Adrenocortical Carcinoma in a Child with Congenital Hemi- hypertrophy
S. Ogita1, K. Tokiwa1, T. Takahashi1, A. Kinugasa2, T. Sawada2
1 Division of Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, and 2 Department of Pediatrics, Kyoto Prefectural University of Medicine. Kyoto, Japan
Summary
We describe a very rare case of adreno- cortical carcinoma (ACC) presenting with Cushing’s viril- ising syndrome in a female child with congenital hemi- hypertrophy (CHh). CHh was of more value for early detec- tion of ACC than Cushing’s virilisation.
Key words
Adrenocortical carcinoma - Hemihyper- trophy - Cushing’s syndrome - Virilisation
Adrenokortikales Karzinom bei einem Kind mit kongenitaler Hemihypertrophie
Es wird der seltene Fall eines adrenokorti- kalen Karzinomes mit Cushing-Syndrom vorgestellt. Bei dem Mädchen bestand eine angeborene Hemihypertrophie.
Schlüsselwörter
Adrenokortikales Karzinom - Hemihyper- trophie - Cushing-Syndrom - Virilisation
Introduction
Adrenocortical neoplasms in children are ex- tremely rare (11). In recent years, they have been reported to be associated with congenital hemihypertrophy (CHh), but Haicken et al (7) found only 9 cases in the literature (1, 3, 4, 6, 8, 10, 17, 20) preceding his case reported in 1973. By 1987, 5 more cases had been reported (5, 12, 13, 15, 19) (Table 1).
This report describes a very rare case of adrenocortical carcinoma (ACC) presenting with Cushing’s virilising syndrome in a girl with CHh.
Received February 26, 1988
Z Kinderchir 44 (1989) 166-168
Case report
The girl was born in May 1968, weighing 3100 g af- ter an uneventful pregnancy. She had a normal neonatal course, but en- largement of the left face and arm (asymmetry) was noted by her mother at the age of around 1 year and persisted thereafter. She was noted to be- come obese at the age of around 4 years. At the age of 5 years and 7 months, she was admitted to our hospital with the features of Cushing’s syndrome (buffalo type adiposity, phethoric moon face, growth retarda- tion) and virilisation (pubic hair and hypertrophy of clitoris), and hemi- hypertrophy of left face and arm (Fig. 1).
Except for normal routine laboratory studies, excre- tion of urinary 17-hydroxycorticosteroid (17-OHCS) and urinary 17- ketosteroid (17-KS) were increased (12.6 mg/24 hr and 16.5 mg/24 hr), and the levels of plasma 11-hydroxycorticosteroid (11-OHCS), tes- tosterone and cortisol were also elevated (25.8 ug/dl, 94.0 pg/dl and 22.4 ug/dl, respectively). Administration of 0.5 mg or 2 mg dex- amethasone every six hours did not suppress the serum cortisol level. Excretory urography suggested a right suprarenal tumour. This was confirmed by selective renal arteriography.
At first surgery (at the age of 52/3 years), an encapsu- lated localised suprarenal tumour, measuring 6.0 x 5.0 × 4.0 cm and weighing 114 g, was totally removed. Histological evaluation indicated a high possibility of malignancy. However, the diagnosis of Cushing’s virilising syndrome secondary to the functioning adrenocortical aden- oma in the patient with CHh was made at this time.
After surgery, the findings of an endocrinological dis- order gradually improved to normal.
One year after the first surgery, a palpable right ab- dominal mass and increased accumulation of 131[-19-iodocholesterol in the right suprarenal region suggested the recurrence of the tumour, but endocrinological studies did not show any abnormalities at this time. The patient was left to outpatient follow-up.
At the age of 7 years, enlargement of the right breast was noted, and biopsy of the right breast tissue at the age of 8 years re- vealed an intraductal papilloma on histological examination. At the age of 10 years, a mass in the left breast was noted and the following left mastectomy showed lobular hyperplasia on histological examination. She was lost to follow-up until the age of 13 years and 9 months.
At the second admission, symptoms of Cushing’s syn- drome and features of virilism had almost disappeared, but the hemi- hypertrophy of left face and arm had remained. A right abdominal mass was noted on palpation. Urinary excretion of 17-KS was remarkably el- evated (119.2 mg/24 hr). The value of dehydroepiandrosterone (DHEA) was 75.66 mg/24 hr (more than 50 % of 17-KS). The levels of plasma testosterone, oestradiol and aldosterone were increased, respec tively. A positive response to dexamethasone test was observed. 1311-19- iodocholesterol imaging showed markedly increased accumulation in the right suprarenal region and slightly increased accumulation in the left suprarenal region.
Downloaded by: National University of Singapore. Copyrighted material.
| No. | |Author | Age at DX | Sex | Presenting feature | Hemihyper- trophy | Tumour | Outcome |
|---|---|---|---|---|---|---|---|
| 1 | Harwood (8) | 61/2 yr | M | P | R | R-ACC | Died of disease after 7 months |
| 2 | Riedel (17) | 11 mo | M | P | L | R-AA | Died of second malig- nancy after 5 years |
| 3 | Benson (1) | 41/2 yr | M | P | R | R.ACC | Died of disease a few months later |
| 4 | Copple (3) | 1 yr | F | C | L | L-ACC | Alive, NED for 4 years |
| 5 | Fraumeni (4) | 2 yr | F | P. | R | R-ACC | Alive, for 4 years |
| 6 | Fraumeni (4) | 8 mo | M | C+P | L | R-ACC | Alive, NED for 1 year and 4 months |
| 7 | Grossman (6) | 10 yr | M | C+P | R | R-ACC | Died of disease after 6 months |
| 8 | Loridan (10) | 11 mo | F | C | R | R. L-ACC | Alive, NED for 2 years |
| 9 | Weinstein (20) | 9 mo | F | obesity | L | L-ACC | Alive, NED for 17 months |
| 10 | Haicken (7) | 10 mo | M | n.r. | L | L-ACC | Alive, NED for 1 year |
| 11 | Pfister (15) | 7 yr | M | P | R | R-AA | Alive |
| 12 | Müller (12) | 71/2 yr | F | P | R | R.ACC | Alive, NED for 7 years |
| 13 | Tank (19) | 18 mo | F | C | L | L-ACC | Alive, NED for 15 years |
| 14 | Groff (5) | 17 mo | M | n.r. | R | R-AA | n.r. |
| 15 | Neblett (13) | n.r. | n.r. | Π.Τ. | n.r. | n.r. | n.r. |
| 16 | Our case | 57/12 yr | F | C+P | L | R-ACC | Alive 13 years with disease |
DX, diagnosis; P, precocious puberty: C, Cushing’s syndrome; ACC, adrenocortical carcinoma, AA, adreno- cortical adenoma. n.r., not reported; NED, no evidence of disease
Table 1 Literature review. Adreno- cortical neoplasm and congenital hemihypertrophy.
100
D
50
At the age of 14 years and 2 months, second surgery was performed and an encapsulated right suprarenal tumour, measur- ing 7.0x 5.5×4.5 cm and weighing 102 g, was totally removed. The tu- mour obtained at second surgery was considered to be a malignant ACC
on histological evaluation. It was difficult to observe the left adrenal at laparotomy because of intraabdominal adhesion.
At the age of 17 years and 2 months, she was admit ted again because of a left abdominal tumour. At the age of 18 years and 1 month, the tumour which was in the left adrenal gland, measuring 9.5 × 7.5× 5.5 cm and weighing 178 g, was extirpated during third surgery. Postoperative adrenal imaging, however, showed abnormal accumula- tion at both suprarenal regions.
At the age of 18 years and 9 months, small tumours at both supraadrenal regions were resected and malignancy was con- firmed because of liver metastasis. The histological study confirmed liver metastasis of ACC.
The patient received adjuvant therapy that included 1,1-dichloro-2-(o-chlorophenyl-1)-2-(p-chlorophenyl)ethane (o.p’-DDD) after the third surgery, but it was not effective.
Discussion
Prognosis of ACC is poor and depends on the localisation of the tumour in its originating organ at the initial operation (2, 16). Early detection is necessary so that the ab- dominal tumour can be detected while it is still curative and resectable.
Almost all patients with adrenocortical tu- mours, mean age 4.6 years, presented with endocrine manifesta- tions of the tumour (Cushing’s syndrome, virilisation, or both) (13). Unfortunately, the development of signs and symptoms of endocrine manifestation of the carcinoma may be so insidious that recognition is delayed for weeks to months (9, 13). Indeed, 70 % of functioning adrenal tumours were reported to have in- vasion of adjacent organs or metastases to distant sites at the time of initial operation (2, 18). Therefore, detection of a tu- mour after the development of Cushing’s syndrome, virilisation or both, has not resulted in better prognosis. In our case, the di- agnosis of Cushing’s syndrome was delayed for 11/2 years after
the initial signs, and unfavourable recurrence of the tumour is the result of this delay.
In addition, CHh was noted at the age of around one year in our case, three years prior to the onset of Cushing’s syndrome.
CHh is a very rare condition (4, 20), but it has gained significance in recent years with demonstration of its fre- quent association with childhood tumours (adrenocortical tu- mour, hepatoblastoma and Wilms’ tumour) (1, 4, 5, 7, 12, 14, 15). Haicken et al performed an intravenous pyelogram in the patient with CHh at the age of 10 months with the knowledge of association of CHh and malignancy, and found localised ACC without any associated endocrinopathy, and the outcome was thus favourable (7).
Pfister et al reported that of 9 children with CHh and associated neoplasms, initial recognition of CHh was at birth in 3, at 1 year in 3, at 6 years in 2, and in young adult- hood in one (15). In addition, Haicken et al reviewed that of 9 cases with CHh and adrenocortical tumours, the prognosis of 6 in whom the diagnosis of tumour was made at the age of 1 year or less was better than that of 3 in whom identification was later in childhood although all of the patients presented with symp- toms of endocrinopathy (7).
Therefore, recognition of CHh is of value for an early detection of associated malignancy, especially ACC, in pa- tients with CHh and Cushing’s virilisation, and will improve the prognosis of highly aggressive ACC.
References
1 Benson PF, et al: Congenital hemihypertrophy and malignancy. Lancet 1 (1963) 468-469
2 Cohn K, et al: Adrenocortical carcinoma. Surgery 100 (1986) 1170- 1177
3 Copple PJ, Duncan WY: Congenital hemihypertrophy and adrenal carci- noma. Am J Dis Child 111 (1966) 420
Fraumeri JF, Miller RW: Adrenocortical neoplasms with hemi- hypertrophy, brain tumors, and other disorders. J Pediatr 70 (1967) 129-138
5 Groff DB, Buchino JJ: A child with hemihypertrophy and a right flank mass. J Pediatr 100 (1982) 500-504
6 Grossman H, New M: Precocious sexual development: Roent- genographic aspects. Am J Radiol Radium Ther Nucl Med 100 (1967) 48-62
7 Haicken BN, et al: Adrenocortical carcinoma and congenital hemi- hypertrophy. J Pediatr 83 (1973) 284-285
8 Harwood J, O’Flynn E: Specimens from a case of right-sided hemi- hypertrophy associated with pubertas praecox. Proc R Soc Med 28 (1935) 837-839
9 Henley DJ, et al: Adrenal cortical carcinoma: A continuing challenge. Surgery 94 (1983) 926-931
10 Loridan L, Senior B: Cushing’s syndrome in infancy. J Pediatr 75 (1969) 349-359
11 Miller RW: Peculiarities in the occurrence of adrenal cortical carcinoma. Am J Dis Child 132 (1978) 235-236
12 Müller S, et al: Wilm’s tumor and adrenocortical carcinoma with hemi- hypertrophy and hamartomas. Eur J Pediatr 127 (1978) 219-226
13 Neblett WW, et al: Experience with adrenocortical neoplasms in child- hood. The American Surgeon 53 (1987) 117-125
14 Parker DA, Skalko RG: Congenital asymmetry: report of 10 cases with as- sociated developmental anomalies. Pediatrics 44 (1969) 584-589
15 Pfister RC, et al: Congenital asymmetry (hemihypertrophy) and abdomi- nal disease. Radiology 116 (1975) 685-691
16 Richie JP, Gittes RF: Carcinoma of the adrenal cortex. Cancer 45 (1980) 1957-1964
17 Riedel HA: Adrenogenital syndrome in a male child due to adreno- cortical tumor. Pediatrics 10 (1952) 19-27
18 Stewart DR, et al: Carcinoma of the adrenal gland in children. J Pediatr Surg 9 (1974) 59-67
19 Tank ES, Kay R: Neoplasms associated with hemihypertrophy, Beck- with-Wiedemann syndrome and aniridia. J Urol 124 (1980) 266-268
20 Weinstein RL, et al: Deficient 17-hydroxylation in corticosterone produc- ing adrenal tumor from an infant with hemihypertrophy and viscer. omegaly. J Clin Endocrinol Metab 30 (1970) 457-468
Shuhei Ogita, M.D.
Division of Surgery Children’s Research Hospital Kyoto Prefectural University of Medicine Kyoto-City, 602 Japan