The adrenal cortex in internal medicine. II.

Abstract

_., 1966, 2, 914-921 Aldosterone The same interval elapsed between discovery of aldosterone In 1952 by Tait et al. and recognition of the first aldosteroneproducing tumour by Conn in 1954, as between recognition of adrenaline and the first adrenaline-producing tumour. If the rate of clinical progress has not changed in 45 years, that of technical progress has been immensely greater, making possible the isolation of aldosterone from human urine, its crystallization, and the determination and proof by synthesis of its chemical structure, all within two to three years. Shortly afterwards isotope-labelled samples of the hormone were prepared, and with this the daily secretion rate was first estimated. This rapid progress was all the more remarkable because the daily production is only about one-hundredth of that of cortisol.More recently plasma-aldosterone levels have been estimated, though the technique is exacting and the use of isotopes is essential: they average only about a thousandth of the normal plasma cortisol, or about a five-millionth of the normal plasmaglucose content. The now familiar estimations of similar low concentrations of vitamin B1 are made possible by the peculiar sensitivity of a living organism, but there is no equivalent specific organism or chemical reaction for aldosterone. Analysis still involves laborious separation by orthodox chromatographic methods, with assay by modern double isotope-derivative techniques, because the quantities are much too small even for classical microchemical methods. But in spite of the difficulties the general dynamics of aldosterone within the body have now been fairly completely worked out.Aldosterone is secreted into the systemic blood by the zona glomerulosa of the adrenal cortex at a rate which averages 130 ,ug. a day, but varies from 50 to 200 FLg. in normal circumstances. Circulating aldosterone, unlike cortisol, is only mildly bound to plasma protein, the mean being 65 % compared with 95% for cortisol (Daughaday et al., 1961). When blood passes through the liver its aldosterone is almost completely removed. The liver is probably the only major site of aldosterone destruction, for indirect isotopic estimates of the amount of blood cleared of aldosterone per minute coincide very closely with the estimated total liver blood-flow (Bougas et al., 1964). This volume of blood has been called the metabolic clearance rate for aldosterone. The rate of removal from the circulation is such that half the blood content is destroyed in about 30 minutes, and under normal circumstances this will be replaced by freshly secreted aldosterone. The plasma concentration at any time reflects the balance between secretion and destruction, the two being in approximate equilibrium. If any two of these three variables can be measured the third can be calculated.Estimates of total plasma aldosterone obtained either indirectly or directly, by the double isotope-derivative method,give a mean of 0.007 jug./100 ml. . Some of this minute amount leaks into the urine ; the renal clea...

Criteria for distinguishing normal and subnormal adrenocortical function using the Synacthen test

“…Fluorimetric methods ofmeasuring plasma corticosteroids (Braunsberg & James, 1962;Mattingly, 1962Mattingly, , 1963Spencer-Peet, Daly & Smith, 1965;James, Townsend & Fraser, 1967) have renewed interest in the value of acute adrenal stimulation with corticotrophin as a screening test for adrenocortical hypofunction (Landon et al, 1964;Wood et al, 1965;Cope, 1966;Greig et al, 1966;Jasani et al, 1967;Greig et al, 1968). The N-terminal amino acid sequence 1 to 24 of the 1 to 39 chain of natural corticotrophin has been synthesized (Kappeler & Schwyzer, 1961) and is available under the approved name of tetracosactrin.…”

Diagnostische Bedeutung der Proteinbindung von Plasmacortisol, bestimmt durch Dextrangelfiltration

“…Diese Umrechnung diente hauptsächlich dazu, einen Vergleich zu der in der Literatur angegebenen Bindungskapazität [19,36,49] zu ermöglichen. Immerhin soll die fluorimetrische Methode (ll-OHOS im 24 Std-Urin) mit der Sekretionsrate von Oortisol besser korreliert sein, als die Bestimmung der 17-0HOS [9,41].…”

Some recent advances in adrenal diagnosis

“…There is a widespread apprehension that, if steroids are stopped after a long period of therapy, a period of hypoadrenalism may develop of uncertain length. Modern plasma 11-OHCS estimations enable one to observe as closely as may be considered necessary, precisely what is happening in the individual patient (Cope, 1966). If steroid therapy is abruptly stopped in one whose adrenal cortex has been inhibited by prolonged steroid therapy, there will certainly result a temporary period of severe hypoadrenalism, for even the most robust of adrenal cortices will inevitably require time to change from a state of disuse atrophy to one of full normal activity.…”