Virilizing adrenocortical carcinoma with Cushing’s syndrome in a 14 months old child
S. Garg, M.D., R.K. Marwaha, M.D., I.C. Pathak, F.A.M.S. and R.J. Dash, D.M.
Virilizing adrenocortical carcinoma with Cushing’s syndrome in a 14 month old female child is des- cribed. At operation, tumor infiltration into right renal capsule was noted. The tumor was removed in toto along with the right kidney. The child died a month after due to fecal peritonitis.
Key words: Adrenocortical carcinoma; Cushing’s syndrome.
Cushing’s syndrome in infancy and early childhood is rare and when occurs is invariably caused by adrenocortical car- cinoma. This has been highlighted from studies of Gilbert and Cleveland,1 Green- berg et al,2 and bertagna et al.3 A careful review of Indian literature revealed docu- mentation of only 3 instances.4,6 We describe here one patient of Cushing’s syndrome with virilization in a child of 14 months age.
Case report
J.K. (C.R. No. 532935) F, 14 months of age was referred for evaluation of obesity. Her birth weight was 6.5 lbs and she was reported to have gained weight and became obese over the past 3 months. She had unusually increased appetite. Hypertrichosis and pubic hair appeared at 2 months ago and were growing rapidly in both quantity and
became dark. Facial acne and rosy cheeks were noticed at approximately the same period. She was irritable and had polyuria for the past 6 weeks. She was not known to have diabetes mellitus or hypertension. There was no history of oral or topical steroid therapy.
She was markedly obese with the charac- teristic moon facies (Fig. 1). Her weight was 16.8 kgms (greater than the 97th percentile) length of 94 cms (25th percentile) and blood pressure was 160/110. She had prominent acne vulgaris and a malar flush. She had a very prominent buffale hump. She was plethoric but had no purple striae over the abdomen or thighs. She had hypertrichosis over the lower back, pubic hair grade II-III and enlarged clitoris (3.2 cms). There was prominent secretions of Bartholein’s glands and the labia majora were hypertrophied, rugous and pigmented (Fig. 1). She did not have unusual bruises. Abdominal palpation revealed a firm, smooth, tender lump in the left subcostal region. Liver was not enlarged. Chest, cardiovascular and neurological examination revealed no abnormality. Investigation: Hb 12.1 gm/dl, LTC 15,000/
Departments of Endocrinology, Pediatrics Medicine and Surgery, Postgraduate Institute of Medical Educa- tion and Research, Chandigarh-160 012.
Reprint requests: Prof. R.J. Dash, Head, Departments of Endocrinology.
cmm with P52 L46 E2, platelets were 2,55,000/ cumm. Urine analysis, serum electrolytes, fasting blood sugar, blood urea and detailed biochemical tests for liver functions were normal. Circulating plasma cortisol was elevated, 8 AM 16000 nmol/L, 6PM 1400 nmol/L, with loss of diurnal rhythm and the elevated cortisol was not suppressed (remained 1200 nmol/L) by oral dex- amethasone in a dose upto 20ug/kg body weight administered every 6 h for 2 days. Twenty four hour urinary ketosteroids were 71.4 mg and 82.4 mgms/24h which remained high at 66.8mg/24h following the maximum doses of dexamethasone suppression. Her serum testosterone was 13.5 nmol/L and the
circulating levels of serum gonadotropins, PRL, T4, TSH, T3 were within normal limits. IVP showed a large left suprarenal mass pushing the left kidney downwards and medially (Fig. 2). The mass measured approximately 7 cms in diameter. The right kidney and the urinary tract was normal. Ultrasound of the abdomen confirmed the left suprarenal mass.
Hypertension was controlled by methyl- dopa and chlorthiazide. Preoperatively the child received hydrocortisone 50mg I/M at 6 hour intervals for 2 days. At operation a 6.8 cms well encapsulated yellowish brown left adrenal mass was removed. The left kidney was also removed as the tumor was adherent to its capsule. There were few enlarged
lymph nodes in the paraortic area. The right adrenal gland was palpably small.
The tumor weighed 450 gm. Microscopic examination revealed marked pleomor- phism with increased mitotic figures. The vascular invasion of the tumor cells was also noted. Postoperatively she continued to receive small dosage of anti hypertensives and hydrocortisone 50 mg every 6 h for 5 days and later was put on prednisone orally on gradually reduced dosage. She was dis- charged after the hospital stay of 2 weeks with the advice to continue maintenance steroid therapy. She was brought to the hos- pital a month later with wound dehiscence and fecal fastula and peritonitis. She received cryst penicillin and gentamycin in adequate doses. Her condition however did not improve and she died within 24h of hos- pital stay.
Discussion
Clinical expression of Cushing’s syn- drome in infancy and early childhood dif- fers in several aspects from those in the adults.1,7,8 Generally in the former obesity is massive and generalised with a very promi- nent buffalo hump.1 While the cortisol excess retards axial growth,5 excess of and rogens secreted invariably stimulate growth and induce sexual precocity. The charac- teristic purple striae are generally not seen in infants and small children. Hypertension and proximal myopathy are more frequent. In most instances, the Cushing’s syndrome with virilisation in infancy and childhood is due to adrenocortical carcinoma.2,9,10
The clinical picture of our patient is very classical of functioning adrenocortical car- cinoma with excess of cortisol and androgen secretion. Loss of diurual rhythm in circulat- ing cortisol and lack of maximum dose of dexamethasone suppression supported the
clinical expression of excess cortisol secre- tion. Virilization, pigmented labia majora and increased Bartholein’s gland secretion suggested the excess of androgen secretion. IVP and ultrasonography should be per- formed in all patients with this syndrome, which helps to localise the tumor. Under 15 years of age, adrenal tumors cause Cushing’s syndrome in over 80 percent of the patients.11,12
Distinction between a large benign adrenocortical adenoma from that of an adrenocortical carcinoma is not always easy from the gross or microscopic examination of the tumor. The suggestive features however include: (i) weight of the tumor mass in excess of 300 gm; (ii) infiltration of the tumor tissue to renal capsule; (iii) vas- cular invasion; and (iv) extreme pleomor- phism and increased mitotic figures for the tumor cell nuclei.8,11
Surgery remains the only mode of effec- tive therapy for adrenocortical car- einoma.2,8,10 Where the tumor is inoperable in toto, debulking of the tumor mass, followed by O’p,DDD has been found an acceptable mode of therapy.
The mortality in Cushing’s disease in infants and early childhood has been dis- proportionately high.1,8 High mortality has persisted despite the availability of cor- ticoids. Preoperative preparation of the patient and control of hypertension is essen- tial prior to surgery for good results.
References
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