Theoretically, the relationship between plasma aldosterone (PA) and PRA in normal subjects under random conditions should differ from that in patients with primary hyperaldosteronism or primary adrenal failure, but should be similar to that in patients with secondary hyperaldosteronism or hyporeninemic hypoaldosteronism. PA, expressed as a function of PRA, the PA/PRA ratio, provides an index of adrenal sensitivity in normal subjects under routine conditions. The random PA/PRA ratios in patients with primary adrenal disorders did not overlap with those in normal subjects, patients with secondary adrenal disorders, hypertensive subjects, or other patients. A single elevated PA/PRA ratio, i.e. more than 920, associated with elevated PA in 4 patients or normal PA in 6 patients indicated primary hyperaldosteronism in 10 patients. However, 5 of 17 patients with chronic renal failure had elevated PA/PRA ratios, but did not have primary hyperaldosteronism. All 14 patients with secondary hyperaldosteronism had elevated PA associated with normal PA/PRA ratios. A single PA/PRA ratio of less than 28 associated with low PA in 18 patients and a normal PA in 1 patient indicated primary adrenal insufficiency, while a low PA associated with a normal PA/PRA ratio indicated hyporeninemic hypoaldosteronism in 7 patients. Fifty-nine patients with nonadrenal disorders other than renal failure had normal PA and PA/PRA ratios. Therefore, with the exception of patients with advanced renal failure, only a single blood sample is required to establish all diagnoses of disorders of the renin-angiotensin-aldosterone axis under random conditions.
Reports of concurrent thyrotoxicosis and thyroid cancer have appeared in the last three decades. While most of the tumours have been clinically inconsequential, it has been suggested that thyroid carcinomas arising in patients with Graves' disease tend to behave aggressively, while those associated with toxic nodular goitre follow a more benign course. We report a contrary clinical experience with four cases of thyrotoxicosis associated with metastatic thyroid cancer, two of which were fatal. All four patients had toxic nodular goitre. Thyroid eye signs were uniformly absent. Two patients had received 131I therapy; none had other history of irradiation to the head or neck. Antimicrosomal and antithyroglobulin antibodies were absent in all four patients. Thyroid-simulating immunoglobulin, which was measured in one patient, was also absent. Histopathological examination of the resected thyroid glands revealed two papillary cancers. one mixed anaplastic/papillary and one anaplastic cancer. All four patients had cervical node involvement and one had pulmonary metastases. Both patients with anaplastic carcinoma succumbed to their disease within 6 months: neither of the patients with papillary cancer had disease recurrence after 2 and 4 years, respectively. The experience reported here of aggressive thyroid cancer associated with toxic nodular goitre may represent coincidence or, alternatively, it may represent the early recognition of a change in the natural history of toxic nodular goitre.
SUMMARY.A highly specific radioimmunoassay for aldosterone in plasma has been developed utilising extraction from plasma into dichloromethane, an antiserum raised to aldosterone-3-carboxy-methyloxime-BSA and a radio-iodinated derivative of aldosterone. The plasma values obtained after only extraction correlated very well with the results following chromatography over celite. The within-and between-batch variations for plasma pools ranged between 5 and 15%. The range obtained, HXl-1806 pmoVL for 96 random upright subjects, was comparable to others reported. Measurement of plasma aldosterone and plasma renin activity in these subjects showed that both these parameters are higher in subjects under 40 years of age than in those over 40. In addition, plasma aldosterone levels are higher in women than in men even though their plasma renin activity levels are similar. The plasma aldosterone/renin activity ratios which provide an index of adrenal sensitivity to stimulation, are lower in men than in women. The findings in this study suggest that higher aldosterone levels in younger subjects are associated with greater stimulation of the adrenals than in older subjects and that the adrenal is more sensitive in women than in men.The most widely used method for the measurement of aldosterone in plasma is radioimmunoassay. Since the concentration of aldosterone in plasma samples is very low compared to the levels of some potentially cross-reacting steroids, chromatographic purification of samples prior to assay provides the most accurate results especially in samples with abnormal steroid profiles. I, 2 Simpler methods for the purification of samples prior to assay have been reportedr? all of which require extraction into organic solvents. Over the past 10 years direct radioimmunoassays for aldosterone have been promoted. Ogihara et al.6 employed a highly specific antiserum in such an assay. Al Dujaili and Edwards? claimed that a low assay pH and the use of a radio-iodinated derivative greatly enhanced the avidity of the antiserum for aldosterone relative to the other steroids, thus providing a useful direct assay for aldosterone. These direct methods are convenient, cheap and fast, and were reported to give results which were similar to, and correlated with, results obtained following chromatography. However, we were unable to confirm the dramatic pH effect on antibody specificity described by Al Dujaili and Edwards? using the same antiserum and the same assay systemour findings were similar to those of Lun et al. 8 In this study we describe the evaluation of antisera for use in an aldosterone radioimmunoassay using a radio-iodinated aldosterone derivative, and the subsequent development of a highly specific, convenient routine assay for aldosterone following extraction from plasma. This assay was used to examine the reninangiotensin-aldosterone axis in an ambulatory random population. Plasma aldosterone levels are higher in women than in men-this is due to greater adrenal sensitivity to stimulation in women. Plasma al...
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