å¡ CASE REPORT å¡ Adrenal Myelolipoma Associated with Congenital Adrenal 21-Hydroxylase Deficiency Chika Murakami, Miyuki Ishibashi, Masahiro Kondo, Sumako Ohshiro, Mutsumi Fujita, Shigenobu Sato, Makoto Kako, Hisashi Furue, Kunio Mizuguchi and Tohru Yamaji* The occurrence of adrenal myelolipomas is reported in an untreated patient with congenital adrenal 21-hydroxylase deficiency. Laparotomy demonstrated the presence of two lesions, a large tumor which arose from an ectopic adrenal cortex and a smaller tumor in the left adrenal gland. Six cases of adrenal myelolipomas and congenital adrenal hyperplasia have been reported in the literature. All patients were associated with excessive ACTH secretion for a long period of time. The relative frequency of this association, coupled with the observation by Selye and Stone (Am J Pathol 26:211, 1950) that anterior pituitary extracts cause myelolipomatous (Internal Medicine 31: 803-806, 1992) changes in rats, may indicate a possible role for ACTH in the development of myelolipomas. Key words: extra-adrenal myelolipoma, congenital adrenal hyperplasia, ACTH
Introduction Myelolipomas of the adrenal gland are benign, non functioning tumors composed of mature adipose cells and hematopoietic elements (1, 2). These tumors are usually small and are discovered incidentally at autopsy with an incidence of less than 0.1% (2). With the advent of newer imaging techniques, the frequency with which Although the pathogenesis myelolipomas remains myelolipomas are clinicallyofdiagnosed is increasing. unclear, prolonged stimulation of the adrenal cortex with adrenocorticotropic hormone (ACTH) may play a causative role. Here we report the occurrence of myelo lipoma in an untreated patient with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Case Report
Virilization, acne, deepening of the voice and muscular development appeared earlier than expected. He was the tallest among his classmates when he was in the lower grades of elementary school, however, his linear growth ceased prematurely by the age of 12. In 1976, the patient was diagnosed as having cholelithiasis and under went cholecystectomy. Although the postoperative course was uneventful and without complications, he began feeling easily tired and weak. Laboratory examination revealed abnormal liver function tests, which lasted to the time of admission with some fluctuations. He was On hishad height was 147cm and weight notadmission, married and no children. 60kg. The blood pressure was 108/78mmHg with a pulse rate of 78/min. There was mild diffuse hyperpig mentation on the lips and over the entire body. Physical examination of the abdomen was negative except for an old operation scar. Laboratory findings were as follows: hemoglobin,
A 41-year-old man was admitted to our hospital in 1990 for investigation of the underlying cause of his long 18.1 g/dl; erythrocyte count, 5,370,000//J; hematocrit, 53.3% ; platelet count, 260,000/^1; and leukocyte count, standing abnormal liver function. There was no family 9,900//il with 53% neutrophils, 9% eosinophils, 1% history of clinically overt endocrine diseases. The patient is the youngest of three children and was the product monocytes, and 37% lymphocytes. Urine evaluation did not show any abnormalities. Serum total protein of a full-term normal delivery. The external genitalia was 7.3g/dl, blood urea nitrogen 8.0mg/dl, creatinine was normally developed at birth. During childhood, the l.Omg/dl, total cholesterol 124mg/dl, glutamic oxalopatient had grown at a more rapid rate than his brother. From the Fourth Department of Medicine and Department of Pathology, Teikyo University School of Medicine, Kawasaki, and *the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo Received for publication November ll, 1991; Accepted for publication February 18, 1992 Reprint requests should be addressed to Dr. Miyuki Ishibashi, the Fourth Department of Medicine, Teikyo University School of Medicine, 7 Mizonokuchi, Takatsu-ku, Kawasaki 213, Japan Internal
Medicine
Vol. 31, No. 6 (June
1992)
803
Murakami et al Table
1.
Endocrine
Function
B a sa l le v e ls P la sm a c o rtiso l O g /d l) P la sm a 17 -h y d ro x y p ro g e ste ro n e (n g /m l) P la sm a A C T H (p g /m l) P la sm a d e h y d ro e p ia n d ro ste ro n e su lfa te (,u g /d l) P la sm a a ld o ste ro n e (n g /d l) U rin a ry 1 7 -h y d ro x y co r tic o ste ro id (m g /d ) U ri n a ry 1 7 -k e to ster o id (m g /d ) A fte r s tim u la tio n w ith 0 .2 5 m g A C T H (1 - 2 4 ) P la sm a c o rtiso l O g /d l) P la sm a 17 -h y d ro x y p ro g e ste ro n e (n g /d m l)
Tests 12 .4 - 1 3 .4 (8 .0 - 1 5 .2 ) 2 0 4 - 32 2 (0 .4 - 2 .0 ) 1 84 (6 - 3 6 ) 3 0 4 (5 3 - 2 5 3) l l (l l - 2 1 ) 4 .0 - 5 .4 (3 .1 - 8 .7 ) 2 2 .7 - 8 8 .2 (4 .2 - 1 2 .4 ) 13 .4 - > 13 .9 3 2 2 -^ 2 9 4
A fte r su p p re ssio n w ith 2 m g /d a y d e x a m e th a so n e fo r 2 d a y s U ri n a ry 17 -h y d ro x y c o rtic o ste ro id (m g /d ) 4 .0 -^ 2 .8 U rin a ry 17 -k e to s te ro id (m g /d ) 8 8 .2 - ^ 14 .2
Numbers in parentheses
indicate
normal ranges
acetic transaminase (GOT) 203 U/l, glutamic pyruvic transaminase (GPT) 294 U/l, y-glutamyl transpeptidase (y-GTP) 210 U/ml, and lactate dehydrogenase 438 U/l. Serum electrolyte values were normal. Antibody for hepatitis C virus was positive. Based on these findings with the hepatic biopsy specimen showing a heavy cellular infiltrate consisting mainly of lymphocytes in the portal zones with piecemeal necrosis of hepatocytes, a diagnosis of chronic active hepatitis due to hepatitis C virus in fection was made. The cause of associated mild poly cythemiaofwas determined. Because hisnot short stature and the presence of mucocutaneous hyperpigmentation, detailed endocrine function tests were performed. He had normal plasma cortisol levels, while plasma 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels were markedly elevated (Table 1). The fluorescence polarization im munoassay for cortisol used in this study did not show a significant cross-reactivity with 17-hydroxyprogesterone or dehydroepiandrosterone sulfate. Plasma ACTH levels also were moderately increased. Although the 24-hour urinary excretion of 17-hydroxycorticosteroid was normal, 17-ketosteroid excretion was definitely increased. An intravenous injection of 0.25 mg ACTH (1-24) failed to increase plasma levels of cortisol or 17 hydroxyprogesterone. Urinary 17-hydroxycorticosteroid and 17-ketosteroid excretion decreased after suppression with 2mg/day of dexamethasone for 2 days. These find ings supported Magnetic resonance the diagnosis imaging of (MRI) congenital of the adrenal abdomen hy perplasia to adrenal 21-hydroxylase deficiency. confirmedsecondary an increase in the size of bilateral adrenal glands, a finding consistent with the diagnosis of con genital adrenal hyperplasia. In addition, a 3 x3cm smooth mass was found in the vicinity of the hilum of the left kidney (Fig. 1). The mass was of heterogeneous signal intensity, with an area of fatty tissue-intensity, and its boundary toward the renal cortex was poorly 804
defined. A renal arteriography suggested the presence of a solid radiolucent hypovascular mass, which may have arisen from the renal capsule. Because malignancy could not completely be excluded, an exploratory laparotomy was performed. At surgery, a dark brown-colored tumor
Fig. 1. Magnetic resonance imaging of the abdomen showing enlarged bilateral adrenal glands and a tumor located in the hilum of the left kidney. RK: right kidney, LK: left kidney, RA: right adrenal gland, LA: left adrenal gland, T: tumor. Internal
Medicine
Vol. 31, No. 6 (June
1992)
Adrenal Myelolipoma
and ACTH
stature of the patient may have resulted from excessive adrenal androgen secretion. MRI of the abdomen incidentally demonstrated a mass in the hilum of the left kidney. The MRI feature of the mass was generally consistent with those seen in myelolipomas (4), however, the lesion was not clearly separable from the adjacent renal cortex. An exploratory laparotomy demonstrated the presence of two lesions, a larger tumor in the hilum of the left kidney and a smaller tumor in the left adrenal gland. Both tumors consisted primarily of proliferating hematopoietic cells and adipose tissue, which fulfilled the diagnostic criterion of myelo lipomas (1, 2). The larger tumor contained adreno variety of mechanisms have been proposed con Fig. 2. Photomicrograph of the larger tumor demonstrating hy A cortical cells suggesting an ectopic adrenal cortex origin. cerning the etiology of adrenal myelolipomas. These perplastic adrenocortical cells with adipose and hematopoietic tissue. include the presence of embryonic bone marrow rests in of 3.0 x 2.4 X 2.5cm in size was located in the hilum of adrenal tissue, establishment of viable areas of bone the left kidney and adherent to the renal cortex. A small, marrow in adrenals by embolization, and metaplasia of similar mass with a yellowish rim measuring 0.4cm in adrenal cortical cells. The most plausible explanation diameter was found in the left adrenal gland. Both may be that fat and hematopoietic elements may be tumors were resected and a biopsy specimen was taken derived from a common progenitor cell in adrenal stroma from the left adrenal cortex. Microscopic examination in response to as yet unknown factors (1). Was congenital revealed that both tumors consisted mainly of mature fat adrenal hyperplasia, then, fortuitously associated with cells and extensive islands of bone marrow elements myelolipomas in our patient? There is a growing body of (Fig. 2). Lymphocytes and lymphoid aggregates with evidence indicating a role of ACTH in the development or without germinal centers were present. In addition, of these adrenal changes. First, review of the literature the larger tumor contained adrenocortical cells. The shows the relative frequency of myelolipomas in patients peripheral yellow rim found in the smaller tumor con associated with excessive ACTH secretion such as con sisted of a layer of adrenal cortex. The biopsy specimen genital adrenal hyperplasia (5-10), Nelson's syndrome from the left adrenal gland showed that hyperplasia of (ll, 12) and Addison's disease (1). To date, 6 cases of the adrenal cortex was primarily at the zone fasciculata. Discussion myelolipomas and congenital adrenal hyperplasia have been reported (5-12) (Table 2). Five of these were In the present report, we document adrenal myelo secondary to adrenal 21-hydroxylase deficiency (5-9), lipomas occurring in an untreated patient with con while in the remaining patient it was secondary to lla genital adrenal hyperplasia due to 21-hydroxylase hydroxylase deficiency (10). Foci of myelolipomatous deficiency. Our patient was normotensive and had lesions were found, in addition, in the hyperplastic adrenal no serum electrolyte abnormality. Although he had glands from 2 patients with adrenal 17ar-hydroxylase normal plasma cortisol levels and normal urinary ex Table 2. Reported of Adrenal Myelolipomas deficiency (13). OfCases extreme importance is that all ofand Congenital Adrenal Hyperplasia (CAH) cretion of 17-hydroxycorticosteroid, plasma levels of these patients were either untreated or had stopped ACTH, 17-hydroxyprogesterone and dehydroepiandro P atients sterone sulfate, and urinary 17-ketosteroid excretion A utho rs S ex A ge T ype of C A H T reatm ent were clearly elevated suggesting that he had partial S chindler (1975) F 53 21-hy droxylase deficien cy un treated impairment of cortisol biosynthesis. As anticipated, B ou dreaux (1979) M 57 2 1-hy droxylase defi cien cy un treated plasma cortisol did not increase after stimulation with B arr (1982 ) F 82 2 1-hy droxylase defi cien cy un treated ACTH. Plasma 17-hydroxyprogesterone also failed to O liva (1988) F 34 2 1-hy droxylase deficien cy M iyazak i (1990) F 65 2 1-hy droxylase deficien cy un treated respond to ACTH, as is generally observed in patients P resent stu dy M 4 1 2 1-hy droxylase deficien cy un treated with adrenal 21-hydroxylase deficiency with elevated C on dom (1985) F 50 17-hy droxylase deficien cy un treated basal plasma 17-hydroxyprogesterone levels (3). Urinary 17-hydroxycorticosteroid and 17-ketosteroid were sup * This patient was treated with glucocorticoid until puberty, when she stopped taking all medications, and was lost to follow-up for 20 years pressed by low-dose dexamethasone. All these findings support the diagnosis of adrenal 21-hydroxylase de Internal Medicine Vol. somatic 31, No. development 6 (June 19VZ) and short 805 ficiency. Premature
Murakami et al medication long before, which suggests that excessive ACTH secretion lasted for 20 years or longer. Further, myeloid metaplasia in the adrenal cortex was observed in severely burned patients and cancer patients, who were subject to long periods of intense stress (14). Second, Selye and Stone induced myelolipomatous adrenal masses in rats by injection of crude anterior pituitary extracts (15). Testosterone also caused transformation of adrenal cortical precursor cells into mature fat cells and this effect was enhanced by simultaneous administration of anterior pituitary extracts. In view of these findings, it is likely that the excessive ACTH secretion over a long period of time in the present patient had a stimulatory Whether or not ACTH may be a major factor responsible role in the development of the adrenal myelolipomas. for the development of adrenal myelolipomas should be clarified in future studies by demonstrating ACTH receptors in myelolipoma, on one hand, and by reaf firming the higher incidence of myelolipomas in patients with excessive ACTH secretion by use of new imaging techniques, on the other. An understanding of the pathogenesis of myelolipomas may help to identify the unknown mechanisms that control adrenocortical dif ferentiation and proliferation. Finally, myelolipomas are clinically benign, and cli nicians should be aware of this presentation to avoid unnecessary radical operation. Since, as in the pre sent patient, myelolipomas arise from extra-adrenal locations and the frequent use of newer imaging tech niques will facilitate more frequent discovery of asymp tomatic lesions, myelolipomas should be considered in the differential diagnosis of any radiolucent mass con taining fat-density tissues (4).
806
References 1) Plaut A. Myelolipoma in the adrenal cortex. Am J Pathol 34: 487, 1958. 2) Olsson CA, Krane RJ, Klugo RC, Selikowitz SM. Adrenal myelolipoma. Surgery 73: 665, 1973. 3) New MI, Lorenzen F, Lerner AJ, et al. Genotyping steroid 21 hydroxylase deficiency: hormonal reference data. J Clin Endo crinol Metab 57: 320, 1983. 4) Musante F, Derchi LE, Zappasodi F, et al. Myelolipoma of the adrenal gland: Sonographic and CT features. Am J Roentgenol 15: 961, 1988. 5) Schindler H. Myelolipom der Nebenniere bei adrenogenitalem Syndrom. Wien Med Wochenschr 125: 695, 1975 (in German). 6) Boudreaux D, Waisman J, Skinner DG, Low R. Giant adrenal myelolipoma and testicular interstitial cell tumor in a man with congenital 21-hydroxylase deficiency. Am J Surg Pathol 3: 109, 1979. 7) Barr AB, Giltman LI. Congenital adrenal hyperplasia diagnosed in an 82-year-old: Case report. Virginia Med 109: 844, 1982. 8) Oliva A, Duarte B, Hammadeh R, Ghosh L, Baker RJ. Myelo lipoma and endocrine function. Surgery 103: 711, 1988. 9) Miyazaki Y, Yoshida M, Doi J. A case of adrenal myelolipoma associated with adrenogenital syndrome. Acta Urol Jpn 36: 35,1990. 10) Condom E, Villabona CM, Gomez JM, Varrera M. Adrenal myelolipoma in a woman with congenital 17-hydroxylase defi ciency. Arch Pathol Lab Med 109: 1116, 1985. ll) Maschler I, Rosenmann E, Ehrenfeld EN. Ectopic functioning adrenocortico-myelolipoma in longstanding Nelson's syndrome. Clin Endocrinol 10: 493, 1979. 12) Bennett BD, McKenna TJ, Hough AJ, Dean R, Page DL. Adrenal myelolipoma associated with Cushing's disease. Am J Clin Pathol 73: 443, 1980. 13) Sasano H, Masuda T, Ojima M, Fukuchi S, Sasano N. Con genital 17
Introduction Myelolipomas of the adrenal gland are benign, non functioning tumors composed of mature adipose cells and hematopoietic elements (1, 2). These tumors are usually small and are discovered incidentally at autopsy with an incidence of less than 0.1% (2). With the advent of newer imaging techniques, the frequency with which Although the pathogenesis myelolipomas remains myelolipomas are clinicallyofdiagnosed is increasing. unclear, prolonged stimulation of the adrenal cortex with adrenocorticotropic hormone (ACTH) may play a causative role. Here we report the occurrence of myelo lipoma in an untreated patient with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Case Report
Virilization, acne, deepening of the voice and muscular development appeared earlier than expected. He was the tallest among his classmates when he was in the lower grades of elementary school, however, his linear growth ceased prematurely by the age of 12. In 1976, the patient was diagnosed as having cholelithiasis and under went cholecystectomy. Although the postoperative course was uneventful and without complications, he began feeling easily tired and weak. Laboratory examination revealed abnormal liver function tests, which lasted to the time of admission with some fluctuations. He was On hishad height was 147cm and weight notadmission, married and no children. 60kg. The blood pressure was 108/78mmHg with a pulse rate of 78/min. There was mild diffuse hyperpig mentation on the lips and over the entire body. Physical examination of the abdomen was negative except for an old operation scar. Laboratory findings were as follows: hemoglobin,
A 41-year-old man was admitted to our hospital in 1990 for investigation of the underlying cause of his long 18.1 g/dl; erythrocyte count, 5,370,000//J; hematocrit, 53.3% ; platelet count, 260,000/^1; and leukocyte count, standing abnormal liver function. There was no family 9,900//il with 53% neutrophils, 9% eosinophils, 1% history of clinically overt endocrine diseases. The patient is the youngest of three children and was the product monocytes, and 37% lymphocytes. Urine evaluation did not show any abnormalities. Serum total protein of a full-term normal delivery. The external genitalia was 7.3g/dl, blood urea nitrogen 8.0mg/dl, creatinine was normally developed at birth. During childhood, the l.Omg/dl, total cholesterol 124mg/dl, glutamic oxalopatient had grown at a more rapid rate than his brother. From the Fourth Department of Medicine and Department of Pathology, Teikyo University School of Medicine, Kawasaki, and *the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo Received for publication November ll, 1991; Accepted for publication February 18, 1992 Reprint requests should be addressed to Dr. Miyuki Ishibashi, the Fourth Department of Medicine, Teikyo University School of Medicine, 7 Mizonokuchi, Takatsu-ku, Kawasaki 213, Japan Internal
Medicine
Vol. 31, No. 6 (June
1992)
803
Murakami et al Table
1.
Endocrine
Function
B a sa l le v e ls P la sm a c o rtiso l O g /d l) P la sm a 17 -h y d ro x y p ro g e ste ro n e (n g /m l) P la sm a A C T H (p g /m l) P la sm a d e h y d ro e p ia n d ro ste ro n e su lfa te (,u g /d l) P la sm a a ld o ste ro n e (n g /d l) U rin a ry 1 7 -h y d ro x y co r tic o ste ro id (m g /d ) U ri n a ry 1 7 -k e to ster o id (m g /d ) A fte r s tim u la tio n w ith 0 .2 5 m g A C T H (1 - 2 4 ) P la sm a c o rtiso l O g /d l) P la sm a 17 -h y d ro x y p ro g e ste ro n e (n g /d m l)
Tests 12 .4 - 1 3 .4 (8 .0 - 1 5 .2 ) 2 0 4 - 32 2 (0 .4 - 2 .0 ) 1 84 (6 - 3 6 ) 3 0 4 (5 3 - 2 5 3) l l (l l - 2 1 ) 4 .0 - 5 .4 (3 .1 - 8 .7 ) 2 2 .7 - 8 8 .2 (4 .2 - 1 2 .4 ) 13 .4 - > 13 .9 3 2 2 -^ 2 9 4
A fte r su p p re ssio n w ith 2 m g /d a y d e x a m e th a so n e fo r 2 d a y s U ri n a ry 17 -h y d ro x y c o rtic o ste ro id (m g /d ) 4 .0 -^ 2 .8 U rin a ry 17 -k e to s te ro id (m g /d ) 8 8 .2 - ^ 14 .2
Numbers in parentheses
indicate
normal ranges
acetic transaminase (GOT) 203 U/l, glutamic pyruvic transaminase (GPT) 294 U/l, y-glutamyl transpeptidase (y-GTP) 210 U/ml, and lactate dehydrogenase 438 U/l. Serum electrolyte values were normal. Antibody for hepatitis C virus was positive. Based on these findings with the hepatic biopsy specimen showing a heavy cellular infiltrate consisting mainly of lymphocytes in the portal zones with piecemeal necrosis of hepatocytes, a diagnosis of chronic active hepatitis due to hepatitis C virus in fection was made. The cause of associated mild poly cythemiaofwas determined. Because hisnot short stature and the presence of mucocutaneous hyperpigmentation, detailed endocrine function tests were performed. He had normal plasma cortisol levels, while plasma 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels were markedly elevated (Table 1). The fluorescence polarization im munoassay for cortisol used in this study did not show a significant cross-reactivity with 17-hydroxyprogesterone or dehydroepiandrosterone sulfate. Plasma ACTH levels also were moderately increased. Although the 24-hour urinary excretion of 17-hydroxycorticosteroid was normal, 17-ketosteroid excretion was definitely increased. An intravenous injection of 0.25 mg ACTH (1-24) failed to increase plasma levels of cortisol or 17 hydroxyprogesterone. Urinary 17-hydroxycorticosteroid and 17-ketosteroid excretion decreased after suppression with 2mg/day of dexamethasone for 2 days. These find ings supported Magnetic resonance the diagnosis imaging of (MRI) congenital of the adrenal abdomen hy perplasia to adrenal 21-hydroxylase deficiency. confirmedsecondary an increase in the size of bilateral adrenal glands, a finding consistent with the diagnosis of con genital adrenal hyperplasia. In addition, a 3 x3cm smooth mass was found in the vicinity of the hilum of the left kidney (Fig. 1). The mass was of heterogeneous signal intensity, with an area of fatty tissue-intensity, and its boundary toward the renal cortex was poorly 804
defined. A renal arteriography suggested the presence of a solid radiolucent hypovascular mass, which may have arisen from the renal capsule. Because malignancy could not completely be excluded, an exploratory laparotomy was performed. At surgery, a dark brown-colored tumor
Fig. 1. Magnetic resonance imaging of the abdomen showing enlarged bilateral adrenal glands and a tumor located in the hilum of the left kidney. RK: right kidney, LK: left kidney, RA: right adrenal gland, LA: left adrenal gland, T: tumor. Internal
Medicine
Vol. 31, No. 6 (June
1992)
Adrenal Myelolipoma
and ACTH
stature of the patient may have resulted from excessive adrenal androgen secretion. MRI of the abdomen incidentally demonstrated a mass in the hilum of the left kidney. The MRI feature of the mass was generally consistent with those seen in myelolipomas (4), however, the lesion was not clearly separable from the adjacent renal cortex. An exploratory laparotomy demonstrated the presence of two lesions, a larger tumor in the hilum of the left kidney and a smaller tumor in the left adrenal gland. Both tumors consisted primarily of proliferating hematopoietic cells and adipose tissue, which fulfilled the diagnostic criterion of myelo lipomas (1, 2). The larger tumor contained adreno variety of mechanisms have been proposed con Fig. 2. Photomicrograph of the larger tumor demonstrating hy A cortical cells suggesting an ectopic adrenal cortex origin. cerning the etiology of adrenal myelolipomas. These perplastic adrenocortical cells with adipose and hematopoietic tissue. include the presence of embryonic bone marrow rests in of 3.0 x 2.4 X 2.5cm in size was located in the hilum of adrenal tissue, establishment of viable areas of bone the left kidney and adherent to the renal cortex. A small, marrow in adrenals by embolization, and metaplasia of similar mass with a yellowish rim measuring 0.4cm in adrenal cortical cells. The most plausible explanation diameter was found in the left adrenal gland. Both may be that fat and hematopoietic elements may be tumors were resected and a biopsy specimen was taken derived from a common progenitor cell in adrenal stroma from the left adrenal cortex. Microscopic examination in response to as yet unknown factors (1). Was congenital revealed that both tumors consisted mainly of mature fat adrenal hyperplasia, then, fortuitously associated with cells and extensive islands of bone marrow elements myelolipomas in our patient? There is a growing body of (Fig. 2). Lymphocytes and lymphoid aggregates with evidence indicating a role of ACTH in the development or without germinal centers were present. In addition, of these adrenal changes. First, review of the literature the larger tumor contained adrenocortical cells. The shows the relative frequency of myelolipomas in patients peripheral yellow rim found in the smaller tumor con associated with excessive ACTH secretion such as con sisted of a layer of adrenal cortex. The biopsy specimen genital adrenal hyperplasia (5-10), Nelson's syndrome from the left adrenal gland showed that hyperplasia of (ll, 12) and Addison's disease (1). To date, 6 cases of the adrenal cortex was primarily at the zone fasciculata. Discussion myelolipomas and congenital adrenal hyperplasia have been reported (5-12) (Table 2). Five of these were In the present report, we document adrenal myelo secondary to adrenal 21-hydroxylase deficiency (5-9), lipomas occurring in an untreated patient with con while in the remaining patient it was secondary to lla genital adrenal hyperplasia due to 21-hydroxylase hydroxylase deficiency (10). Foci of myelolipomatous deficiency. Our patient was normotensive and had lesions were found, in addition, in the hyperplastic adrenal no serum electrolyte abnormality. Although he had glands from 2 patients with adrenal 17ar-hydroxylase normal plasma cortisol levels and normal urinary ex Table 2. Reported of Adrenal Myelolipomas deficiency (13). OfCases extreme importance is that all ofand Congenital Adrenal Hyperplasia (CAH) cretion of 17-hydroxycorticosteroid, plasma levels of these patients were either untreated or had stopped ACTH, 17-hydroxyprogesterone and dehydroepiandro P atients sterone sulfate, and urinary 17-ketosteroid excretion A utho rs S ex A ge T ype of C A H T reatm ent were clearly elevated suggesting that he had partial S chindler (1975) F 53 21-hy droxylase deficien cy un treated impairment of cortisol biosynthesis. As anticipated, B ou dreaux (1979) M 57 2 1-hy droxylase defi cien cy un treated plasma cortisol did not increase after stimulation with B arr (1982 ) F 82 2 1-hy droxylase defi cien cy un treated ACTH. Plasma 17-hydroxyprogesterone also failed to O liva (1988) F 34 2 1-hy droxylase deficien cy M iyazak i (1990) F 65 2 1-hy droxylase deficien cy un treated respond to ACTH, as is generally observed in patients P resent stu dy M 4 1 2 1-hy droxylase deficien cy un treated with adrenal 21-hydroxylase deficiency with elevated C on dom (1985) F 50 17-hy droxylase deficien cy un treated basal plasma 17-hydroxyprogesterone levels (3). Urinary 17-hydroxycorticosteroid and 17-ketosteroid were sup * This patient was treated with glucocorticoid until puberty, when she stopped taking all medications, and was lost to follow-up for 20 years pressed by low-dose dexamethasone. All these findings support the diagnosis of adrenal 21-hydroxylase de Internal Medicine Vol. somatic 31, No. development 6 (June 19VZ) and short 805 ficiency. Premature
Murakami et al medication long before, which suggests that excessive ACTH secretion lasted for 20 years or longer. Further, myeloid metaplasia in the adrenal cortex was observed in severely burned patients and cancer patients, who were subject to long periods of intense stress (14). Second, Selye and Stone induced myelolipomatous adrenal masses in rats by injection of crude anterior pituitary extracts (15). Testosterone also caused transformation of adrenal cortical precursor cells into mature fat cells and this effect was enhanced by simultaneous administration of anterior pituitary extracts. In view of these findings, it is likely that the excessive ACTH secretion over a long period of time in the present patient had a stimulatory Whether or not ACTH may be a major factor responsible role in the development of the adrenal myelolipomas. for the development of adrenal myelolipomas should be clarified in future studies by demonstrating ACTH receptors in myelolipoma, on one hand, and by reaf firming the higher incidence of myelolipomas in patients with excessive ACTH secretion by use of new imaging techniques, on the other. An understanding of the pathogenesis of myelolipomas may help to identify the unknown mechanisms that control adrenocortical dif ferentiation and proliferation. Finally, myelolipomas are clinically benign, and cli nicians should be aware of this presentation to avoid unnecessary radical operation. Since, as in the pre sent patient, myelolipomas arise from extra-adrenal locations and the frequent use of newer imaging tech niques will facilitate more frequent discovery of asymp tomatic lesions, myelolipomas should be considered in the differential diagnosis of any radiolucent mass con taining fat-density tissues (4).
806
References 1) Plaut A. Myelolipoma in the adrenal cortex. Am J Pathol 34: 487, 1958. 2) Olsson CA, Krane RJ, Klugo RC, Selikowitz SM. Adrenal myelolipoma. Surgery 73: 665, 1973. 3) New MI, Lorenzen F, Lerner AJ, et al. Genotyping steroid 21 hydroxylase deficiency: hormonal reference data. J Clin Endo crinol Metab 57: 320, 1983. 4) Musante F, Derchi LE, Zappasodi F, et al. Myelolipoma of the adrenal gland: Sonographic and CT features. Am J Roentgenol 15: 961, 1988. 5) Schindler H. Myelolipom der Nebenniere bei adrenogenitalem Syndrom. Wien Med Wochenschr 125: 695, 1975 (in German). 6) Boudreaux D, Waisman J, Skinner DG, Low R. Giant adrenal myelolipoma and testicular interstitial cell tumor in a man with congenital 21-hydroxylase deficiency. Am J Surg Pathol 3: 109, 1979. 7) Barr AB, Giltman LI. Congenital adrenal hyperplasia diagnosed in an 82-year-old: Case report. Virginia Med 109: 844, 1982. 8) Oliva A, Duarte B, Hammadeh R, Ghosh L, Baker RJ. Myelo lipoma and endocrine function. Surgery 103: 711, 1988. 9) Miyazaki Y, Yoshida M, Doi J. A case of adrenal myelolipoma associated with adrenogenital syndrome. Acta Urol Jpn 36: 35,1990. 10) Condom E, Villabona CM, Gomez JM, Varrera M. Adrenal myelolipoma in a woman with congenital 17-hydroxylase defi ciency. Arch Pathol Lab Med 109: 1116, 1985. ll) Maschler I, Rosenmann E, Ehrenfeld EN. Ectopic functioning adrenocortico-myelolipoma in longstanding Nelson's syndrome. Clin Endocrinol 10: 493, 1979. 12) Bennett BD, McKenna TJ, Hough AJ, Dean R, Page DL. Adrenal myelolipoma associated with Cushing's disease. Am J Clin Pathol 73: 443, 1980. 13) Sasano H, Masuda T, Ojima M, Fukuchi S, Sasano N. Con genital 17
