D. L. Hinerman

Spironolactone-Induced Inhibition of Aldosterone Biosynthesis in Primary Aldosteronism : Morphological and Functional Studies

Abstract Twenty-five patients harboring aldosterone-producing adenomas were treated with spironolactone for 2–170 days immediately preoperatively. In the early period of administration of the drug (up to 27 days), plasma and urinary aldosterone decreased sharply while plasma renin activity (PRA) and serum potassium were rising. During this period of time, spironolactone bodies (SB), which form exclusively in cells actively producing aldosterone, were forming rapidly in the tumor cells but not in the inactive glomerulosa cells proper. The SB appear to be a morphological expression of a block in aldosterone biosynthesis. Since SB do not occur in normal fasciculata cells, which, like glomerulosa cells, also synthesize corticosterone, it is concluded that spironolactone inhibition of aldosterone biosynthesis occurs between corticosterone and aldosterone. Recent studies in vitro by others have suggested that the inhibition occurs at the corticosterone-methyl oxidase step, I (Ulicks nomenclature). The great diuresis of sodium and retention of potassium resulting from continued administration of the drug sharply activates aldosterone stimulatory factors. Aldosterone production may return to baseline levels in several weeks but it is inappropriately low in relation to the levels of PRA and serum potassium. With the further passage of time (average 4–6 wk), aldosterone production may increase 50%–100% above baseline levels, suggesting that the block has disappeared or is receding. At this time SB are diminishing in number and by 170 days of the drug they have virtually disappeared. We have hypothesized, among other possibilities, that recovery of the ability to convert corticosterone to aldosterone occurs by virtue of a mechanism activated by sodium deficiency, independent of angiotensin, which stimulates step 1 of the corticosterone-methyl oxidase system. As the block in the final step(s) of the biosynthetic pathway recedes, the existing elevated levels of angiotensin become much more effective in stimulating the production of aldosterone.

Hyperplasia of pancreatic islets associated with extrapancreatic lymphoma and sarcoma

Abstract A preliminary study revealed pancreatic hyperplasia to be present in 29 per cent of 100 consecutive necropsies. Malignant neoplasms coexisted with hyperplasia of islets in 14 (48.3 per cent) of the 29 cases. On the basis of the results of this study, the islets of Langerhans in microscopic sections of pancreas from 20 cases of accidental death (normal controls), 10 cases of extrapancreatic lymphoma, and 12 cases of extrapancreatic sarcoma were quantitatively studied. Significant hyperplasia of the islets was present in both categories of neoplastic disease when compared with the islets in the control group. The assessment of hyperplasia of pancreatic islets was neither difficult nor complex when the observer assigned the proper significance to the presence of an increased percentage of large islets. The method for determining hyperplasia of islets and the significance of its presence are discussed.