Pheochromocytoma: diagnosis and management.
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Biomedical subjects
Publications and source records attributed to J H Pratt.
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A prospective study of the incidence of endometriosis encountered in consecutive pelvic explorations was carried out. When study cards were filled out immediately after operation, it was found that one half of the patients had endometriosis. The symptoms, indications for operation, and pelvic findings in patients with endometriosis were compared with those in patients not having endometriosis but with similar operative procedures. The location of the condition and the results of the operation were evaluated. Further comparisons were made as to subsequent symptoms, pregnancy, operations, and hormone requirements, and conclusions were drawn as to risks and benefits referable to the type of operation performed.
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On the basis of the ratios of the estrogen conjugates in their urine (estriol/estrone + estradiol: E3/[E1+E2]), 19 women were divided into two groups: 9 women had ratios less than 0.6 and 10 women had ratios greater than 1.3. All women had measurements made of endogenous estrogens in their plasma by radioimmunoassay. They were then given constant infusions of 3H-estrone, 3H-estradiol and 14C-estriol during days 5-7 and days 20-22 of their cycles, and metabolic clearance rates (MCR) and blood production rates (PB) of estrone, estradiol and estriol were determined. Despite the wide disparity in their ratios of urinary estrogens, no differences could be found between the groups for the MCR's and PB's for all estrogens at either time of the cycle. The mean ratios of PB's (PB3/[PB2+PB1]) of estrone, estradiol and estriol ranged from 0.07 to 0.10 for each group during the cycle. The amounts of estriol entering the blood are small compared to the amounts of estrone and estradiol and do not correlate with the ratios of their urinary conjugates.
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Five hundred and twenty-three patients with endometrial carcinoma treated at the Mayo Clinic from 1952 through 1962 have been followed up for a minimum of 10 years. These patients have been assigned International Federation of Gynecology and Obstetrics classifications retrospectively; 324 were stage IA and 85 were stage IB. Only 24 patients were stage II and 90 were stages III and IV, combined. Most patients were symptomatic, and a significantly greater number of stage IV patients had symptoms for a longer duration. The average age was 59 years; most patients were postmenopausal and there was a high degree of nulliparity. Seventeen and one-half percent of all patients in this series had a second carcinoma at some time, with breast and colon being the most common second primaries. Treatment was basically total hysterectomy and bilateral salpingooophorectomy with postoperative radiation added on an individualized basis. Seventy-four percent of the 523 patients survived 5 years and 64% survived 10 years. This varied from a 90% 5-year survival in 249 patients with stage IA or IB, G1, to a 13% 5-year survival in 46 patients with stage IV lesions.
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In healthy human subjects, the steroidogenic responses to a single injection of alpha 1-18 ACTH by the subcutaneous, intramuscular, and intravenous (IV) routes were assessed by measurement of plasma cortisol levels, 17-hydroxycorticosteroid excretion, and cortisol secretion rates. Results showed that regardless of the parenteral route used, alpha 1-18 ACTH at doses of 1.0 and 0.5 mg was an effective adrenocorticotropic agent; however, with the IV route, the effect was considerably prolonged. The patterns of disappearance within the plasma of alpha 1-18 ACTH and alpha 1-24 ACTH were compared following a single IV injection of these compounds labeled with 125I. ALPHa 1-18 acth produced only a slight initial rise and a slower decline in plasma radioactivity compared to alpha 1-24 ACTH, suggesting slower degradation of alpha 1-18 ACTH. Administered as a single IV injection, alpha 1-18 ACTH has a prolonged effect on steroidogenesis and has potential for being a useful diagnostic and therapeutic ACTH preparation.
Androstenedione and testosterone labeled with 3H and 14C were fused simultaneously at constant rates into the brachial arm vein of 10 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contra-lateral to the infusion. In the 10 men the mean +/- SE value for the fractional metabolism of adrostenedione by muscle is 0.20 +/- 0.30 which is not different from the mean value for the fractional metabolism by androstenedione by adipose tissue, 0.29 +/- 0.04. The mean value for the metabolism of testosterone by muscle, 0.04 +/- *.01, is significantly less than the metabolism by adipose tissue, *.11 +/- 0.01. Interconversion between adrostenedione and testosterone occurs in both tissues. The mean value for pA,T A,M is 0.024 + 0.005 and for pA,T A,AT is 0.024 +/- 0.005. The mean value for pT,A A,M is 0.005 +/- 0.003 and for pT,A A,AT is 0.008 +/- 0.003. The fractional metabolism of these androgens by these tissues is similar to the fractional metabolism of estrone and estradiol by these same tissues. Muscle appears to contribute about 5-12% of the overall metabolism of androstenedione and testosterone and 10-15% to theoverall conversion of androstenedione to testosterone. Adipose tissue contributes about 2-7% of the overall metabolism of these androgens and 5-10% of the overall conversion of androstenedione to testosterone, but less than 2% to the overall conversion of testosterone to androstenedione. In normal men, muscle appears to be more important to the metabolism of androstenedione and testosterone than is adipose tissue.
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The metabolic clearance rate (MCR) and blood production rate (PB) of estriol have been measured in normal, non-pregnant women 21 to 65 years old. 6,7-3H-Estriol was administered as a pulse injection to 4 women between days 5-7 of their menstrual cycle. The disappearance of radioactivity as unconjugated estriol can be described as a function which is the sum of two exponentials. The initial component represents spread into and transfer from a space with a volume of 20.6 +/- 5.4 (SE) l. The mean value for the rate constant of total removal (reversible and irreversible) was 290.2 +/- 78.5 units/day of which 0.34 +/- 0.06 was irreversible. The mean MCRR was 990 +/- 70 l/day/m2. 4-14C-Estriol was infused at a constant rate for 3 1/2 hours to 13 women between days 5-7 of their cycle. The mean MCR was 2,100 +/- 100 l/day or 1,240 +/- 40 l/day/m2. Thirteen women received a constant infusion of 4-14C-estriol between days 20-22 of their cycle. The mean MCR was 2,100 +/- 115 l/day or 1,280 +/- 65 l/day/m2. The mean values for the two phases of the cycle were not significantly different (P greater than 0.1). The mean value for the MCR in 4 post-menopausal women studied in similar fashion was 1,890 +/- 95 l/day or 1,060 +/- 35 l/day/m2. The mean concentrations of estriol were 7.0 +/- 0.7 and 10.9 +/- 0.8 in the follicular and luteal phases of young women, respectively. The mean PB for women in the follicular phase was 14.0 +/- 1.6 mug/day and in the luteal phase was 22.7 +/- 1.9 mug/day. These values were significantly different (P less than 0.01). When the PB's for the 11 women studied in both phases of the cycle were compared the luteal phase values were significantly higher 0.02 greater than P greater than 0.01) using the paired t test. The PB in the 4 post-menopausal women ranged from 5 to 22 mug/day. While there was no difference between the MCR of estriol measured in the two phases of the cycle, the PB of estriol was significantly greater in the luteal phase. Estriol probably contributes little to the overall estrogenic activity in normal, non-pregnant, premenopausal women but could make a more significant contribution in some post-menopausal women.
To determine better the overall regulation of aldosterone by ACTH, the effect of administered ACTH on the aldosterone metabolic clearance rate (MCR), the excretion rates of tetrahydroaldosterone (THAldo), and the acid-labile conjugate (ALC) of aldosterone were studied in healthy male volunteers on a sodium intake in excess of 200 mEq/day. In 7 subjects, the aldosterone MCR increased significantly on the third day of ACTH treatment, as did the excretion of THAldo, but there was a decrease in the excretion of the ALC. One subject receiving ACTH for 6 days showed a steady increase in the aldosterone MCR on days 3 and 6 of treatment. In 2 of 3 subjects receiving ACTH treatment for 3-4 days, plasma aldosterone levels and plasma renin activity showed little change, whereas in 1 subject, both plasma aldosterone and plasma renin activity became suppressed. During ACTH administration there was a sustained increase in the excretion of THAldo, a metabolite formed in the liver, (in contrast to a decreasing excretion of the ALC which is made principally in the kidneys) which suggests that the increased aldosterone metabolism in response to ACTH occurred in the liver. Measurements made of the excretion of THAldo show that the ACTH stimulatory effect on aldosterone secretion may not be as transient as previously reported.
A method is described for the radioimmunoassay of 18-OH-DOC using antibodies generated in rabbits against the carboxymethoxime derivative coupled to bovine serum albumin. The procedure uses 4 ml of plasma with intra and interassay variations of 8 and 9% respectively. Standard 18-OH-DOC added to plasma from an adrenalectomized patient gave a regression equation, Y=0.974X+/-2.210 and a correlation coefficient of 0.999. The only cross reacting steroid, 18-OH-B which may lead to falsely high levels is removed by a single thin layer chromatographic step. Blood levels in normal subjects agree closely with those calculated indirectly by metabolic clearance and secretion rate measurements. ACTH stimulation produced an 18-fold increase in plasma concentration while dexamethasone suppression decreased levels 3-fold. Four hours in the upright position resulted in a decreased plasma concentration while aldosterone increased. No significant response to dietary sodium restriction could be demonstrated.
3H and 14C-Labeled estrone, estradiol, and estrone sulfate were infused at constant rates into brachial arm veins of normal men. In any one experiment, subjects generally received two estrogens, one 3H-labeled and one 14C-labeled. During the infusions, blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In 11 men the mean +/- SE value for the metabolism of estrone by muscle, rho1,0A,M(rho1,0A,M = fraction of estrone in arterial blood which is metabolized by muscle) is 0.17 +/- 0.02 which is not (P greater than 0.1) significantly different from the mean +/- SE value for the metabolism of estrone by adipose tissue, rho1,0A,AT, 0.22 +/- 0.02. Both tissues convert estrone to estradiol, rho1,2A,M(rho1,2A,M = fraction of estrone in arterial blood which is measured as estradiol in venous blood draining muscle) is 0.026 +/- 0.005 and rho1,2A,AT is 0.022 +/- 0.005. Both tissues metabolized estradiol, rho2,0A,M = 0.09 +/- 0.01 and rho2,0A,AT = 0.12 +/- 0.03, and for each tissue the metabolism of estradiol was significantly less than that of estrone (P less than 0.01). Estradiol was converted to estrone by both tissues; rho2,1A,M = 0.007 +/- 0.003 and rho 2,1A,AT = 0.017 +/- 0.003. For estrone sulfate, tissue metabolism could be demonstrated in only 2 of 5 infusions; the values being 0.04 and 0.03, and 0.04 and 0.03 in muscle and adipose tissue, respectively. In only 1 of 3 infusions was evidence obtained for the conversion, by muscle, of estrone sulfate to estrone, rhoS,1A,M = 0.003 and only in one of the 5 subjects was adipose tissue active in this conversion. In no instance were we able to show conversion of estrone sulfate to estradiol by either tissue. In only 1 of 3 infusions could we measure demonstrable conversion of estrone to estrone sulfate by adipose tissue, rho1,SA,AT = 0.02, and we could not demonstrate conversion of estrone to estrone sulfate by muscle or of estradiol to estrone sulfate by either tissue. Both muscle and adipose tissue metabolize and interconvert the free estrogens, estrone and estradiol. The total metabolism by both tissues accounts for 5-10% of the overall metabolic clearance rate of each steroid. The formation of estrone sulfate from estrone and estradiol and the hydrolysis of estrone sulfate occurs to only a minor extent in these tissues.
Two patients with small bowel perforation that occurred during suprapubic catheter insertion are described. Insertion of the catheter with a trocar and with transurethral sound, respectively, was responsible for the perforation. These perforations occurred despite preliminary bladder distention. Small bowel injury was slight in both patients, and neither patient required resection. In 1 patient, the ileocutaneous fistula closed spontaneously, and in the other, oversewing the perforation only was necessary; neither patient has known residual complications.
During a 25-year period on one service at the Mayo Clinic, 262 cervical stumps were removed surgically: 208 vaginally and 54 abdominally. In this series, 46 patients had malignancy of the cervical stump. When a cervical stump is present, it most often can be expeditiously removed during the course of additional vaginal repairs with extremely few risks and complications, and low morbidity.
In a series of 198 exenterative operations performed at the Mayo Clinic for various pelvic malignant lesions, a 5 year survival rate of 33 per cent was obtained. This rate is commendable, since almost 80 per cent of the operations were accomplished for recurrent malignancy. The diminished over-all operative mortality rate of 8.1 per cent, a reduction from 13.5 per cent (1950 through 1962) to 3 per cent (1963 through 1971), is attributed to better methods of urinary diversion and to better management of fluid replacement and of infectious complications. Major complications, excepting bowel fistula and obstruction, now can be controlled reasonably well. When more conservative and equally curative methods of therapy have been exhausted, all patients with pelvic malignancy (whether primary in cervix, vagina, bladder, urethra, rectum, or vulva) should be considered potential candidates for exenteration.
Though endometriosis is a frequent finding in females, it rarely causes obstruction of the small bowel. However, 11 patients with such obstruction were seen at the Mayo Clinic in the years 1950 through 1970. Their ages ranged from 27 years to 51. A portion of involved bowel had to be resected in every case, but most of the lesions were single. Generally the obstructions were subacute and did not produce surgical emergencies. But because the symptoms were neither specific nor acute, the diagnosis seldom was established prior to laparotomy and the majority of the resections were performed without bowel preparation. Nevertheless, morbidity was minor in most cases and there was no mortality. Small-bowel obstruction has not recurred. Endometriosis of the small bowel tends to be limited to the serosa and the muscular coats, not penetrating the mucosa; and obstruction is due to fibrosis and kinking of the bowel. The obstructed segment usually must be resected. If pelvic endometriosis is minimal, no further surgery is necessary. But if the pelvic lesions are extensive, or if multiple sites in the small and large intestines are involved, then more radical resection and bilateral oophorectomy are indicated.