Mario Sparagana

Incidental Asymptomatic Adrenal Masses Detected by Computed Tomographic Scanning

Until recently, adrenal masses came to clinical attention either from local symptoms due to massive enlargement or from manifestations of excess hormones production. During the last year, an adrenal mass was identified as an incidental finding in nine patients undergoing abdominal computed tomographic (CT) scanning for unrelated problems. These five men and four women ranged in age from 41 to 73 years. Eight were hypertensive. After the CT scan, each was evaluated for catecholamine or steroid hypersecretion. Only one had clearly elevated urinary vanillylmandelic acid, metanephrine, and catecholamine levels. Equivocal evidence of catecholamine excess was seen in five patients who had slight elevation of one urinary metabolite or of plasma epinephrine or norepinephrine levels. Three patients had no evidence of medullary or cortical hyperfunction on repeated testing. Eight patients were good operative risks and underwent unilateral adrenalectomy without complication. Masses ranging in size from 1 to 4 cm were found in each. These included four cortical adenomas, two adrenal cysts, one adrenal lipoma, and one pheochromocytoma. The pheochromocytoma occurred in the patient with strong biochemical evidence of disease. With wider application of CT imaging, increasing numbers of asymptomatic adrenal masses will be detected. Care in interpreting the clinical significance of these masses and caution in recommending treatment are required.

Primary Hypogonadism Associated with O,P′ DDD (mitotane) Therapy

Mitotane is a drug which is concentrated largely in adipose tissue and the adrenal glands. It has a remarkable specificity for the adrenal cortex and can produce necrosis of that organ; consequently, it has been used as a therapeutic agent for adrenocortical carcinoma. Because of the similarity between adrenocortical and testicular tissue, mitotane could be expected to cause testicular damage; however, there is sparse support for this in the literature. We recently studied a patient who developed impotency due to primary testicular failure at the time that he was treated with mitotane. A testicular biopsy, performed about four months after the drug was discontinued, showed normal appearing Leydig cells and atrophy of the seminiferous tubules with the picture of a maturation arrest. In the four and one half years since he last received mitotane, the patients libido has slowly improved and his plasma testosterone, gonadotropins and LH response to gonadotropin-releasing hormone have become essentially normal. We propose that mitotane can be cytotoxic to the testis as it is to the adrenal cortex.

Hyporeninemic hypoaldosteronism with diabetic glomerulosclerosis

Abstract Several investigations have indicated that lack of renin may be the cause of selective hypoaldosteronism and hyperkalemia in man. We found this syndrome in eight diabetic hyperkalemic subjects by evaluating their renin-angiotensin-aldosterone systems. Their urinary aldosterone, plasma aldosterone, and plasma renin activity showed blunted responses to various provocative stimuli, but their plasma cortisols were normal. Normalization of the serum potassium (cation exchange resin) produced no increase in renin. Infusion of angiotensin II or ACTH raised the aldosterone level, which indicates a responsive adrenal cortex and relatively normal aldosterone biosynthesis. Since the serum potassium level returned to normal with 9 α-fluorohydrocortisone, the distal tubule evidently responds normally to mineralocorticoid. Light and electron microscopy of renal needle biopsies showed, within the juxtoglomerular (JG) areas, nodular sclerosis of the basement membrane of the macula densa, peritubular infiltrates, and a decrease in renin granules. We concluded that the membrane changes and nodular infiltrates present in certain diabetic kidneys produce a barrier which blocks the signals from the macula densa to the JG cells, reduces the amount of renin generated, and thus causes hyporeninemic hypoaldosteronism.

Automated determination of urinary corticosteroids.

A complete automated analysis for urinary corticosteroids was developed using standard Technicon Auto-Analyzer components. Five ml of urine was taken from a 24 hour specimen, and hydrolyzed for 18 hours using beta glucuronidase. Hydrolyzed urine samples were introduced into the system, extracted with methylene chloride, washed with alkali, and reacted at 60°C with the Porter-Silber reagent. All liquid-liquid partitions were carried out automatically using phase separators. Colorimetry was carried out using a 410 mμ interference filter and 50 mm flow cell. Samples were processed at a rate of 10 per hour after an appearance time of 20 minutes. Appropriate blanks were run. Data processing was also automated using an analog to digital convertor and a card punch to print data on cards which were then processed by computer. Mean urinary corticosteroids (mg/24 hrs.) by the Auto-Analyzer method for a series of 52 normal males was 4.8 ± 1.3 (S.D.) and 3.5 ± 1.1 for a series of 48 normal females. A conventional manual method for urinary steroids gave values of 5.0 ± 1.4 and 3.7 ± 1.1 for the males and females respectively. Agreement between the two methods was quite good. Correlation coefficient was 0.76. Standard deviations for replicate samples were ± 0.03 for the automated method and ± 0.06 for the manual method. Analytical recovery of cortisone *added to Addisonian and normal urines was quantitative. The Beer-Lambert relationship was obeyed over the full range of measurement and the curve passed through zero. Specificity for the method was established by comparing the spectra (400–700 mμ) obtained with effluents collected beyond the colorimeter for standard cortisone and urine samples. Applications for the method are presented.

Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one) metabolism in gout

Abstract Excretion of urinary dehydroepiandrosterone (DHA) (1) has been reported as low or absent in subjects with gout. Our own study of 17 control and 17 gouty subjects revealed excretion not only of DHA but also androsterone (A) and etiocholanolone (E) significantly below normal. Plasma DHA SO 4 in three gouty subjects was in the low normal range. Five gout patients and three control subjects were given 14 C DHA intravenously. No urinary 14 C DHA was detected in the former, a mean of 10.5% in that of the latter. Oral administration of 50mg of DHA increased its mean excretion by 19.8% (of C 19 O 2 steroids) in 4 controls, but only 3.0% in three gouty subjects. No correlation could be established between plasma or urinary uric acid and the levels of urinary DHA. It has been demonstrated that the degree of DHA conversion depends on the load presented to the liver. Lower urinary DHA excretion in gouty subjects appears to be due in part to decreased production rate. In addition, the conversion of DHA to A & E was higher in DHA loaded gout patients indicating greater 5 alpha and 5 beta reductase activity. The change of DHA metabolism in gout may be merely coincidental. On the other hand, DHA serves as a precursor for testosterone and the latter is known to facilitate rupture of lysosomes by urate crystals. Lysosomal rupture appears to play a role in breakdown of leukocytes which precedes the inflammation of acute gout.

Modification of the competitive protein-binding assay for corticosterone: Serial measurements in the rat

Abstract An ultramicro method for plasma corticosterone based on a competitive protein-binding technique is described and evaluated. The method proved highly satisfactory for the serial assay of plasma corticosterone in 20 μl of rat plasma. A chronic indwelling catheter placed in the jugular vein was used for continuous infusion of heparinized saline and withdrawal of blood samples for corticosterone measurement at appropriate intervals in undisturbed rats.

Industrial Lung Disease: Report From Veterans Administration Hospital Hines, Illinois

Silicosis associated with asbestosis has been found in several investigations, and the association of asbestosis and mesothelioma is well known. A foundry worker was treated intermittently for chronic obstructive pulmonary disease with superimposed infections. Six years later, a rapidly growing, friable mass appeared in the left lung. Such rapid growth suggested a mesothelioma; however, asbestos bodies were not found in the biopsy specimen.

Case report 94.

This 76-year-old man was admitted initially to the Hines VA Hospital in July 1971 with a pruritic rash, constipation, nocturia and pain in the area of the left hip. The relevant biochemical studies included a serum calcium level of 12.5 mg per ml, a serum phosphorus of 5 mg per 100 ml, an alkaline phosphatase of 350 and on one occasion 1,240 International Units per 100 ml. The parathormone level was 12.4 microliter equivalents per ml, (normal 2.5 to 7.2 for normal calcium). The gastrointestinal tract absorption of labelled calcium was 77% to 85% (normal less than 74%). Because of the patients age and his reluctance to submit to surgery he was treated with oral phosphate. In the following two years the pain in the left hip increased in intensity. Roentgenograms of the left hip obtained in 1973 showed the characteristic changes of Paget disease, with a lyric lesion involving the lateral aspect of the left ilium (Fig. 1).

Chronic Arthritis, Vasculitis and Cutaneous Histoplasmosis

This is an unusual case of histoplasmosis apparently confined to skin and subcutaneous tissue. The pathologist calls it an example of the adage, “You find what you look for.” The patient was given steroids, first for skin rash and later for rheumatoid arthritis. Leg ulcers were diagnosed as thromboangiitis obliterans and the limb was amputated.

Lymphoma and Macroglobulinemia: Report From Veterans Administration Hospital Hines, Illinois

On the basis of clinical and laboratory studies alone, malignant lymphocytic lymphoma may be indistinguishable from Waldenstroms macroglobulinemia. In the case reported here, immunologic data and the presence of multiple infections related to immunoglobulin deficiency suggested macroglobulinemia, but pathologic material and extensive lymphocytic infiltrations were compatible with lymphoma.