteroids (17-OHCS: 23 mg/24 hr), with a threefold increase of tetrahydrocortisol (THF:9.66 mg/24 hr) and of tetrahydrocorticosterone (THB: 1.35 mg/24 hr). Tetrahydrodesossicortisol was only slightly elevated (THS:0.67 mg/24 hr) and tetrahydrodesossicorticosterone was at the inferior limit of the normal range (THDOC: 0.03 mg/24 hr). Total 17-ketosteroids were decreased (17-KS: 3 mg/24 hr). Plasma cortisol level was elevated and without circadian rhythm (26-29 micrograms/dl in the morning, 26-28 micrograms/dl at 24:00 h). DHEAs and free testosterone levels were significantly reduced (106 ng/dl and 3.9 pg/ml respectively). ACTH was undetectable and unresponsive to CRH. Both dexamethasone and octreotide failed to suppress plasma cortisol levels. Abdomen computed tomography scan demonstrated bilaterally enlarged multinodular adrenal glands. Cerebral magnetic resonance revealed no alteration of the pituitary gland. The patient underwent bilateral adrenalectomy. On macroscopic examination, adrenal glands were occupied by multiple yellow nodules and their compressive weight was 190 g, with left adrenal heavier than the right one (120 g and 70 g respectively). Histologically, nodular lesions were predominantly composed of large clear cells, with small foci of "hybrid" cells and adipose tissue metaplasia. Reticularis zone was atrophic. In the immediate post-operatory course pulmonary embolism occurred, despite prophylaxis with low molecular weight heparin. After having recovered from this complication, the patient showed progressive regression of cushingoid status. The findings of increased THF/THS and THB/THDOC ratios were in agreement with a relative hyperfunction of 11-beta-hydroxylase "in vivo", which might have contributed to the hypercortisolism, in addition to the marked increase of secernent adrenal mass.
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PMID:An unusual case of Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia. 1274 99

A 75-year-old woman had tumors in her pituitary, thyroid and left adrenal gland. Plasma ACTH and cortisol levels were both mildly elevated. Both plasma ACTH and cortisol concentrations were partially suppressed by 1 mg of overnight dexamethasone suppression test, while both were inhibited with a dosage of 8 mg dexamethasone. Plasma ACTH and cortisol levels were increased in response to human CRH and desmopressin. Together with the observation of pituitary microadenoma, the patient had a pituitary ACTH-producing tumor. The patient, however, had no typical Cushingoid features, hypertension, or impaired glucose tolerance, suggesting that the tumor had an autonomic ACTH secretion that was insufficient for expressing clinical symptoms, the so-called preclinical Cushing's disease. A case of preclinical Cushing's disease is extremely rare. Further, the patient had thyroid papillary carcinoma and non-functioning adrenal tumor. Molecular genetic analysis demonstrated a polymorphism of the menin gene in the patient. Even without Cushingoid features in pituitary incidentaloma, we concluded that the elevated ACTH and cortisol levels should be followed up by CRH, desmopressin and dexamethasone suppression tests. This patient with preclinical Cushing's disease would be observed whether the physical conditions in the patient develop to overt Cushing's disease.
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PMID:A case of preclinical Cushing's disease, accompanied with thyroid papillary carcinoma and adrenal incidentaloma. 1294 Apr 62

A 56-yr-old woman was referred with a diagnosis of Cushing's disease. Hypertension and severe hypokalemia were present and high urinary free cortisol/cortisone ratio was detected, raising a suspicion of an ectopic ACTH syndrome. Inferior petrosal sinus sampling, thoracic computed tomography, and octreotide scans were negative. Remission and relapse periods lasting 3-4 months were observed during the 3.5 yr of follow-up. Finally a thoracic computed tomography scan showed a basal paracardic nodule in the left lung. After surgery, a well-differentiated neuroendocrine tumor (typical bronchial carcinoid) was diagnosed, staining positively for ACTH. RT-PCR revealed expression of proopiomelanocortin, CRH receptor, and V3 vasopressin receptor. Somatostatin receptor type 1, 2, 3, and 5 mRNA was detected only in tumoral tissue. Interestingly, we observed the simultaneous presence of ghrelin and both GH secretagogue (GHS) receptors (1a and 1b) mRNA in tumoral tissue but not in the normal lung. This finding correlates with the in vivo ACTH hyperresponsiveness to hexarelin (a GHS). This is the first report of a cyclical ectopic ACTH-secreting tumor with an in vivo ACTH response to hexarelin coupled with the tumoral expression of ghrelin and GHS receptors. This finding might imply an autocrine/paracrine modulatory effect of ghrelin in bronchial ACTH-secreting tumors.
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PMID:Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors. 1467 Nov 77

Glycyrrhizic acid (GA) inhibits the activity of 11beta-hydroxysteroid dehydrogenase type 2 in the kidney, with the resulting increase in intrarenal cortisol concentration leading to hypertension and suppression of the renin-aldosterone system. In this paper we describe an interesting case of pseudoaldosteronism, associated with hypocalcemia and an exaggerated ACTH response. A 72-year-old woman was referred to our department for further evaluation of hypokalemia and hypocalcemia. The patient had been taking GA (150 mg/day) for the previous year for treatment of liver damage. Plasma renin activity and aldosterone concentration were both within lower normal limits. Urinary excretion of potassium and calcium was within the upper limit of the normal range and increased with administration of supplements. Plasma ACTH levels increased markedly in response to an intravenous injection of CRH. Cessation of GA and the potassium and calcium supplements on admission, led to a gradual normalization of serum potassium and calcium levels and blood pressure. The hypocalcaemia in our patient was related to decreased tubular reabsorption of calcium as a consequence of renal corticoid excess. It is possible that an increase in the number of CRH receptors in the pituitary following GA treatment caused the exaggerated ACTH response in association with pseudoaldosteronism. The existence of hypocalcemia and an exaggerated ACTH response should be observed carefully when managing pseudoaldosteronism.
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PMID:A case of pseudoaldosteronism, accompanied with hypocalcemia and exaggerated ACTH response. 1500 13


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