Testosterone secreting adrenal cortical adenomas

Int. J. Gynaecol. Obsret., 1981,19: 421-428 0 International Federation of Gynaecology & Obstetrics

TESTOSTERONE SECRETING ADRENAL CORTICAL ADENOMAS”

JULIANNE IMPERATO-MCGINLEY,

IVEN S. YOUNG, THERESA HUANG, JOSEPH C. DREYFUS,

III, JON M. RECKLER

and RALPH E. PETERSON Division of Endocrinology, Departments of Medicine and Urology, Cornell University Medical Center, New York, NY, and Department of Medicine, St. Vincent’s Hospital, New York, NY, U.S.A. (Received February 2nd, 1981) (Accepted May 13th, 1981)

Abstract

Introduction

Imperato-McGinley J, Young IS, Huang T, Dreyfus, JC, III, Reckler JM, Peterson RE (Division of Endocrinology, Departments of Medicine and Urology, Cornell University Medical Center, New York, NY and Dept of Medicine, St, Vincent’s Hospital, New York, NY, USA). Testosterone secreting adrenal cortical adenomas. Int J Gynaecol Obstet 19: 421-428, 1981 We report the hormonal and radiological evaluation of two cases of adrenal cortical testosterone that secreted adenomas exclusively. We discuss some of the pitfalls in the diagnosis of this lesion, and summarize the current knowledge of the characteristic hormonal features in the two cases and the 12 cases previously reported.

Adrenal cortical tumors that secrete testosterone as the sole or major steroid with a normal rate of excretion of urinary 17-ketosteroids are unusual. The literature records only 12 cases [ l- 121. With one exception [l] the patients were adult females, and in all cases the plasma levels of testosterone were in the adult male range. Since ovarian tumors [ 131 or ovarian stromal hyperthecosis [ 141 are more frequently the cause of excess androgen production, the virilized female with high plasma testosterone levels and urinary 17-ketosteroid levels is normal usually suspected of harboring an ovarian lesion. Thus, four of the reported subjects with testosterone secreting adrenal adenomas [2,3,6,11] and one subject of this report were initially subjected to bilateral oophorectomy, before the correct diagnosis was made. We report hormonal data on two additional cases of adrenal testosterone secreting tumors, and summarize the current knowledge of both the clinical and hormonal features of this syndrome.

Kew words: Adrenal cortical tumors; TestoHormonal evaluation; sterone secretion; Radiological evaluation; Plasma steroid levels; Urinary steroid excretion.

Case Reports *This work was supported by Research Career Award (REP) K6 AM14241-I 6; Cl&deal Investigator Award $om the National Institute of Arthritis, Metabolism and Digestive Disecrses (JIMcG) K08 AM-0061 S-02; Clinical Research Grant RR-47, Researd Grant m-09421 from the National Institutes of Health.

Case 1

A 49-year-old post-menopausal female was admitted to the hospital with history of hirsutism and increased lethargy for 6 months. Prior to menopause at age 47 years her Int J

Gynaecol Obstet 19

422

Imperato-McGinley et al.

menstrual cycles were regular and occurred every 28 days. She had two pregnancies, both culminating in delivery by Cesarean section. She gave a lo-year history of hypertension, treated with diuretics. Physical examination revealed an obese female weighing 90 kg with a BP 130/96. There was moderate facial acne, a small Buffalo hump, but no striae. There was bilateral temporal hair-line recession with Table I.

an increase in hair on face, trunk, abdomen, and lower back. The clitoris was slightly enlarged. Laboratory tests revealed a diabetic glucose tolerance curve and mild hypokalemic alkalosis. Plasma cortisol at 8 a.m. was 11 ccg/ dl, and 14 pg/dl at 8 p.m. (Table I). Plasma testosterone was 2 15 ng/dl. Urinary 17-ketosteroids and 17-hydroxysteroids were both 12 mg/day (Table II). Plasma cortisol levels

Plasma steroid levels, ng/dl (F = crg/dl). F

Case I 12/M/75 12/22/7Sa 12/24/7Sb l/12/76 l/20/76 6114176 g/2/76

9/S/7Sc g/7/76 9/7/76d 9/11/76e 9/13/76f g/14/76 g/16/76 1 l/22/76 Chse 2 2/l/79 2/s/79

21121798 2/15/79h 414179 4110179

T

DHT

1 l(14) 215 8.5 13 330 Bilateral salpingo-oophorectomy 185 670 IVC 8 525 RAV 27 400 LAV 11 3500 900 15 746 29 824 890 11 934 Left adrenalectomy 11 13 18

15(4) 10 1400 300 1.2 1.1 Right adrenalectomy 14

IVC RAV LAV

A

DEA

25 46 4s 71 37 3s 44 47 35

370 310 2680 3900 305 325 517 274 350

225 700 4290 377 128 122 325 164 122

2 8

75 62

53 180

420 31s 13,000 350 483 510

18 90 15 15 20

40 13,000 5000 30 48

43 23,000 3000 55 63

2

2

12

15

17P

100 290 635 700

46 18,000 1500 110 52

E,

8.7 6.0 9.7

Obstet 19

21 13 17

2.5

1.7

8.6 62 8.9

5.1 23 5.7

0.7

3.1

X 2 days. a After 2 mg dexamethasonejdays b After 8 mg dexamethasonejdays X 2 days. c After 5000 U hCG i.m./days X 3 days. d After infusion 5 U ACTH/h X 8 h. e After 4 mg dexamethasoneldays X 2 days. f After 4 mg dexamethasonejdays X 5 days. 8 After 8 mg dexamethasonejdays X 3 days. hAfter 8 mg dexamethasonejdays X 6 days, and 5000 U hCG i.m. X 3 days. ICV = inferior vena cava, RAV = right adrenal vein, LAV = left adrenal vein. <3 S-15 40-150 SO-300 40-80 S-20 10-30 Normal castrate values F, cortisol, (p.m.); T, testosterone; DHT, Sudihydrotestosterone; A, androstenedione; DEA, dehydroepiandrosterone; 17ctbydroxyprogesterone; E,, estradiol; E, , estrone.

Int J Gynaed

E,


Testosterone secreting adrenal cortical adenomas Table IL

Urinary Steroid Excretion.

Gasel 12115175 12/23/75a 6114176 813 l/76 9/2/76 915J76b 9/7/80c 9/13/76d 9127176 CIzse2 215179 2/12/79e 2/15/79f

F (&day)

17-OH (mglday)

17-KS (mgkday)

31 58 55 30 248

12 12 17 17 13 10 19 15 9.1

12 10 13 13 13 13 15

42 4.5 4.3

5.0 3.3 2.8

3.7

8.4 3.1 2.3

a After 2 mg dexamethasonelday X 2 days and 8 mg of dexamethasonelday X 2 days. b After 5000 U hCG i.m./day X 3 days. c After infuaon 5 U ACTH/h X 8 h. d After 4 mg dexamethasonelday X 5 days. e After 8 mg dexamethasonelday X 3 days. f After 8 mg dexamethasonelday X 6 days, and 5000 U hCG i.m. X 3 days. Normal values 10-80 4-10 4-12 F, cortisol; 17-OH, 17hydroxycorticosteroids; 17-KS, 17ketosteroids.

and urine 17-ketosteroids and 17hydroxysteroids were not suppressed after the administration of low (2 mg/day) or high (8 mg/day) doses of dexamethasone (Tables I and II). X-rays of the chest, lumbosacral spine and skull were normal, as were pelvic and abdominal sonograms. IVP showed lateral displacement of the axis of the left kidney. Total hysterectomy and bilateral salpingooophorectomy were performed. Both ovaries were normal in size, and showed stromal hyperplasia on microscopic examination. There were no palpable suprarenal masses. One week postoperatively the plasma testosterone level was 185 ng/dl. Eight months later the plasma testosterone was 670 ng/dl, and the patient was readmitted for further evaluation. Urinary 17-hydroxycorticosteroids were slightly elevated, but the

423

plasma cortisol levels and urinary excretion of cortisol were normal (Tables I and II). Androstenedione was the only other measured plasma androgen that was elevated (Table I). Plasma estradiol was 8.7 ng/dl (normal <2 ng/ dl in ovariectomized women). Plasma gonadotrophin levels were slightly increased; FSH, 9 ng/ml and LH, 4.5 ng/ml (normal 2-4 ng/ ml), but below the castrate range. Adrenal venous catheterization data revealed a sevenfold step-up in testosterone between the left adrenal venous plasma and the peripheral plasma, with a smaller gradient for Sa-dihydrotestosterone, androstenedione and 17a-hydroxyprogesterone (Table I). hCG, but not ACTH stimulation produced a minimal increase in plasma testosterone. Dexamethasone (4 mg/ day X 4 days) did not decrease the secretion of any adrenal steroid measured, including cortisol. Nephrotomograms showed a 6cm left suprarenal mass. Bilateral adrenal venograms demonstrated a large mass in the left adrenal gland. Following surgical removal of a 100 g, 7.5cm well-encapsulated adrenal adenoma the plasma and urinary steroid levels returned to normal. Case 2 A 5 5-year-old post-menopausal female was admitted to the hospital with a 3-year history of hirsutism, progressive loss of scalp hair, and increased libido. At 40 years of age she underwent a bilateral oophorectomy and hysterectomy for excessive uterine bleeding. Pathological diagnosis was fibromyomata of the uterus. Prior to oophorectomy her menstrual cycles were regular and occurred every 28 days. Diabetes mellitus was diagnosed 1 year prior to admission and she was treated with diet and tolbutamide. Over the past year she had lost 18 kg. One year prior to admission the plasma testosterone was elevated, and abdominal CAT scan was reported as normal. One month prior to admission ultrasonography and a repeat CAT scan of abdomen were reported as normal. Selective venous catheterization was performed and the right adrenal venous effluent Int J Gynaecol Obstet I9

424

Imperato-McGinky et al.

showed a 37-fold step-up in the plasma level of testosterone between the right adrenal and peripheral or left adrenal vein. There was a three- to eight-fold step-up in the plasma levels of all other measured steroids between the right and left adrenal veins (Table I). The much higher plasma level of all steroids in the right adrenal venous effluent is probably due to decreased rate of blood flow from the right adrenal and/or large pulsatile release of ACTH at time of blood collection from the right adrenal. Bilateral adrenal venograms were normal. Physical examination revealed an obese female of 87 kg with BP of 180/80. There was a moderate increase in hair on the face and body, and bilateral temporal hairline recession. The clitoris was slightly enlarged at 1.5 cm. A third abdominal CAT scan showed the right adrenal to be 4 X 1.5 cm and the left adrenal 3 X 2.5 cm with a focal nodule 0.5 X 1.0 cm within the right adrenal. ‘3110docholesterol scan showed a bilateral uptake equally. The plasma FSH was slightly elevated at 6.0 ng/ml and LH 7.0 ng/ml, but below the range expected for an oophorectomized subject. Blood glucose fasting was 150 mg/dl and TSH 6.5 pU/ml (normal <7.0 pU/ml). Testosterone was the only measured peripheral plasma steroid found to be elevated, although plasma estradiol was slightly increased for an ovariectomized woman (4.5 ng/dl). Plasma cortisol was normal and showed a normal diurnal variation (Table I). The urinary excretions of cortisol, 17-hydroxycorticosteroids and 17-ketosteroids were normal, and decreased to below the lower limits of normal following dexamethasone suppression (Table II). After treatment with high doses of dexamethasone, and dexamethasone plus hCG there was no change in the plasma testosterone level. A right adrenalectomy was and a 2.2 cm reddish-brown performed, adenoma was found within the gland. There was no atrophy of the surrounding adrenocortical tissue. The post-operative plasma testosterone was 2 ng/dl.

Int J Gynaecol Obstet 19

Methods

Plasma testosterone, Scrdihydrotestosterone, androstenedione, dehydroepiandrosterone, 17a-hydroxyprogesterone, and cortisol, were measured by RIA by previously described methods [ 15,161. Plasma estradiol, estrone [171, FSH and LH [ 181 were measured by RIA by previously described methods. Urinary 17-hydroxycorticosteroids were measured by the modified Porter-Silber reaction [ 191, urinary 17-ketosteroids by the modified Zimmerman reaction [20], and urinary cortisol by RIA [ 2 11. Discussion

With the exception of adrenal cortical carcinomas [22] most adrenal cortical neoplasms secrete an excess of either cortisol (Cushing’s syndrome) or aldosterone (Conn’s syndrome). Rarely tumors of the adrenal cortex may secrete an excess of the weak androgen dehydroepiandrosterone and are associated with a marked increase in the urinary excretion of 17-ketosteroids [ 23251. In the adult, these tumors account for a small fraction of all adrenal cortical they neoplasms, although in children represent the most common type of adrenal cortical tumor [26], and may present with hirsutism, virilization [ 271, sexual precocity [28,29] or hypertension [29,301. These tumors are frequently malignant [ 26,271. The two subjects of this report and the 12 cases previously reported are unique in that the adrenal adenomas secreted excessive amounts of testosterone, almost exclusively. In all reported cases, and in our two cases the urinary 17-ketosteroid excretion was either normal or minimally elevated. Pathologically these tumors are small (2-8 cm) with the histological appearance of benign adrenal cortical adenomas. In two patients the tumors were identified as ganglioneuromas containing numerous islands of adrenocortical cells [ 7,8].

Testosterone secreting adrenal cortical adenomas

There is only one report of a testosterone secreting adrenal adenoma in a child [ 1 I. All other reported cases were women presenting with hirsutism and virilism, i.e. balding, clitoromegaly and deepening of the cases were voice. Five of the reported diagnosed before the natural menopause [ 1,8- 1 I] and all were amenorrheic. A mild elevation in blood pressure was recorded in six cases [2-S, cases 1 and 23, and in three cases the blood pressure was recorded after surgery and was reported as normal [.5, cases 1 and 21. In other androgen (dehydroepiandrosterone) secreting adrenal neoplasms it is not unusual to find an increased blood pressure with a return of the blood pressure to normal after removal of the adrenal adenoma [24,29,30]. In eight of 14 subjects [2,3,6,8,9,11, cases 1 and 21, following i.m. administration of hCG the plasma testosterone level was increased in all but one subject (case 2). Estrogen administration decreased the plasma testosterone level in two of five subjects studied [ 2,4], whereas in three subjects there was no change in the plasma testosterone levels [3,6,11]. In nine of the 14 cases a laparotomy was initially performed for a suspected ovarian tumor [l-3,6-8,10,11, case 11, and in five subjects a bilateral oophorectomy was carried out prior to adrenal exploration [2,3,6,11, case 11. Two subjects had a bilateral oophorectomy for other indications prior to onset of the hypertestosteronemia [4, case 21. In one subject a laparoscopy was performed prior to exploration of the adrenals [ 121. Thus, in only two patients with intact ovaries were the adrenals presumed to be the initial site of the testosterone excess [5,9]. Attention was initially drawn to the ovaries because either 17-ketosteroid excretion was normal, and/or the plasma level of testosterone rose in response to hCG stimulation. Androgen secreting ovarian tumors are rarely accompanied by increased excretion of urinary 17-ketosteroids [ 131.

425

None of the 14 subjects presented with the clinical manifestations of Cushing’s syndrome. In all subjects, cortisol production was estimated by measurements of the urinary 17-hydroxycorticosteroids before and after administration of dexamethasone. One of the subjects (case 1) was obese and mildly plethoric with a small cervical fat pad and fullness of the supraclavicular spaces. Except for this case none of the subjects had increased urinary 17-hydroxycorticosteroids. It is of interest that the tetrahydro metabolite of 1 ldesoxycortisol accounted for one-third of the total urinary 17-hydroxycorticosteroids in this patient’s urine. This may explain the increased urinary excretion of the 17-hydroxycorticosteroids in the presence of the normal plasma and urine levels of cortisol. The failure of dexamethasone to suppress the plasma level of cortisol, and urinary cortisol and 17-hydroxycorticosteroids in this subject suggest that much of the cortisol and 1 1-desoxycortisol were secreted by the tumor. In this subject and two others [ 5,9] high doses of dexamethasone (8 mg/days X 3 days) failed to suppress the urinary excretion of 17-hydroxycorticosteroids or 17-ketosteroids, whereas in the other subjects dexamethasone decreased the urinary 17-hydroxycorticosteroid excretion [ 2,3,68,10,1 1, case 21. In two of these subjects [2,3], however, the urinary 17-ketosteroid excretion was not suppressed. Eight subjects were given i.v. ACTH [2-4,6,8,9,11, case 11, and the plasma testosterone levels either did not change [6,8,11, case 11, or were decreased. The plasma level of cortisol was measured in 12 subjects and it was normal [1,3-6,812, cases 1 and 21. In six patients the circadian rhythm of plasma cortisol was examined [ 1,4,9,10, cases 1 and 21, and there was an absence of the normal rhythm in two subjects [9, case 11. Testosterone was the only steroid produced in marked excess by the tumors, however in nine subjects [2-4,8,9,11, cases 1 and 21 Inr J Gynaecol Obstet 19

426

Imperato-McGinky et al

plasma androstenedione was assayed and it was slightly elevated in two subjects [8, case 11. Plasma estradiol was measured in only five cases [6,9,11, cases 1 and 21 and it was mildly elevated in all but one case [ 11 I. The mild elevations in plasma androstenedione and estradiol may reflect increased peripheral conversion of plasma testosterone to androstenedione and estradiol, rather than increased secretion of these steroids by the tumor [3 11. Plasma levels of dehydroepiandrosterone were measured in six subjects [ 2,6,8,9, cases 1 and 21 and plasma levels of 17ahydroxyprogesterone were measured in four subjects [6,9, cases I and 2 1. In all subjects the plasma levels of these two steroids were normal [6,91. Plasma levels of Sadihydrotestosterone were measured in three subjects [2, cases 1 and 2 I, and were appropriate for the high testosterone level in two [2, case I] subjects, and was low in one subject (case 2). The plasma levels of FSH and LH were normal in only two [9,11] of the nine patients in whom these hormones were assayed [3,4,6,8,9,11, cases 1 and 21. In six subjects the levels were inappropriately low [3,4,6,8, cases 1 and 21. The adrenal tumor was correctly localized by adrenal venography in four of the five patients subjected to this procedure [4,7-9, case 1 and 21. In one subject arteriography was used to demonstrate the adrenal tumor that had been suspected on basis of an IVP [S]. Also, in our first case the IVP suggested a left suprarenal mass. In three subjects the tumor was correctly localized by CAT scan and ultrasound [8, cases 1 and 21. In our second case two abdominal CAT scans were reported as negative, however on a third attempt the scan correctly localized the tumor. In two subjects 13110docholesterol scanning was used to attempt localization of the tumor [9, case 21, however the uptake of 13110docholesterol was bilateral and equal. In the latter instance the 13110docholesterol scan might have localized the tumor if the patient had first been treated with dexamethasone. There were six attempts to catheterize the Int J Gynaecol Obstet I9

adrenal veins [4,7,8,10, cases 1 and 21. In three patients [4,7,8] it was not possible to catheterize both adrenal veins, although in two of the cases [4,7] the adrenal venous effluent from the side of the tumor only was assayed and the plasma testosterone level was very high. In three cases bilateral adrenal vein catheterization was successful [ 10, cases 1 and 21 and on the basis of assays of plasma adrenal venous testosterone a correct localization of the site of the tumor was made. Thus, the use of the non-invasive sonogram, CAT scan or ‘3110docholesterol scan will probably accurately locate the site of most of these tumors. Although bilateral adrenal vein catheterization can accurately localize the tumor, it will probably not be required in most cases. The use of stimulation tests with hCG or ACTH, and suppression tests with estrogen or dexamethasone to localize an adrenal or ovarian source of excess androgen are of limited value and often misleading [32-341. Adrenal tumors that produce testosterone almost exclusively have all been reported to be benign. Other masculinizing adrenal tumors whose major androgenic steroid secretory product is dehydroepiandrosterone are frequently malignant. Masculinizing tumors of the ovary (hilus cell, arrhenoblastoma, lipoid-cell) in addition to testosterone secrete increased quantities of the precursors 17ar-hydroxyprogesterone of testosterone, and androstenedione [ 32-341. Whereas most of the ovarian tumors are associated with increased estrogen synthesis, testosterone adrenal tumors rarely secrete secreting increased amounts of estrogen. Most adrenal testosterone secreting tumors increased characteristically demonstrate secretion of testosterone in response to hCG. Also, administration of estrogen decreases testosterone secretion, probably by inhibition Since ACTH does not of gonadotropin. stimulate synthesis of testosterone and dexamethasone does not suppress testosterone secretion, these tumors do not contain receptors for ACTH.

Testosterone secreting adrenal cortical adenomas

Acknowledgement We acknowledge Ann Arthur for technical assistance, Dr. Brij B. Saxena for the gonadotropin assays, and Dr. Cedric Schackleton for gas chromatographic analyses of urinary steroids.

References 1 Burr IM, Graham T, Sullivan J, Hartman WH, O’Neill J:

A testosterone-secreting tumour of the adrenal producing vlrilization in a female infant. Lancet 2: 643, 1973. 2 Werk EE Jr, Sholiton LJ, Kalejs L: Testosterone-secreting adrenal adenoma under gonadotropin control. N Engl J Med 289: 161,1973. 3 Givens JR, Anderson RN, Wiser WL, Coleman SA, Fish S: A gonadotropin-responsive adrenocortical adenoma. J Clin Endocrinol Metab 38: 126,1974. 4 Larson BA, Vanderlaan WP, Judd HI, McCullough DL: A testosterone-producing adrenal cortical adenoma in an elderly woman. J Clin Endocrinol Metab 42: 882, 1976. 5 Check JH, Rakoff AE, Roy BK: A testosterone-secreting adrenal adenoma. Obstet GynecolSI: 46s, 1978. 6 Smith HC, Posen S, Clifton-Bligh P, Casey J: A testosterone-secreting adrenal cortical adenoma. Aust NZ’ J Med 8: 171,1978. I Mack E, Sat-to GE, Crummy AB, Carlson IH, Curet LB, Wu J: Virilizing adrenal ganglioneuroma. JAMA 239; 2213,1978. 8 Takahashi H, Yoshizaki K, KatoH, MasudaT, Matsuka G, Mimura T, Inui Y, Takeuchi S, Adachi H, Matsumoto K: A gonadotrophin-responsive virilizing adrenal tumor identified as a mixed ganglioneuroma and adrenocortical adenoma. Acta Endocrinol89: 701,1978. 9 Schteingart DE, Woodbury MC, Tsao HS, McKenzie AK: Vlrilizing syndrome associated with an adrenal cortical adenoma secreting predominantly testosterone. Am J Med 67: 140,1979. 10 Kable WT, Yussman MA: Testosterone-secreting adrenal adenoma. Fertil Steril32: 610, 1979. 11 DeLange EW, Pratt JJ, Koorenbos H: A gonadotrophin responsive testosterone producing adrenocortical adenoma and high gonadotrophin levels in an elderly woman. Cl Endocrinol12: 21,198O. 12 Spaulding SW, Masuda T, Oswa Y: Increased 17phydroxysteroid dehydrogenase activity in a masculinizing adrenal adenoma in a patient with isolated testosterone overproduction. J Ctin Endocrinol Metab 50: 5 37,198O. 13 Givens R: Hirsutism and hyperandrogenism. In Advances in Internal Medicine (ed GH StoIlerman), p. 221. Year Book Medical Publishers, Chicago, 1976. 14 Braithwaite SS, Erkman-Balis B, Avila TD: Postmeno-

427

pausal vi&ration due to ovarian stromal hyperthecosis. J Clin Endocrinol Metab 46: 295, 1978. 15 Schoneshofer M: Simultaneous determination of eight adrenal steroids in human serum by radioimmunoassay. J Steroid Biochem 8: 995, 1977. 16 Peterson RE, Imperato-McGinley J, Gautier T, Sturla E: Male pseudohermaphroditism due to steroid Sol-reductase deficiency. Am J Med 62: 170, 1977. 17 Mikhail G, Wu CH, Ferin M, Vande Weile RL: Radioimmunoassay of plasma estrone and estradiol. Steroids 1s: 333, 1970. 18 Rommler A, Saxena BB: Separation of antibody-bound and free human follicle stimulating and luteinizing hormones by ethanolammonium acetate. Acta Endocrinol (Kbh) 72: 634,1973. 19 Peterson RE, Wyngaarden JB, Guerra SL, Brodic BB, Bunin JJ: The physiological disposition and metabolic rate of hydrocortisone in man. J Clin Invest 34: 1779, 1955. 20 Peterson RE: Determination of urinary neutral 17-ketosteroid. In Standard Methods in Clinical Chemistry, (ed Seligson) Vol4, p 151. Academic Press, New York, 1963. 21 Abraham GE, Buster JE, Teller RC: Radioimmunoassay of plasma cortisol. Anal Lett J/II): 757, 1972. 22 Hutter AM Jr, Kayhoe DE: Adrenal cortical carcinoma. Am J Med 41: 512,1966. 23 Blichert-Toft M, Vejlsted H, Kehlet H, Albrechsten R: Virilizing adrenocortical adenoma responsive to gonadotrophin. Acta Endocrinol78: 17, 1975. 24 Chakmakhan ZH, Abraham GE: Peripheral steroid levels in a patient with virilizing adrenal adenoma. Obstet Gynecol46: 544,1975. 25 Granoff AB, Abraham GE: Peripheral and adrenal venous levels of steroids in a patient with virillzing adrenal adenoma. Obstet Gynecol.53: 111,1979. 26 Zaitoon MM, Mackie GG: Adrenal cortical tumors in children. Urology 12: 645,1978. 27 Kenny FM, Hashida G, Askari HA, Sieber WH, Fetterman GH: Virilizing tumors of the adrenal cortex. Am J Dis Child 115: 445,1968. 28 David R, August G, Gandy HM: A virihzing adrenal tumor with borderline elevation of urinary Ill-ketosteroids. Pediatrics 42: 139, 1968. 29 Costln G, Goebelsmann U, Kogut MD: Sexual precocity due to a testosterone-producing adrenal tumor. J Clin Endocrinol Metab 45: 912,1977. 30 Siegler RL, Rallison ML: Hypertension with virilizing adrenal tumor. Pediatrics 61: 925, 1978. 31 Lipsett MB: Steroid metabolism and interconversions. In Advances in the Biosciences (ed Raspe G) p 91. Pergamon Press-Viiveg, London, 1969. 32 Osborn RH, Yannone ME: Plasma androgens in the normal and androgenic female: A review. Obstet Gynecol Surv26: 195,197l. 33 Bonaventura LM, Judd H, Roth LM, Cleary RE: Androgen, estrogen, and progestogen production by a lipid cell

Int J Gynaecol Obstet 19

428

Imperato-McGinley et al.

tumor of the ovary. Am J Obstet Gynecol 131: 403, 1978. 34 Imperato-Mffiinley J, Peterson RE, Dawood Y, Zullo M, Kramer E, Saxena BB, Arthur A, Huang T: Gonadal and adrenal steroid secretion from a vi&zing lipoid cell tumor of the ovary in an adult female with a history of precocious puberty. Obstet Gynecol57: 525, 1981.

Int J Gynaecol Obstet 19

Address for reprints: Dr. JuliaMe Imperato-hi&inley Cornell University Medical College 1300 York Avenue New York, NY 10021 USA