Adrenal carcinoma and adenoma in children: A review of 17 patients
A. Daneman1, Helen S. L. Chan2 and J. Martin1
1Department of Radiology and 2Division of Hematology, The Hospital for Sick Children, and Departments of 1 Radiology and 2Pediatrics, University of Toronto, Toronto, Ontario, Canada
Abstract. Seventeen children with adrenocortical ne- oplasms (13 carcinomas: four adenomas) are re- viewed and attention is focused on the value of the newer imaging modalities in the management of these children. All the lesions were functioning tu- mors. CT is the single most important modality in as- sessing primary and metastatic disease at diagnosis and during follow-up. In children suspected of hav- ing an adrenal lesion, high resolution CT will promptly localize the lesion to an adrenal. Since the only curative treatment is complete surgical removal CT plays an important role in defining the extent of the primary lesion pre-operatively. Large carcinomas have an inhomogeneous density on CT and a com- plex echo pattern on ultrasound reflecting the areas of hemorrhage and necrosis seen macroscopically in these lesions. Smaller lesions have a more homo- geneous density on CT but benign and malignant disease could not be differentiated by this modality. Ultrasound is useful in screening the adreanl area in those patients in whom there is a low clinical index of suspicion for an adrenal tumor and also in the post-operative period.
Key words: Adrenal - Children - Computed to- mography - Ultrasound
Adrenocortical carcinomas and adenomas are ex- tremely uncommon in childhood [15, 20, 22] and ac- counted for 0.3% of all neoplasms at The Hospital for Sick Children, Toronto, in the period 1943 to 1981 inclusive [3].
Children with adrenocortical neoplasms usually have functioning tumours, the clinical presentation being indistinguishable from isosexual or heterosex-
ual precocious puberty due to adrenal hyperplasia or to non-adrenal causes. Even with time consuming and sophisticated hormonal investigations laborato- ry data in these patients are often inconclusive. Thus there is often a delay from the onset of symptoms and signs to the time of the final diagnosis [13, 20, 22].
Radiology plays an important role in the early lo- calization of the primary lesion to the adrenal [15]. Adrenal carcinomas tend to be highly malignant and locally invasive [11, 15]. Since the only curative treat- ment is complete surgical removal, radiology also plays an important role in defining the extent of the primary [15] as well as in assessing the presence or absence of metastatic disease.
The purpose of this paper is to report a large seri- es of childhood adrenocortical carcinomas and ad- enomas from The Hospital for Sick Children, Toron- to. It is our intent to focus attention on the value of the newer imaging modalities in the management of these children as the literature regarding the value of Ultrasound and CT in adrenocortical neoplasms is almost exclusively confined to the experience in adults [1, 4, 5, 10, 14-19, 21].
Materials and methods
Clinical findings
In the 38-year period 1943 to 1981, 17 patients with adrenocortical neoplasms were recorded in the Tumour Registry at The Hospital for Sick Children, Toronto. There were 13 children with carcino- mas. Of these 10 were females and three males. The age range at presentation was 9 months to 17 years with a mean age of approxi- mately 6 years. The remaining four children, all female, had ade- nomas. The age range at presentation was 21/4 years to 61/2 years with a mean of 3.3 years.
All patients had functioning tumours. All of the boys present- ed with pseudo-precocious puberty and the girls with virilization.
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Fig. 1a-c. Calcification on plain abdom- inal radiographs (arrows) a 111/2-year- old girl. Left adrenal carcinoma 16 x 10 x 9 cm diameter. b 11-month old girl. Right adrenal carcinoma 3.5 cm diame- ter. c 41/2-year-old male. Right adrenal carcinoma 7 × 6 × 4 cm diameter
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Only three of the patients with carcinoma presented with cush- ingoid features. Two of the girls (1 carcinoma, 1 adenoma) had feminization and 1 boy with carcinoma had hyperaldosteronism.
In 15 patients the blood pressure was elevated (11 carcinoma: four adenoma). In 11 patients (eight carcinoma: three adenoma) the bone age was advanced. An abdominal mass was palpable in six patients with carcinoma and three of these patients also com- plained of pain.
Laboratory results
In all 16 patients tested (12 carcinoma: four adenoma) the 24-h urinary keto steroid excretion was increased. In 10 patients tested there was no suppression of keto steroid excretion by dexametha- sone administration. Nine patients, all with carcinoma, showed in- creased serum cortisol levels with loss of diurnal variation in only four. In 10 patients (eight carcinoma: two adenoma) tested, the
serum concentration of testosterone and androstenedione were elevated. In one patient serum estradiol concentration was elevat- ed.
Radiographic findings
1) Plain radiographs of the abdomen revealed a soft tissue mass in eight patients (seven carcinoma: one adenoma). Calcification was noted in only three patients - all with carcinoma (Fig. 1).
2) Excretory urography revealed the ipsilateral kidney to be normal in five patients; upper pole flattening or displacement was noted in nine patients and non-function due to invasion of the kidney by an adrenal carcinoma in one (Fig. 2).
3) In 2 patients (one carcinoma: one adenoma) arteriography revealed highly vascular adrenal lesions but did not differentiate benign from malignant disease. In a third patient with a large car- cinoma, arteriography revealed a highly vascular lesion supplied
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by multiple feeding arteries from the diaphragm and posterior ab- dominal wall. In a fourth patient, arteriography suggested the presence of a vascular lesion within the left adrenal. In this patient the diagnosis was confirmed pre-operatively with a positive radi- onuclide iodocholesterol scan.
Venography in only one patient revealed extension of the car- cinoma from the right adrenal into the inferior vena cava.
4) A radionuclide iodocholesterol scan was performed in only one patient in the series and the scan was positive. Technetium MDP was taken up by two lesions (both large carcinomas with calcification and necrosis) on bone scan.
5) CT and ultrasound findings. Eight patients had pre-opera- tive abdominal CT and of these, 3 had pre-operative ultrasound examinations. Five patients had post-operative CT, and three of these patients also had ultrasound to assess the adrenal bed. Two patients had CT on an Ohio Nuclear Delta 50 scanner with a 2- min scan time and the others had CT on a General Electric 8800 with a scan time of 5.7 s. Ultrasound was performed with a Unirad 1000 EDP static scanner and a Technicare Autosector with a 5 mHz transducer.
Pretherapy scans: In three patients with large carcinomas (largest diameter 16 cm, smallest 8 cm) CT and Ultrasound were equally
successful in defining the extent of a primary and intra-abdominal spread. The inferior vena cava was somewhat better visualized with Ultrasound (particularly the real time studies). These three le- sions had an inhomogeneous density on CT and a complex echo pattern on Ultrasound. All three showed calcification on CT (Figs.3 and 6).
In four patients with smaller lesions (two carcinomas, two ad- enomas - largest diameter 6 cm, smallest 1.5 cm) CT revealed the presence of well defined adrenal masses with a more homogene- ous density. The relationship of the lesion to the upper pole of the kidney in two patients (one carcinoma: one adenoma) suggested that the lesion was intrarenal or invading the kidney rather than extrarenal (Figs. 4 and 5).
In one patient a 4.5 cm lesion was not diagnosed at CT - scans were performed with a Delta 50 (2 min scan time). A large amount of motion artifact was present on the study which made detection of the lesion impossible.
Post therapy scans: In one patient with carcinoma CT performed after chemotherapy and radiotherapy showed a reduction in the size of the mass. The relationship of the mass to the great vessels of the abdomen was clearly displayed by scans taken during the intravenous injection of contrast material (Figs.6b and c).
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Five patients had CT and three of these had Ultrasound fol- lowing surgery to assess the adrenal bed. CT and Ultrasound were equally valuable in excluding recurrent lesions in the adrenal bed (Fig.6d).
Spread of carcinoma
In the group of carcinomas at the time of diagnosis, spread in- cluded local invasion -6; lung -4; liver -1; nodal -1; caval -1.
Treatment and outcome
All four patients with adrenal adenoma had complete excision of their tumour and all have survived with no evidence of disease (survival times: 1, 6, 16, 16 years respectively). The adenomatous lesions showed less mitotic activity and less cellular pleomor- phism and were distinguished from carcinomas by having no cap- sular or microvascular invasion.
Twelve of the 13 patients with carcinoma were treated surgi- cally and had all or most of the tumor resected. Seven of these pa- tients and one patient who only had a biopsy of the lesion received post-operative radiation therapy. Four patients also received chemotherapy consisting of O’P-DDD (Mitotane) and/or 5-Flu- orouracil.
Five of the twelve patients who had a total adrenalectomy are still alive between 9 months and 5 years following presentation
and four have no evidence of disease while one patient is alive with pulmonary metastases.
One patient was considered cured but died 19 years following therapy, due to development of a malignant neurilemmoma in the cauda equina in the radiation field. One patient died in the imme- diate post-operative period due to lack of cortisone replacement (1946). The other six patients with carcinoma (including the pa- tient that only had a biopsy) have died between 2 and 12 months following presentation. All had pulmonary metastases. One pa- tient also had extensive local recurrence, and metastatic disease was noted extensively in the abdomen in 1, spine -1, liver -1, and brain -1.
Discussion
Adrenocortical neoplasms have been reported at all ages. The mean age of occurrence is 38 years in males and 28 years in females [15]. Adrenocortical le- sions are rare in the pediatric age group and account for only 0.3% of all neoplasms at The Hospital for Sick Children, Toronto [3]. They are much less com- mon than neuroblastoma but slightly more common than pheochromocytoma.
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The clinical and endocrine findings in the 17 pa- tients reported in this paper are similar to those re- ported in previous series [22]. Carcinoma is much more common than adenoma, the ratio being 3:1 [13, 20, 22]. There was an overall female preponderance (10F:3M in the carcinoma group and all four pa- tients with adenoma were female) [13, 20, 22]. The mean age of presentation for the carcinoma group was approximately 6 years and for the adenoma group 3 years.
All the lesions were functioning tumors and be- nign and malignant disease could not be differentiat- ed on the basis of the endocrine status of the child ei- ther clinically or by hormonal tests. Androgenic ef- fects such as virilization in girls and pseudo-preco-
cious puberty in boys is by far the commonest type of endocrine syndrome seen in patients with adreno- cortical neoplasms and was in fact found in all the patients in this series. Cushing’s syndrome, feminiza- tion, and hyperaldosteronism are much less common [13, 20, 22]. Some of the children in this series had mixed syndromes - a feature of adrenal neoplasms as opposed to hyperplasia which usually produces pure syndromes [13, 20]. Non-functioning adreno- cortical tumors are extremely rare in childhood [10, 20]. The presence of local abdominal symptoms and signs (abdominal mass and pain) was found only in patients with carcinoma.
Differentiation of benign from malignant lesions is difficult with all imaging modalities. The visualiza-
tion of a soft tissue mass on plain abdominal radio- graphs was much more common with carcinomas. Calcification (Fig.1) was seen only in carcinomas [16]; calcification was not related to the size of the carcinoma.
On excretory urography (Fig.2) the ipsilateral kidney remained normal or showed subtle or gross displacement of the upper pole depending on the size of the adrenal lesion [15, 16, 20]. Nonfunction of the kidney due to invasion of the kidney by a carci- noma was the only sign suggesting malignancy and was noted in only one patient.
The clinical presentation of children with adre- nocortical neoplasms is non-specific. Prompt locali- zation of the primary lesion to the adrenal will di- minish the delay from the time of presentation to the time of final diagnosis and hopefully ensure a better survival rate [13, 22].
The smallest lesion in the present series had an average diameter of approximately 2 cm and was easily seen on CT. In previous adult series lesions as small as 0.5 cm have been detected on CT [1, 4, 6]. The relative lack of retroperitoneal fat in children will make the detection of these smaller lesions on CT more difficult. The smallest alteration that we have detected in the adrenal on CT in children is that of adrenal hyperplasia where the glands are general- ly broader than normal. In these patients we were, however, aided in making the diagnosis by the pres- ence of the large amount of retroperitoneal fat due to the Cushing’s syndrome.
Adrenal carcinoma is a highly malignant and lo- cally invasive tumor - extensive local invasion being present in just over 50% of the carcinomas in the present series. Since the only curative treatment is complete surgical removal it is important for the sur- geon to have a good idea of the extent of the lesion preoperatively:
Ultrasound and CT were equally successful in defining the extent of the primary and excluding me- tastatic abdominal disease in the three patients with large carcinomas who were examined with both mo- dalities (Figs.3 and 6). The inferior vena cava was somewhat better seen with ultrasound but its visuali- zation on CT could have been improved had scan- ning been performed during and not after the intra- venous injection of contrast material (Fig.3). These lesions had an inhomogeneous density on CT and a complex echo pattern on ultrasound reflecting the areas of hemorrhage and necrosis seen macroscopi- cally in these large carcinomas.
In the four patients with smaller lesions CT re- vealed the presence of smaller adrenal masses with more homogeneous density but could not differen- tiate benign from malignant disease (Figs.4 and 5).
The relationship of the lesion to the upper pole of the kidney in one patient with a carcinoma and one pa- tient with an adenoma suggested that the lesion was either intrarenal or invading the kidney rather than being totally extrarenal. Although none of these le- sions was studied with ultrasound we believe they would have been detected with this modality and longitudinal scans would probably have resolved the problem of renal invasion.
We believe that any child presenting with endo- crine symptoms or laboratory findings suggesting an adrenocortical neoplasm should have a CT per- formed after the oral ingestion of gastrografin and both before and during intravenous contrast en- hancement. This study should accurately define the site and extent of the primary lesion and display the relationship of the mass to the great vessels of the ab- domen as well as revealing the presence of metastatic disease in lymph nodes or the liver. If a lesion is in fact found in an adrenal in this study a CT scan of the lungs is mandatory. Routine sequential post-op- erative CT of the adrenal bed and chest are impera- tive for accurate follow up.
Although the adrenal may be regularly visualized on ultrasound in neonates we do not believe that ul- trasound will be able to pick up as small a lesion as CT will particularly in the left adrenal. Ultrasound also has the disadvantage that if a lesion is detected the chest cannot be examined at the same examina- tion. Lack of ionizing radiation however makes ul- trasound an ideal modality for screening the adrenal area in those patients in whom there is a low clinical index of suspicion for an adrenal lesion and also for assessing the adrenal bed in the post-operative peri- od.
Angiography, adrenal venography and venous sampling and radioactive I 131-19 iodocholesterol scans may be reserved for those rare patients in whom the CT has not been helpful [9].
Adrenocortical neoplasms have been reported in association with hemihypertrophy, brain tumors and hamartomatous lesions [7] but none of these features were noted in patients in our series.
Acknowledgements. The authors would like to thank Gladys Clarke for typing the manuscript and Dr. Denis Daneman, De- partment of Endocrinology, The Hospital for Sick Children, Tor- onto, for reviewing the manuscript.
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Date of final acceptance: July 28, 1982
Dr. Alan Daneman Department of Radiology The Hospital for Sick Children 555 University Avenue Toronto, Ontario M5G 1X8 Canada