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P C Carpenter

Publications and source records attributed to P C Carpenter.

45 records · Page 3Linked to original sources

Increased adrenal sensitivity to angiotensin II in idiopathic hyperaldosteronism.

Plasma aldosterone increases briskly during upright posture in patients with idiopathic hyperaldosteronism, despite only small increases in PRA and presumably small increases in angiotensin II. To examine the postulate that small increments in angiotensin II mediate these brisk increases in aldosterone, we infused graded doses of angiotensin II into normal subjects and patients with idiopathic hyperaldosteronism and compared the changes in levels of plasma aldosterone in the two groups. Supplemental sodium and dexamethasone were given before the infusion to minimize the influence of endogenous angiotensin II and ACTH. In response to the infusion of angiotensin II, increases in the levels of plasma aldosterone of patients with idiopathic hyperaldosteronism were significantly greater than those of normal subjects. In addition, levels of plasma aldosterone increased at a lower rate of infusion of angiotensin II in patients than in normal subjects. It is concluded that patients with idiopathic hyperaldosteronism have increased adrenal sensitivity to angiotensin II. This increased sensitivity may explain the brisk increases in aldosterone that occur during upright posture in these patients.

Adrenal Glands↗

Laboratory medicine. Series on clinical testing. 2. Fractionation of urinary ketosteroids. Procedure and clinical significance.

Ketosteroids, the excretory metabolities of adrenal and gonadal steroids, can be analyzed individually in urine by a simple extraction procedure followed by separation and quantitation by the use of gas/liquid chromatography. The ketosteroids quantitatively detected by the technique are androsterone, etiocholanolone, dehydroepiandrosterone, 11-hydroxyandrosterone, 11-hydroxyetiocholanolone, 11-ketandrosterone, and 11-ketoetiocholanolone. Other steroid metabolities detected are pregnanediol, pregnanetriol, delta5-pregnenetriol, and 11-ketopregnanetriol. In comparison with concentrations of these steroids observed in urine specimens collected from healthy individuals, abnormal results occur in specimens from patients with testicular disease, Cushing's syndrome, adrenal hyperplasia, and several types of female hirsutism. Characteristic profiles for each of these diseases are presented.

11-Hydroxycorticosteroids↗

Transsphenoidal removal of pituitary microadenoma in Cushing's disease.

Twenty-two of 32 patients with Cushing's disease seen at the Mayo Clinic during a 3-year period were carefully studied radiologically (triaxial spiral tomograms of the sella and bilateral carotid arteriograms with magnification and subtraction techniques). Eighteen of these 22 pat-ents had radiologic evidence of small pituitary gland tumors and underwent transsphenoidal microsurgical exploration of the pituitary. A microadenoma (less than 10 mm) was found in 17 of the 18 patients. Hypercortisolism was corrected, and a clinical remission occurred in 16 of the 18 patients; the hypercortisolism persisted in 2 patients. A period of hypocortisolism occurred after removal of the pituitary tumor in all patients who experienced a remission. Remissions have been associated with normal anterior pituitary and adrenocortical function in a large percentage of patients who were adequately studied 6 months or more after pituitary surgery.

Adenoma↗

Isolation, determination of structure and synthesis of the acid-labile conjugate of aldosterone.

1. After administration of 600mg of 3H-labelled aldosterone to human volunteers, 57 mg of homogeneous acid-labile conjugate was isolated from the urine and identified as aldosterone 18 beta-D-glucosiduronic acid. 2. Esterification and acetylation of the conjugate gave a tetra-acetate methyl ester, which, by measurement of the optical rotation and nuclear-magnetic-resonance spectrum, was shown to be a beta-glucosiduronate. This tetra-acetate methyl ester was synthesized in approx. 10% yield by the Koenigs-Knorr procedure. 3. Removal of the acetyl and methyl ester groups from the tetra-acetate methyl ester with alkali was accompanied by almost complete isomerization at C-17 to give 17-isoaldosterone 18 beta-D-glucosiduronic acid. 4. To prevent inversion at C-17 during removal of the acetate and ester groups of beta-glucosiduronate (a) the 3,20-disemicarbazone was prepared, (b) the acetate and ester groups were removed from the disemicarbazone by treatment with alkali, and (c) the semicarbazone groups were removed from the product at pH 2.0, and aldosterone 18 beta-D-glucosiduronic acid was obtained in 47% overall yield. 5. In the presence of components used to synthesize beta-glucosiduronate by the Koenigs-Knorr reaction this substance is converted slowly into the alpha-glucosiduronate; this conversion is responsible, in part, for the low yield of beta-glucosiduronate. 6. Two additional conjugates were obtained in the Koenigs-Knorr reaction; a provisional structure was assigned to one substrate. The other substance is a C-18 alpha-glucosiduronate. Removal of the acetyl and ester groups from C-18 alpha-glucosiduronate gave the alpha-glucosiduronic acid in 84% yield and the 17-isoaldosterone alpha-glucosiduronic acid in 12% yield. 7. The rate at which several types of beta-glucuronidase hydrolyse the foregoing steroidal alpha- and beta-glucosiduronic acids is given.

Aldosterone↗

Acth-independent Cushing's syndrome: bilateral cortisol-producing adrenal adenomas.

ACTH-independent Cushing's syndrome (CS) usually results from a solitary adrenocortical adenoma. We recently encountered a patient with ACTH-independent CS associated with bilateral adrenal enlargement. The evaluation led us to consider some rare but interesting entities. The patient was a 69 year-old woman who had a 10-15 year history of controlled hypertension, back pain associated with osteoporosis, easy bruising, and truncal obesity. Her medications included conjugated estrogens. Physical examination revealed classical features of CS. She had a raised blue lesion on her buccal mucosa. Plasma cortisol concentrations were elevated at 36 (a.m.) and 38 (p.m.) microg/dL. Urinary free cortisol was normal at baseline (65 microg/24 hours) but failed to suppress adequately in response to the low-dose dexamethasone suppression test (75 microg/24 hours). The plasma ACTH concentration was undetectable. Plasma cortisol concentrations failed to suppress (37 microg/dL) with an 8 mg overnight dexamethasone test. A CT scan of the abdomen revealed bilateral adrenal masses. The possibilities of food-induced CS and primary pigmented nodular adrenal disease were excluded by a lack of marked stimulation in cortisol secretion to a mixed-meal and dermatologic confirmation of the buccal mucosa lesion as an angioma and not a blue nevus. Adrenal venous sampling showed cortisol secretion from both adrenals. The patient underwent bilateral adrenalectomy with pathology confirming bilateral adenomas. This case illustrates an unusual application of selective venous sampling in the CS evaluation and raises questions about the pathogenesis of cortisol-secreting adrenocortical adenomas.

Journal Article↗