Penile scintigraphy for priapism in sickle cell disease.

UNLABELLED: Penile scintigraphy with [99mTc]pertechnetate/99mTc-RBCs was performed in patients with sickle cell disease patients who had priapism to assess the role of this imaging procedure in directing the clinical management of these patients. METHODS: Fifteen studies were performed in 13 patients who were treated according to a protocol not dependent on the imaging results. The scintigraphic findings of penile vascular perfusion (stagnant or nonstagnant patterns) were collated retrospectively with the form of treatment needed for relief of the condition. RESULTS: Four of five patients with the nonstagnant perfusion pattern responded to analgesics and intravenous hydration. Four of eight patients with the stagnant pattern did not require any aggressive interventions such as corporeal aspiration/irrigation, intracorporeal epinephrine or glans-cavernosa shunt. CONCLUSION: Whereas the nonstagnant scintigraphic finding appeared to be a favorable indicator for conservative treatment, the stagnant finding was apparently noncontributory. In addition, no correlation was found between these two types of scintigraphic patterns and the subsequent sexual potency of these patients.

Studies in porphyria. II. Evidence for a deficiency of steroid delta-4-5-alpha-reductase activity in acute intermittent porphyria.

Patients with the genetic liver disease, acute intermittent porphyria (AIP), have a defect in the reductive transformation of steroid hormones that is manifest by the disproportionate generation of 5beta-steroid metabolites from precursor hormones. 5beta-steroid metabolites were earlier shown to be potent inducers experimentally of delta-aminolevulinate synthetase (ALAS), the mitochondrial enzyme that is rate-limiting in porphyrin synthesis, and that is found at high levels of activity in the livers of AIP patients. In this report, the basis for the defective steroid metabolism in AIP has been shown, through studies with the (14)C-labeled adrenal hormone 11beta-hydroxy-Delta(4)-androstenedione, to reside in a substantial deficiency of hepatic steroid Delta(4)-5alpha-reductase activity. This enzymic deficiency was found in all seven AIP patients studied, and ranged from 34% to as much as 70% below the mean enzyme activity characterizing normal subjects. The functional consequence of the low levels of 5alpha-reductase activity in AIP is to divert the reductive transformation of certain natural hormones from the 5alpha- to the 5beta-pathway; the latter is the metabolic route through which endogenous steroids having the potential for inducing hepatic ALAS are generated. It is not presently known whether the 5alpha-reductase deficiency in AIP is acquired in some fashion or whether it has partial genetic determinants. It seems probable, however, that this enzymatic abnormality, coupled with the dramatic increase in hormone synthesis that occurs at puberty, may be of major importance in determining clinical expression of the latent gene defect for AIP in many individuals. The 5alpha-reductases for steroid hormones are known to be localized in the endoplasmic reticulum of hepatic cells and the present findings in AIP thus represent the first demonstration that an enzymic component of these membranous structures is functionally abnormal in this hereditary liver disease.

Studies in porphyria. I. A defect in the reductive transformation of natural steroid hormones in the hereditary liver disease, acute intermittent porphyria.

A variety of 5beta steroid metabolites derived from hormones natural to man are potent inducers experimentally of delta-aminolevulinate synthetase, the rate-limiting enzyme in porphyrin-heme formation. This mitochondrial enzyme is found at high levels of activity in the livers of patients with the genetic disease, acute intermittent porphyria (AIP). In this study the metabolism of (14)C-labeled testosterone was examined in AIP patients to determine whether there was a disproportionate conversion of the hormone to its 5beta, compared to its 5alpha metabolite. The results indicate that AIP subjects do generate a substantially greater than normal fraction of 5beta metabolite from this steroid; the excessive degree of ring A reduction of testosterone taking place via the 5beta pathway in the porphyric patients averages 350% greater than in the nonporphyric subjects. In one asymptomatic AIP patient the disproportionate generation of 5beta metabolite from the hormone reached a level 10 times the normal mean. Studies with a second (14)C-labeled hormone, dehydroisoandrosterone, whose metabolism in man resembles that of testosterone, confirmed the derangement in reductive transformation of steroids found in the individuals carrying the genetic lesion of AIP. These findings define a new endocrine abnormality in AIP patients and raise the possibility that endogenously derived 5beta steroids may contribute by an induction mechanism to the increased levels of hepatic delta-aminolevulinate synthetase activity found in AIP patients.

Increased survival of sickle-cell erythrocytes after treatment in vitro with sodium cyanate.

Cyanate reacts with the amino-terminal valine residues of hemoglobin S and prevents the sickling in vitro of 50-80% of the erythrocytes from patients with sickle-cell disease. The purpose of the studies reported here was to determine whether this anti-sickling effect would increase the survival of cyanate-treated cells that were returned to the patient. In seven subjects with sickle-cell disease, the mean 50% survival of (51)Cr-labeled sickle erythrocytes was increased from 9.9 to 20.7 days (normal 25-35 days) after treatment of the cells in vitro with sodium cyanate. These results provide evidence that the antisickling effect of cyanate observed in vitro is retained in vivo, and strengthen the rationale for further investigation of cyanate as a possible therapeutic agent in sickle-cell disease.