Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm 3 respectively; P < 0:0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1:5 Ϯ 0:8 years and 0%) than in those with a macroadenoma (0:7 Ϯ 0:6 years and 40%; P < 0:05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134 Ϯ 78 and 130 Ϯ 7 ng/l respectively) than in those with microadenoma (52 Ϯ 28 and 56 Ϯ 19 ng/l, P < 0:05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3:4 Ϯ 0:3 mmol/l and 1273 Ϯ 401 lymphocytes/mm 3 ) than in those with microadenoma (3:8 Ϯ 0:3 mmol/l and 1852Ϯ668 lymphocytes/mm 3 ; P < 0:05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28 Ϯ 24%, compared with 62 Ϯ 39% in those with microadenoma; P < 0:05), less suppression of plasma cortisol by high doses of dexamethasone (¹30 Ϯ 14%, compared with ¹61 Ϯ 25%; P < 0:05), and a reduced concentration ratio of mean basal cortisol to ACTH (7 Ϯ 3, compared with 12 Ϯ 5; P < 0:05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0:4 Ϯ 0:2 × 10 3 IU/l and 2:3 Ϯ 1:8 mIU/l, compared with 1:8 Ϯ 0:6 × 10 3 IU/l and 5:2 Ϯ 1:6 mUI/l; P < 0:05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions. European Journal of Endocrinology 138 153-159
We studied plasma atrial natriuretic peptide (ANP) concentrations in seven normal subjects after the acute intravenous infusion of sodium chloride/potassium chloride solution (saline). Three separate infusions of 6, 12 and 18 ml of saline/kg body weight each significantly increased the circulating concentration of ANP without changes of plasma osmolality or electrolyte concentrations. The mean maximal rise of the plasma ANP concentration after the three saline infusions was significantly correlated (r = 0.74, P less than 0.001) with, but occurred 10-30 min later than, the maximal atrial pressure rise. These observations are in accord with the hypotheses that: (a) ANP is a circulating natriuretic factor; (b) atrial distension is an important stimulus to ANP release in man.
To assess the relationship between cardiac and extra-cardiac dysfunction in diabetic autonomic neuropathy, the gastric acid output and the pancreatic polypeptide (hPP) secretion in response to sham feeding were evaluated in diabetic patients with (group 1) and without (group 2) cardiac autonomic neuropathy (CAN), and in normal subjects (group 3). All patients assigned to the group with CAN exhibited an impaired beat-to-beat heart rate variation during deep breathing. The basal gastric acid output was comparable in the three groups (1.3 +/- 0.5, 2.8 +/- 1.5, and 3.9 +/- 1.5 mmol/h, respectively). In contrast, the gastric acid output stimulated by sham feeding was significantly lower in patients with CAN (5.3 +/- 1.3 mmol/h) than in diabetic subjects without CAN (14.0 +/- 3.5 mmol/h; P less than 0.01) and in controls (10.9 +/- 3.1; P less than 0.05). The maximal gastric acid secretion capacity, determined after pentagastrin injection, was similar in all patients. Mean basal hPP concentrations were comparable in the three groups (185 +/- 53 pg/ml, 131 +/- 29 pg/ml, and 116 +/- 19 pg/ml). In the controls and diabetic subjects without CAN, a significant mean 60% increase of the hPP levels above basal values was observed during sham feeding. In contrast, no significant hPP response occurred in the group with CAN. These data suggest that diabetic CAN is associated with dysfunctions of the vagal pathways controlling the gastric acid output and the hPP secretion. Moreover, the results demonstrate a strong association between cardiac autonomic neuropathy and gastric vagal neuropathy (P less than 0.001).
ET-1 and ETAR overexpression observed in thyroid carcinoma suggest a mitogenic role of ET-1 that theoretically could be countered by ETAR antagonists. ET-1 and ETAR overexpression in thyroiditis supports a role of ET-1 in the inflammatory process.
The administration of exogenous atrial natriuretic peptide (ANP) causes a natriuresis and diuresis in man, but this has, to date, only been demonstrated at plasma ANP concentrations within the high pathological or pharmacological ranges. Evidence that ANP acts physiologically requires the demonstration of a natriuretic effect when it is infused to recreate plasma concentrations similar to those observed after physiological stimuli. We infused human alpha-ANP (1-28) at a calculated rate of 1.2 pmol min-1 kg-1 for 3 h into seven water-loaded normal subjects, achieving plasma ANP concentrations within the upper part of the physiological range. The subjects' resting plasma ANP concentration increased from 3.8 +/- 1.5 to 20.9 +/- 1.9 pmol/l. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 +/- 18 to 182 +/- 30 mumol/min (P less than 0.001) and a 28% increase of mean water excretion from 10.8 +/- 0.8 to 13.8 +/- 1.6 ml/min (P less than 0.01). The infusion suppressed mean plasma renin activity from 1.55 +/- 0.10 to 1.17 +/- 0.06 pmol of ANG I h-1 ml-1 (P less than 0.001). Mean plasma aldosterone concentration (242 +/- 16 basally and 215 +/- 15 pmol/l at the end of ANP infusion) did not change significantly. Pulse rate and blood pressure were unchanged throughout the study. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day.(ABSTRACT TRUNCATED AT 250 WORDS)
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