SHORT PAPERS
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Reduction of Serum Testosterone Levels During Chronic Glucocorticoid
`
`Therapy
`
`MICHAEL R. MacADAMS, M.D.; RICHARD H. WHITE, M.D.; and BRADLEY E. CHIPPS, M.D.;
`Sacramento, California
`
`The effect of chronic glucocorticoid therapy on serum
`testosterone levels was studied in men aged 67 i 4 (SD)
`years with chronic pulmonary disease. The serum
`testosterone level was reduced in 14 of 16 patients to a
`mean value of 21 1 j: 93 ng/dL, compared with
`449 i 1 1 1 ng/dL in 1 1 age- and disease-matched
`control patients (p < 0.001). The corticosteroid dosage
`and the serum testosterone level were inversely related
`(r = -0.78). Testosterone binding to serum proteins was
`not significantly affected. Basal gonadotrophin levels were
`not elevated while their secretory responses to exogenous
`gonadotrophin-releasing hormone (GnRH) were intact. We
`conclude that glucocorticoid therapy commonly reduces
`serum testosterone levels in older men due to alteration
`of hypothalamic GnRH secretion.
`
`EXOGENOUS GLUCOCORTICOIDS acutely reduce testoster-
`one levels in men (1, 2) and interfere with ovulation in
`women (3). These effects may, in part, be explained by a
`direct suppression of gonadal steroid secretion (1, 2, 4,
`5). In addition, chronic prednisolone therapy inhibits pi-
`tuitary gonadotrophin secretion in women (6). The effect
`of chronic glucocorticoid administration on the hypo-
`thalamic-pituitary-gonadal axis in men has not been pre-
`viously studied. Our findings suggest that glucocorticoid
`therapy frequently causes a major reduction in serum tes-
`tosterone levels and that this effect appears to be mediat-
`ed by suppression of the secretion of gonadotrophin-re-
`leasing hormone (GnRH) by the hypothalamus.
`
`Methods
`
`We studied 16 men with chronic obstructive pulmonary dis-
`ease (mean age, 67 i 4 [SD] years) who had been taking ei-
`ther prednisone or methylprednisolone for at least 1 month and
`who had been on a stable dosage of glucocorticoid for at least 1
`week. No patient had any physical signs or history of hypo-
`thalamic, pituitary, or gonadal disease preceding the start of
`glucocorticoid therapy. Eight patients were being treated on a
`daily basis, and 8 patients were receiving doses on alternate
`days.
`Eleven age-matched (mean age, 64 i 5 years) and disease-
`matched patients not receiving glucocorticoid therapy were se-
`lected as controls. The forced expiratory volume in 1 second in
`the patients receiving steroids (1.1 :1: 0.4 L) was not signifi-
`cantly different from that in the control group (1.3 i 1.0 L).
`All patients were receiving multiple medications, which in-
`variably included a theophylline preparation and a beta-adre-
`nergic agonist. No patient receiving a gonadal steroid prepara-
`tion was included. The average number of medications taken,
`other than glucocorticoids, was five in both groups. Because
`morbid obesity reduces serum testosterone levels by altering
`protein binding (7), patients whose weight was greater than
`
`>From the Division of General Medicine, Department of Internal Medicine,
`University of California, Davis; Sacramento, California.
`
`648
`
`Annals of Internal Medicine. 1 986; 1 04:648-65 1.
`
`30% above ideal weight were excluded. The mean weight of
`patients receiving glucocorticoids was 81 i 11 kg, which was
`not significantly different from the mean weight of 73 i 13 kg
`in the control group. Patients with biochemical evidence of thy-
`roid or liver disease were also excluded.
`Serum testosterone levels were measured by radioimmunoas-
`say (8). Cross-reactivity with 5-alpha-dihydrotestosteroné (sta-
`nolone) was 3.4%; with androstanediol, 2.2%; and with 1l-ox-
`otestosterone, 2.0%. The normal range for testosterone in adult
`men in this assay is 300 to 1000 ng/dL. The percentage of total
`testosterone not bound to protein was determined by centrifugal
`ultrafiltration using radiolabeled testosterone (9). The normal
`range for adult men in this assay is 1.5% to 3.7%. The coeffi-
`cicnt of variation for both of these assays was 11%.
`Serum samples were taken from six glucocorticoid-treated
`patients and six control patients before and 30 and 60 minutes
`after intravenous administration of 100 pg of GnRH (Factrel;
`Ayerst Laboratories, New York, New York), samples were as-
`sayed for luteinizing and follicle-stimulating hormones by ra-
`dioimmunoassay using Clinetics kits (Tustin, California). The
`higher of the two stimulated values for each gonadotrophin was
`designated the “peak” value. All samples were frozen at -20 °
`C or lower and submitted for assay within 72 hours. Assays
`were done by Roche Biomedical Laboratories (Raritan, New
`Jersey).
`Results between treatment groups were compared with the
`unpaired, two-tailed Student’s t-test. The correlation between
`the average daily dosage of glucocorticoid and the serum testos-
`terone level was analyzed with Pearson’s correlation coefficient.
`For the purpose of this analysis, we assumed that the relative
`potencies of prednisone and methylprednisolone were, on a
`weight basis, equal. The average daily glucocorticoid dosage in
`patients given alternate-day treatment was defined as one half of
`the total glucocorticoid dose taken every 2 days. Data are pre-
`sented as means i SD. The protocol was approved by the Hu-
`man Subjects Review Committee at the University of Califor-
`nia, Davis, School of Medicine.
`
`Results
`TESTOSTERONE LEVELS
`
`As shown in Figure 1A, the mean total level of serum
`testosterone in the control group was 449 i 111 ng/dL.
`Only 1 of these 11 men had a testosterone level below 300
`ng/dL. In contrast, the mean level in the patients taking
`glucocorticoid was significantly lower, 211 i 92 ng/dL
`(p < 0.0001). Of these 16 patients, only 2 had testos-
`terone levels above 300 ng/dL.
`The mean testosterone level in the patients who were
`receiving a fixed dose of glucocorticoid each day (mean,
`24 mg/d) was 195 i 108 ng/dL, which was not signifi-
`cantly different from the level of 226 i 78 ng/dL in the
`patients who were receiving alternate-day treatments
`(mean dose of 23 mg alternating with 3 mg every other
`day). However, as indicated in Figure 1B, the average
`© 1 986 American College of Physicians
`
`WCK1037
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`daily dosage of prednisone or methylprednisolone was in-
`versely related to the testosterone level (r = -0.78).
`The mean serum testosterone level in patients receiving a
`“low” dose of corticosteroid (15 mg/d or less), 270 i 89
`ng/dL, was significantly reduced when compared to that
`of the control patients (p < 0.01) and was significantly
`greater (p < 0.01) than the mean testosterone level of
`137 i 68 ng/dL in patients taking more than 15 mg/d of
`prednisone or methylprednisolone.
`The percentage of total testosterone not bound to pro-
`tein was assayed in 13 glucocorticoid-treated patients and
`in 10 control patients. Our findings showed no significant
`difference between the two groups: 1.8 i 0.6% unbound
`testosterone in the glucocorticoid-treated patients and
`1.5 i 0.5% in the control patients.
`
`LUTEINIZING AND FOLLICLE-STIMULATING HORMONE
`LEVELS
`
`In six patients treated with glucocorticoid and in six
`control patients, basal and GnRH-stimulated luteinizing
`hormone (LH) and follicle-stimulating hormone (FSH)
`levels were measured (Figure 2). Basal LH (14 :l: 2
`mIU/mL) and FSH levels (19 :1: 5 mIU/mL) in the
`control group were not significantly different from the
`basal LH (11 i 4 mIU/mL) and FSH levels (12 :l: 7
`mIU/mL) in the glucocorticoid-treated group, despite
`the low testosterone levels in the latter group. After 100
`pig of GnRH was administered intravenously, peak LH
`and FSH levels in the controls (45 :1: 15 and 31 j: 12
`mIU/mL, respectively) and glucocorticoid-treated pa-
`tients (37 :1: 17 and 21 i 15 mIU/mL,
`respectively)
`were not significantly different.
`
`Discussion
`
`Our results indicate that chronic glucocorticoid thera-
`py commonly lowers the serum testosterone level in men
`who have moderate to severe chronic obstructive pulmo-
`nary disease. This effect can be seen at dosages of predni-
`sone or methylprednisolone as low as 15 mg/d.
`Because most of the testosterone measured in serum is
`
`protein bound, conditions that reduce the concentration
`of testosterone-carrier proteins can reduce the serum tes-
`tosterone level. Glucocorticoid therapy has been reported
`to reduce the level of sex-hormone-binding globulin (10),
`the primary testosterone carrier protein. In our study we
`did not measure levels of sex horrnone-binding globulin
`directly, but we did not find that glucocorticoid therapy
`changed the percentage of total testosterone that was not
`bound to protein. Thus, in our patients, glucocorticoid
`therapy reduced the total as well as the biologically more
`active unbound testosterone.
`
`Several reports have noted that men with Cushing’s
`disease have low serum testosterone levels (11-13). Al-
`though there may be several mechanisms for this elfect,
`our findings indicate that the elevated serum glucocorti-
`coid level in Cushing’s disease is of primary importance
`in the hypogonadism frequently seen in these patients
`(13).
`Although the primary source of testosterone in men is
`the testicles, the small adrenal contribution might be ex-
`
`700
`
`600
`
`500
`
`400
`
`300
`
`200
`
`I00
`
`
`
`
`
`TOTALTESTOSTERONE,ng/dl
`
`A
`
`CONTROL
`
`GLUCOCORTICOID
`TREATED
`
`700
`
`600
`
`500
`
`400
`
`0
`
`y= —9.5x +414
`r=-0.78
`
`300
`
`200
`
`I00
`
`
`
`
`
`TOTALTESTOSTERONE,ng/dl
`
`I0
`20
`30
`40
`50
`AVERAGE GLUCOCORTICOID DOSE, mg/D
`B
`Figure 1. Total testosterone levels in control patients (closed cir-
`cles) and patients receiving glucocorticoid therapy daily (open cir-
`cles) or on alternating days (triangles). In Figure 1A, the horizontal
`lines indicate mean :t SD. Figure 1B shows the correlation between
`the testosterone level and average glucocorticoid dose.
`
`pected to be suppressed during exogenous glucocorticoid
`therapy. However, it is extremely unlikely that this effect
`accounts for the greater than 50% reduction in the serum
`testosterone levels that we observed. Other potentially
`
`MacAdams at al. I Glucocorticoids and Serum Testosterone
`W K1037
`Page 2
`
`649
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`Page 2
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`

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`LHm|U/ml
`
`60
`
`U1 0
`
`m04Aooo
`
`5
`
`FSHm|U/ml
`
`Figure 2. Serum luteinizing hor-
`mone (LH) and follicle-stimulating
`hormone (FSH) concentrations be-
`fore and after administration of
`gonadotrophin-releasing hormone
`(GnRH) in six control patients (sol-
`id circles) and six glucocorticoid-
`treated patients (open circles). The
`arrows represent
`the intravenous
`injection of 100 pg of GnRH. Data
`are means :1: SD.
`
`O
`
`30
`
`60
`
`0
`
`30
`
`so
`
`TIME (min)
`
`TIME (min)
`
`the serum testos-
`significant factors that might affect
`terone level, such as patient age, severity of chronic ob-
`structive pulmonary disease, and use of concomitant
`drugs, were controlled for by selecting an age- and dis-
`ease-matched group of patients for comparison. Only 1 of
`the 11 control patients had a reduced testosterone level,
`in contrast to 14 of the 16 glucocorticoid-treated patients.
`Nevertheless, we cannot exclude the possibility that ad-
`vancing age, chronic illness, or medications may have
`potentiated the effect we observed of chronic glucocorti-
`coid therapy on the serum testosterone level.
`Previous reports have shown that glucocorticoids pro-
`duce a direct suppressive efi'ect on gonadal steroid secre-
`tion (1, 2, 4, 5). If this mechanism were the only one
`responsible for the reduction in the serum testosterone
`levels that we observed, baseline gonadotrophin levels
`should have been elevated. The finding of normal FSH
`and LH levels indicates that glucocorticoid therapy sup-
`presses the secretion of LH and FSH by the pituitary
`gland, although it does not exclude a coexistent suppres-
`sion of testicular function. When synthetic GnRH was
`administered and the LH and FSH secretory responses
`monitored, no significant differences between glucocorti-
`coid-treated patients and eugonadal control patients were
`found, indicating an intact pituitary response. Although
`these data do not exclude a more subtle direct inhibition
`
`of pituitary gonadotrophin secretion in glucocorticoid-
`treated men, as has been reported in glucocorticoid-treat-
`ed women (6), they clearly indicate that glucocorticoid
`therapy exerts a suppressive influence on the secretion of
`GnRH by the hypothalamus.
`Our findings may have some important clinical ramifi-
`cations. For example, in glucocorticoid-treated men with
`chronic lung disease, the frequent occurrence of impo-
`May 1 986 0 Annals of Internal Medicine 0 Volume 104 0 Number 5
`
`650
`
`tence and loss of libido, usually attributed to the effects of
`chronic illness, may actually be due to glucocorticoid-in-
`duced hypogonadism. Similarly, decreased serum testos-
`terone levels may be partly responsible for glucocorti-
`coid-induced osteopenia, since bone mineral content in
`men has been found to be directly related to the circulat-
`ing testosterone level (14). Furthermore, because admin-
`istration of testosterone to hypogonadal men has been
`shown to improve bone mineralization (15), such thera-
`py in glucocorticoid-treated men may be a useful adjunct
`to prevent and treat glucocorticoid-associated osteoporo-
`sis. Regardless of the biologic effects of glucocorticoid-in-
`duced suppression of the serum testosterone level, clini-
`cians should be aware of this phenomenon and recognize
`it as one of the causes of a low serum testosterone level.
`
`>Requests for reprints should be addressed to Michael R. MacAdams,
`M.D.; 2600 Capitol Avenue, Suite 406; Sacramento, CA 95816.
`
`References
`1. DOERR P, Puucr-: KM. Cortisol-induced suppression of plasma testos-
`terone in normal adult males. J Clin Endocrinol Metab. 1976;43:622-9.
`2. SCHAISON G, DURAND F, Mowszowrcz I. Effect of glucocorticoids on
`plasma testosterone in men. Acta Endocrinol (Copenh). 1978;89:126-
`31.
`3. SPRAGUE RG, Powr-:3 MH, MASON HL, et al. Observations on the
`physiologic effects of cortisone and ACTH in man. Arch Intcm Med.
`1950;85:199-258.
`4. EVAIN D, MORERA AM, SAEZ JM. Glucocorticoid receptors in intersti-
`tial cells of the rat testis. J Steroid Biochem. l976;7:l135-9.
`5. HSUEH AJW, ERICKSON GF. Glucocorticoid inhibition of FSH-induced
`estrogen production in
`cultured rate granulosa
`cells. Steroids.
`1978;32:639-423.
`6. SAKAKURA M, TAKEBE K, NAKAGAWA S. Inhibition of luteinizing hor-
`mone secretion induced by synthetic LRH by long-term treatment with
`glucocorticoids
`in human subjects. J Clin Endocrinol Mctab.
`l975;40:774-9.
`7. GLASS AR, SWERDLOFF RS, BRAY GA, DAHMS WT, ATKINSON RL.
`Low serum testosterone and sex-hormone-binding-globulin in massively
`obese men. J Clin Endocrine] Metab. 1977;45:1211-9.
`8. AULETTA FJ, CALDWELL BV, HAMILTON GL. Androgens:
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`testos-
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`terone and dihydrotestosterone. In: JAFFE BM, BEI-IRMAN HR, eds.
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`9. VLAI-Ios I, MACMAHON W, SGOUTAS D, BOWERS W, THOMPSON J,
`TRAWICK W. An improved ultrafiltration method for determining free
`testosterone in semm. Clin Chem. 1982;211:2286-91.
`10. VERMEULEN A, VERDONCK L, VAN DER STRAETEN M, ORIE N. Ca-
`pacity of the testosterone-binding globulin in human plasma and influ-
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`J Clin Endocrinol. 1969;29:l470-80.
`I1. MCKENNA TJ, Loaaea D, LACROIX A, RABIN D. Testicular activity in
`Cushing's disease. Acta Endocrinol (Copenh).
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`I2. Boccuzzx G, ANGEL] A, Bisaocci D, FONZO D, GAIDANO GP, CERE-
`__?_T_
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`SA F. Effect of synthetic luteinizing hormone releasing hormone (LH-
`RH) on the release of gonadotropins in Cushing’s disease. J Clin Endo-
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`l975;40:892-5.
`13. LuToN J-P, THIEBLOT P, VALCKE J-C, MAI-IOUDEAU JA, BRICAIRE H.
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`I5. BARAN DT, BERGFELD MA, TEITELBAUM SL, AVIOLI LV. Effect of
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`l978;26:103-6.
`
`Hepatic Veno-occlusive Disease Associated with Renal Transplantation and
`Azathioprine Therapy
`JAMES G.
`ALEXANDRA E. READ, M.D.; RUSSELL H. WIESNER, M.D.; DOUGLAS R. LaBRECQUE, M.D.;
`TIFFT, M.D.; KEVIN D. MULLEN, M.B., M.R.C.P.I.; ROBERT L. SHEER, M.D.; MARY PETRELLI, M.D.;
`EDMOND S. RICANATI, M.D.; and ARTHUR J. MCCULLOUGH, M.D.; Cleveland, Ohio; Rochester,
`Minnesota;
`Iowa City,
`Iowa; and Syracuse, New York
`
`Four patients with renal transplants developed hepatic
`veno-occlusive disease after immunosuppressive therapy
`with azathioprine. Severe progressive portal hypertension
`developed in all patients, with the clinical presentation
`varying from a mild viral-like syndrome to rapidly
`fulminant liver failure and death. The disease was
`associated with cytomegalovirus infection but not with the
`dose of azathioprine, the type or duration of transplant, or
`the type of underlying kidney disease. In view of the high
`mortality rate associated with veno-occlusive disease (a
`combined 55% in our four patients and in five reported in
`the literature) and wide spectrum of clinical presentation
`in patients with renal transplants, a high index of suspicion
`is required and aggressive intervention indicated.
`
`HEPATIC VENO-OCCLUSIVE DISEASE is a nonthrombotic
`obliterative process of the central or sublobular hepatic
`veins (1) that is characterized by ascites, hepatomegaly,
`and a varied clinical outcome. Worldwide, the hepatotox-
`ic pyrrolizidine alkaloids that occur naturally in plants
`are its most frequent cause (2-7). However, in the United
`States, chemotherapy (8-10) and irradiation (11, 12),
`especially in patients who have had bone marrow trans-
`plants (13-17), appear to be the commonest causes.
`We describe hepatic veno-occlusive disease in four pa-
`tients with renal transplants who were treated with aza-
`thioprine. We also have reviewed the literature and
`emphasize the importance of recognizing this potentially
`fatal disease in a continuously enlarging pool of patients.
`
`Case Histories
`PATIENT 1
`
`After 9 years of being maintained on daily treatments with
`azathioprine (125 mg) and prednisone (10 mg) for her renal
`
`D From the Divisions of Gastroenterology, Nephrology, and Pathology, Cleve-
`land Metropolitan General Hospital, Case Western Reserve University, Cleve-
`land, Ohio; the Division of Gastroenterology, Mayo Clinic and Mayo Foundation,
`Rochester, Minnesota; the Division of Gastroenterology-I-lepatology, University
`of Iowa, Iowa City, Iowa; and St. Joseph’s Health Center, Syracuse, New York.
`
`Annals of Internal Medicine. 1 986:1 04:65 1 -655.
`
`transplant, a 31-year-old woman developed nonspecific pain in
`her right upper abdomen (Table 1). Esophagogastroduodenos-
`copy and upper gastrointestinal barium studies had normal
`findings, but an abdominal ultrasound revealed diffuse hepatic
`parenchymal abnormalities and an enlarged portal vein. A com-
`puted tomographic (CT) scan of the abdomen showed hepato-
`splenomegaly, and a liver-spleen radionuclide scan revealed dif-
`fuse parenchymal disease with increased bone marrow activity.
`The hepatic veins and inferior vena cava were patent on both
`the ultrasound and CT scan. Serum aminotransferase levels
`were elevated twofold, but the serum bilirubin and alkaline
`phosphatase levels were normal. Cytomegalovirus titers were
`positive (12256), but serologic tests for hepatitis A, hepatitis B,
`and Epstein-Barr virus were negative. Autoantibodies (antinu-
`clear, antismooth muscle, and antimitochondrial) were also ab-
`sent. Liver biopsy results were consistent with veno-occlusive
`disease (Table 2).
`Azathioprine therapy was discontinued for 6 months but was
`reinitiated at 25 mg/d because of renal allograft rejection. Fif-
`teen months after an episode of hematemesis, an upper endo-
`scopic examination showed esophageal varices for the first time.
`Repeat liver biopsy studies showed the histologic changes of
`veno-oclusive disease similar to those on the first biopsy but less
`severe. Cyclophosphamide (100 mg/d) was substituted for aza-
`thioprine, and the patient has done well for 30 months.
`PATIENT 2
`
`After renal transplantation, a 53-year-old man received daily
`immunosuppressive treatments with azathioprine (150 mg) and
`prednisone (20 mg) (Table 1). Six months later, fatigue, jaun-
`dice, and ascites developed. Liver function tests revealed total
`and direct bilirubin levels of 11.8 and 9.2 mg/dL, respectively,
`an aspartate aminotransferase level of 116 U/L (laboratory
`normal, 31), and an alkaline phosphatase level of 456 U/L
`(normal, <200). Serologic tests for hepatitis A and B were
`negative, but a test for cytomegalovirus was positive at a titer of
`1:10. Abdominal ultrasound and CT scanning showed hepa-
`tomegaly and ascites. Cyclophosphamide (125 mg/d) was sub-
`stituted for azathioprine. After 4 months without improvement,
`a liver biopsy was done and showed histopathologic findings
`consistent with veno-occlusive disease (Table 2). An endoscop-
`ic retrograde cholangiogram was normal, as was a venogram of
`the large hepatic veins and inferior vena cava. The patient died
`2 months later of progressive hepatic failure.
`©1 986 American College of Physicians
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`”.;‘-:%%5l‘xi'“;“/
`
`.,
`f~r"=r>r.‘3?son, Wis,
` Y 08 'I&:‘o'o
`
`5.'%7”R
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`

`
`Annals of Internal Medicine
`
`Volume 104 c Number 5
`May 1986
`
`CONTENTS
`
`ARTICLES
`
`AIMEAS 104(5)599-738(1986)
`US ISSN 0003-4819
`
`Detection of Aortic Insufficiency by Standard Echocardiography, Pulsed Doppler Echocardiography, and Ausculta-
`tion: A Comparison of Accuracies. P.A. Grayburn, M.D. Smith, R. Handshoe, B.J. Friedman, and AN. DeMaria .
`.
`.
`.
`Acute Febrile Cerebrovasculitis: A Syndrome of Unknown, Perhaps Rickettsial, Cause. R.P. Wenze/, F.G. Hayden,
`D.H.M. Gro'sche/, R.A. Sa/ata, W.5‘. Young, J.E. Greenlee, S. Newman, P.J. Mi//er, K.E. Hechemy, W. Burgdorfer, M.G.
`Peacock, and L.J. Rubinstein .
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`Active Smoking Depresses Prostaglandin Synthesis in Human Gastric Mucosa. G.F. Quimby, C.A. Bonnice, $.i-/.
`Burstein, and G.L. Eastwood .
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`Infectious Complications in Adults with Bone Marrow Transplantation and T-Cell Depletion of Donor Marrow:
`Increased Susceptibility to Fungal Infections. J.D. Pirsch and D.G. Maki .
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`Nosocomial Transmission of Delta Hepatitis. L.A. Lettau, H.J. Alfred, R.H. G/ew, H.A. Fields, M.J. Alter, R. Meyer,
`$.C. Had/er, and J.E. Maynard .
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`Chronic Epstein-Barr Virus Infection Associated with Fever and Interstitial Pneumonitis: Clinical and Serologic
`Features and Response to Antiviral Chemotherapy. R.T. Schoo/ey, R.W. Carey, G. Mi//er, W. Hen/e, R. Eastman,
`E.J. Mark, K. Kenyon, 50. Wheeler, and RH Rubin .
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`Risk of Nosocomial Infection with Human T-Cell Lymphotropic Virus Type IIl/Lymphadenopathy-Associated Virus
`in a Large Cohort of intensively Exposed Health Care Workers. D.K. Henderson, A.J. Saah, B../. Zak, R.A. Kas/ow,
`H. C. Lane, T. Fo/ks, W.C. Blackwe/der, J. Schmitt, D.J. LaCamera, H. Masur, and AS. Fauci .
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`. .599
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`. .606
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`. .61 6
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`. .6 1 9
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`. .63 1 /
`
`. .636
`
`. .644 '
`
`SHORT PAPERS
`Reduction of Serum Testosterone Levels During Chronic Glucocorticoid Therapy. MR. MacAdams, R.H. White, and
`B.E. Chipps .
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`. .648
`Hepatic Veno-occlusive Disease Associated with Renal Transplantation and Azathioprine Therapy. A.E. Read, R.H.
`Wiesner, D.R. LaBrecque, J.G. Tifft, K.D. Mu//en, R.L. Sheer, M. Petre///', E.S. Ricanati, and A.J. McCu//ough .
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`Epidemiology and Treatment of Oropharyngeal Gonorrhea. D.M. Hutt and EN. Judson .
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`. .651
`. .655
`
`BRIEF REPORTS
`
`Successful Warfarin Anticoagulation Despite Protein C Deficiency and a History of Warfarin Necrosis. N.P. Zauber
`and M.W. Stark .
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`. .659
`The Effects of Erythromycin in Patients Treated with Cyclosporine. R. Marte//, D. Heinrichs, C.R. Sti//er, M. Jenner,
`. .660
`P.A. Keown, and./. Dupre .
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`Large lntracranial Arteritis with Giant Cells in Systemic Lupus Erythematosus. D. Scharre, M. Petri, E. Engman, and
`S. DeA rmond .
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`
`DIAGNOSIS AND TREATMENT
`
`Diagnostic Decision: The Utility of Routine Chest Radiographs. T.G. Tape and A./. Mush/in .
`UCLA CONFERENCE
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`Chronic Leukemias: Oncogenes. Chromosomes, and Advances in Therapy. R. Champ/in, R.P. Ga/e, K.A. Foon, and
`D.W._Go/de .
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`REVIEW
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`lntracardiac Thrombi and Systemic Embolization. R.S. Me/tzer, C.A. Visser, and V. Fuster .
`CLINICAL REVIEW
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`The Toxicity of D-Penicillamine in Systemic Sclerosis. V.D. Steen, 5‘. Blair, and 7'.A. Medsger, Jr.
`MEDICINE AND PUBLIC ISSUES
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`The Role of the Primary Physician in Disability Determination for Social Security Insurance and for Workers’
`Compensation. T.S. Carey and N.M. Had/er .
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`New Guidelines on Foregoing Life-Sustaining Treatment in Incompetent Patients: An Anti-Cruelty Policy. S. Braith-
`waite and DC. Thomasma .
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`. .71 1
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`Contents continued on next page
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`WCK1037
`Page 6
`Annals of Internal Medicine 0 May 1 986
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`I-9
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`WCK1037
`Page 6
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`

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`Contents continued from page /-9
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`EDITORIALS
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`Sudden Cardiac Death—1986. A.E. Buxton .
`New Sensitive lmmunoradiometric Assays for
`Thyrotropin. D.5‘. Ross .
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`Geriatric Assessment. M.E. Williams .
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`. .716
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`. .724
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`and the Toxic Oil
`Hypercoagulable States
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`Syndrome .
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`M. Castro Garcia, M. Posada, F. Diaz de Rojas, /.
`Abaitua Borda, and J.M. Tabuenca 0/iver
`Enzyme Immunoassay Screening for Hepatitis B
`Immunization .
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`CA. Benson, H.A. Kess/er, A./I. Harris, K. Kape/l,
`and S. Chakonas
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`Ibuprofen and Aseptic Meningitis .
`D.L. Bouland, N.L. Specht, and DR. Hegstad
`Correction: Outcome from Intensive Care .
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`. .731
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`Correction: Cryptococcal Disease in the Ac-
`quired Immunodeficiency Syndrome .
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`Correction: Blood Product Immunosuppression
`and the Acquired Immunodeficiency Syndrome .731
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`. .731
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`THE LITERATURE OF MEDICINE
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`Book Reviews, Notes, and Listings .
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`. .I-6
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`Information for Authors .
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`. .Begins on I-2
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`. .Begins on I-73
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`. .7 2 7
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`Medical Notices .
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`From Other Pages .
`Morbidity and Mortality Weekly Report: Contents . 1- 1 27
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`Abstracts of Articles .
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`CME Bulletin Board .
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`LETTERS AND CORRECTIONS
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`Vaccination Against Pneumococcal Infection .
`P. Drinka and M. Siewert; H.L. /srae/,' T.C. Eick-
`hoff
`Computer Searching of the Medical Literature .
`P.K. Smith; RB. Haynes and K.A. McKibbon
`Hypocitraturic Calcium-Oxalate Nephrolithiasis .
`G.D. Park and R. Spector; C. Y.C. Pak
`Carcinoembryonic Antigen .
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`Neurosyphilis and Cerebrospinal Fluid Tests .
`S.J. Sperber, C.J. Sch/eupner, and J. Boyd Fran-
`cis; P.E. Dans, L. Cafferty, S.E. Otter, and l?.J.
`Johnson
`Complications of the Acquired Immunodeficien-
`cy Syndrome .
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`B. Clotet, M. Grifol, J. Boix, J. Junca, M. F02, and
`M. Ribas;
`J.K.M. Eeftinck Schattenkerk, C.
`Kléipping, J.D. Spee/man, R../. Van Kete/, and S.A.
`Danner; $.K. Akula, P. W.A. Mansell, and R. Ruiz
`Toxicities of Alkyl Nitrites .
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`Prayer-Meeting Cardioversion .
`RR. Kowey, T.D. Friehling, and RA. Marinchak
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`Calcium and Alcohol-Associated Hypertension .
`S. De Marchi, E. Cecchin, R. Ce//a, and R. Nardini
`Hydrazine Toxicity, Pyridoxine Therapy, and Pe-
`ripheral Neuropathy .,.
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`Hypertension and Cyclosporine .
`J.J. Sennesael, A.G. Dupont, D.L. Verbee/en, L.
`Van Hae/st and L.C. Paul
`Apparent Anaphylaxis from Labetalol
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`. 729
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`Index to Advertisers .
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`. .I-5
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`I-10
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`Annals of Internal Medicine 0 May 1 986
`
`WCK1037
`Page 7
`
`WCK1037
`Page 7