Androgen secreting adrenocortical tumours

BACKGROUND—Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult.OBJECTIVES—To assess the presentation, histology, and clinical behaviour of these tumours.SETTING—Two tertiary referral centres. Study design—Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996.PATIENTS—Twenty three girls and seven boys aged 0-14 years.RESULTS—Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring < 5 cm in diameter were benign. Of the tumours measuring 5-9 cm, three were malignant and seven were benign, whereas all four tumours > 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen.CONCLUSION—Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.     

Nine cases of childhood adrenal tumour presenting with hypertension and a review of the literature

AIM: To describe the clinical features, treatment and outcome of children adrenal tumors presenting with hypertension. METHODS: The records of nine children under 16 years of age with adrenal tumours presenting with hypertension were analysed. Details were recorded for family history, clinical presentation, biochemistry, imaging, histology, treatment and outcome. RESULTS: Abdominal mass was palpable only in one patient at diagnosis. Besides hypertension-associated symptoms, Cushing's syndrome was the common presentation form (n = 4). Abdominal computed topography showed adrenal mass in all patients. Tumours were completely resected for each patient. The median tumour weight was 73 g (11-530 g) and the size ranged from 1.5 x 1.5 to 12 x 14 cm2. Pheochromocytoma (n = 2), adrenocortical adenoma (n = 3), adrenocortical carcinoma (n = 1), neuroblastoma (n = 2) and ganglioneuromas (n = 1) were found. In one case, adrenal pheochromocytoma first occurred and non-functioning islet cell tumour successively occurred at pancreas. A better status is common at a median follow-up time of 3.5 years. CONCLUSIONS: Childhood adrenal tumours presented with hypertension showed an atypical course, variable presentation. We report a unique case of adrenal pheochromocytoma followed by the occurrence of non-functioning islet cell tumour. Reversal of hypertension by surgery is crucial. Imaging techniques are important to detect adrenal tumours.     

Laparoscopic adrenalectomy in children

PurposeReporting on the laparoscopic technique for adrenal disease in children and adolescents has been limited. We review here our experience with laparoscopic adrenal surgery in children.Patients and methods19 laparoscopic unilateral adrenalectomies were performed in 10 girls and 7 boys (mean age 3.9 years) during 1998–2011. The clinical diagnosis before surgery was virilizing tumor (n = 8), pheochromocytoma (n = 3), nonfunctioning solid adrenal tumor (n = 3), mixed adrenocortical tumor (n = 2), cystic adrenal mass (n = 1). Unilateral adrenal lesions were 20–65 mm at the longest axis on computerized tomography (12 right side, 7 left side).ResultsThe final clinicopathological diagnosis was cortical adenoma (n = 9), pheochromocytoma (n = 3, bilateral in two), neuroblastoma (n = 1), ganglioneuroblastoma (n = 1), ganglioneuroma (n = 1), adrenocortical carcinoma (n = 1), benign adrenal tissue (n = 1). Average operative time was 138.5 min (range 95–270). Blood transfusion was required in one case (5%). No conversion to open surgery was required and no deaths or postoperative complications occurred. Average hospital stay was 3.5 days (range 2–15). Average postoperative follow-up was 81 months (range 2–144). Two contralateral metachronic pheochromocytomas associated with von Hippel-Lindau syndrome occurred, treated with partial laparoscopic adrenalectomy (one without postoperative need of cortisone replacement therapy).ConclusionsLaparoscopic adrenalectomy is a feasible procedure that produces good results. It can be used safely to treat suspected benign and malignant adrenal masses in children with minimal morbidity and short hospital stay.     

Adrenal cortical adenoma in a 13-year-old girl with neurofibromatosis. Case report and review of the literature

We describe the occurrence of an adrenocortical adenoma causing Cushing's syndrome in a 13-year-old girl with neurofibromatosis (NF). Three further cases of adrenocortical tumours in patients with NF have been reported previously, suggesting that there may be an association between NF and tumours of the adrenal cortex.     

Adrenal Cortical Adenoma in a 13-Year-Old Girl with Neurofibromatosis

ABSTRACT. We describe the occurrence of an adrenocortical adenoma causing Cushing's syndrome in a 13-year-old girl with neurofibromatosis (NF). Three further cases of adrenocortical tumours in patients with NF have been reported previously, suggesting that there may be an association between NF and tumours of the adrenal cortex.     

Androgen secreting adrenocortical tumours.

BACKGROUND: Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult. OBJECTIVES: To assess the presentation, histology, and clinical behaviour of these tumours. SETTING: Two tertiary referral centres. STUDY DESIGN: Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996. PATIENTS: Twenty three girls and seven boys aged 0-14 years. RESULTS: Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring < 5 cm in diameter were benign. Of the tumours measuring 5-9 cm, three were malignant and seven were benign, whereas all four tumours > 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen. CONCLUSION: Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.     

Adrenal tumor presenting as precocious puberty

We present a case report of a two and a half-year-old boy who presented with precocious puberty. A clinical diagnosis of congenital adrenal hyperplasia wad made. Patient was investigated and found to have an adrenocortical tumor. The tumor was about 7 cms in diameter. The tumor was secreting androgens, 17OHP and cortisol. This is an unusual array of hormones to be secreted by an adrenal tumor.     

Adrenocortical adenoma in a 2 1/2 year old girl causing virilization and accelerated growth. Clinical and morphological results (author's transl)]

A 2 1/2 year old girl with virilization and advanced bone age was found to have a leftsided adrenocortical adenoma. The secretion of mainly androgens besides estrogens was not suppressible with dexamethasone. Plasma cortisol levels were not elevated but did not show any circadian rhythm. The tumor was localized by retroperitoneal instillation of gas, intravenous urography and tomography. After complete removal of the tumor the originally strongly elevated excretion of 17-ketosteroids sank back to normal, the acceleration of skeletal development slowed down. The right adrenal cortex was not atrophic, 2 1/2 years after the operation the child is well and without evidence of recurrent disease. Differential diagnosis as well as ultrastructor and histology of the tumor are discussed with reference to the literature.     

Hepatic regenerating nodules: a mimic of recurrent cancer in children

Background. Pseudometastatic lesions of the liver may be discovered incidentally in children previously treated for malignant tumour.¶Objective. To describe the radiological pattern of these lesions and to analyse their pathogenesis.¶Materials and methods. Nine children, 2–12 years' old at the time of diagnosis, are described in this retrospective multicentre report. The primary tumours were: nephroblastoma (n = 2), neuroblastoma (n = 2), Ewing's tumour/PNET (n = 2), non-Hodgkin's lymphoma (n = 1), and osteosarcoma (n = 2), treated by surgery (8/9), chemotherapy (9/9), intensive chemotherapy and bone-marrow transplantation (5/9), and radiotherapy (7/9). Three children suffered veno-occlusive disease (VOD) during treatment. The hepatic assessment was performed by sonography (8/9), Doppler (7/9), multiphase spiral CT (8/9) and MRI (7/9).¶Results. Lesions were discovered 15 months to 16 years after completing treatment. CT was the most sensitive modality for diagnosis. Lesions were multiple in eight cases, measured 2–50 mm, and appeared hypervascular on the arterial phase of CT and/or MRI in every case. Metastases were excluded on the basis of histological verification (n = 2) and clinical and radiological follow-up.¶Conclusion. Pseudometastatic hypervascular hepatic nodules can appear after treatment of a malignant tumour in children. The hypothesis of benign regenerative lesions secondary to treatment and/or VOD is considered.     

An adolescent with food-dependent Cushing's syndrome secondary to ectopic expression of GIP receptor in unilateral adrenal adenoma

ACTH-independent Cushing's syndrome may be secondary to the expression of ectopic hormone receptors in adrenal tissue. In food-dependent Cushing's syndrome the adrenals aberrantly express receptors for gastric inhibitory polypeptide (GIP). We present the first case of food- and GIP-dependent adrenal adenoma in an adolescent. A 15 year-old girl presented with signs of hypercortisolism. Urinary cortisol excretion was clearly elevated. Upon the finding of very low fasting plasma cortisol levels with a rise during the morning, food-dependent cortisol secretion was suspected. Hourly measurements of plasma cortisol and GIP levels during a day with and a day without meals showed meal- and GIP-related cortisol secretion. Plasma ACTH levels were undetectable. Abdominal computed tomography showed a tumor of 2.5 x 2.5 x 2 cm in the left adrenal. Unilateral adrenalectomy was performed and microscopic examination of the tumor showed an adrenocortical adenoma. Incubation of adenomatous cells prepared from this tumor with GIP resulted in increased cortisol secretion. Using RT-PCR amplification and cDNA hybridization, the GIP receptor was found to be overexpressed in the adenoma tissue but not in the adjacent adrenal tissue. Twelve months after the operation, hourly measurements of plasma cortisol, GIP and ACTH levels on a day with and a day without meals no longer showed GIP-related cortisol production. The present report shows that in an adolescent with corticotrophin-independent Cushing's syndrome, food-dependent hypercortisolism is a possible diagnosis.     

Adrenal cortical tumours: 25 years' experience at the Royal Children's Hospital, Melbourne

Aims:    Adrenal cortical tumours remain a rare entity with inconsistent consensus about treatment and follow up. This article reviews 25 years of experience in the Royal Children's Hospital, Melbourne, Australia.
Methods:    All records with the diagnosis of adrenal adenoma or carcinoma between 1976 and 2001 were reviewed, excluding tumours of the adrenal medulla. Details were recorded for age, gender, family history, presentation, biochemistry, imaging, histology, diagnosis, treatment and outcome.
Results:    Twelve children (six boys, six girls) were diagnosed with adrenal cortical tumours in this period. Median age at diagnosis was 2.5 years (range 0.5−15.6 years). Six of the 12 children presented with virilization. The remaining six identified by ultrasound performed for hemi-hypertrophy (2), hypertension (2), and fever with abdominal pain (2). Five children had a family history of tumour and two of these five had a p53 mutation demonstrated on molecular genetic analysis. Tumours in five of the 12 children were defined as malignant on histology. Surgery was deemed curative in nine cases. Only one case required further surgery and two required chemotherapy. Time since diagnosis ranged from 1 to 25.8 years. Two children died from complications of the tumour. One other child died following development of a second tumour.
Conclusion:    Adrenal cortical tumours should always be considered in the differential for adrenal hormone excess. New information provided by mutational analysis may predict ongoing risks. Lifelong regular follow up is required.     

Virilising adrenocortical tumours in children

Adrenocortical tumours (ACT) are a rare but important cause of virilisation in infancy and childhood. Four cases of virilising ACT are presented. Two girls (age 0.9 years and 3.9 years) and two boys (age 6.2 years and 6.4 years) had symptoms and signs of virilisation before the age of 6 years. Diagnosis of a virilising adrenal tumour was confirmed by laboratory tests, diagnostic imaging and histology. However, one female patient was misdiagnosed and treated for 3 months as atypical congenital adrenal hyperplasia. Ultrasonography of the adrenal region could not visualise the tumour in three out of four cases. The most sensitive method of diagnostic imaging was MRI. In all cases, treatment consisted of complete surgical resection of the adrenal tumour by open abdominal surgery. Immunohistochemistry was performed in all patients and in two patients there was an overexpression of p53, indicating p53 mutation and in three cases the ki67 proliferation index was greater than 5%. The classification of ACT in childhood is extremely difficult. Histology scores adapted from adrenal tumours in adults and molecular markers are under investigation, but there is still not enough clinical experience since ACT are so rare. CONCLUSION: Long-term follow-up is mandatory not only because of the uncertainty in classification of adrenocortical tumours, but also for observation of growth and pubertal development.     

CUSHING'S SYNDROME IN A THREE MONTH OLD GIRL

This paper describes the rare occurrence of Cushing's syndrome in a female infant aged eleven weeks. An adrenal adenoma was found to be the cause, and its removal was followed by a return to a normal appearance. This patient is the first with this condition seen in this age group at the Royal Children's Hospital since 1948. The Hospital's experience with adrenal tumours since that time is also presented, together with a review of the recent literature.     

Fetal and neonatal liver tumours

Liver tumours are rare in children and account for about 5% of all tumours in the fetus and newborn. The most frequently occurring are benign vascular tumours and mesenchymal hamartomas although malignancy in the form of hepatoblastoma is a possibility. While the diagnosis can be suspected antenatally (by ultrasound and MR scan), a precise diagnosis is often difficult due to the complexity of the tumours. Inutero development of such tumours may be associated with polyhydramnios, fetal hydrops and extreme cases the maternal mirror syndrome. Postnatal symptoms may include abdominal distension, cardiac failure, consumptive coagulopathy and bleeding due to tumour rupture, but is dependent on the nature of the actual tumour. Treatment options may include watchful waiting, surgical resection, hepatic artery embolisation/ligation and chemotherapy.     

Cortisol and estradiol secretion by a benign virilizing adrenocortical tumor in a prepubertal girl

We report a 5.5 year-old girl with a benign adrenocortical adenoma who presented with virilization and rapid growth. She did not have any clinical features of isosexual precocity or, except for hypertension, Cushing's syndrome. Measurement of hormones in adrenal vein blood obtained at surgery showed high concentrations of testosterone, cortisol, estradiol and intermediary substrates. Elevated levels of hormones detected in the peripheral blood were released directly from the tumor and were not the result of peripheral interconversion. Hyperandrogenism can obscure the clinical features of Cushing's syndrome and estrogen hypersecretion in patients with functional adrenal tumors.     

Cushing's syndrome and bronchial carcinoid tumour.

Adrenal function test results in a girl with Cushing''s syndrome and a bronchial carcinoid tumour suggested pituitary dependent hypercortisolism. Resolution after excision of the tumour indicated that her condition had been caused by ectopic adrenocorticotrophic hormone secretion. Conventional tests of adrenal function may be misleading in cases of adrenocorticotrophic hormone secreting bronchial carcinoid tumours.     

Imaging and compartmental classification of solid pelvic tumours in children

Thirty-five children aged from 1 day to 16 years (median 5 years) with solid pelvic tumours were investigated with US, CT and MR. All three methods gave similar estimates of tumour size. For defining location of the tumours, the pelvis was divided into three midline compartments (anterior, middle and posterior) and a right and left lateral compartment. CT and MR were accurate and equally reliable in determining the tumour location, US was less accurate. Evaluation of confinement to organ of origin was uncertain, regardless of imaging modality. Tissue characteristics with CT and MR did not contribute to the differentiation of the various tumour types, and contrast medium enhancemen did not improve the discrimination. Compartmental localization was equally well assessed by CT and MR and, together with sex, was found to correlate with the tumour type.     

Ultrasound computed tomography and magnetic resonance of a neonatal ganglioglioma of the brain

Ganglioglioma is an uncommon nervescell tumour (0,4% of all brain tumours). In 800 brain tumours in children, Garrido et al. (Toronto) found I4 gangliogliomas (1.7%) [1]. To our knowledge, ganglioglioma has not been reported in children under 2½ years of age. We haveincidentally discovered a ganglioglioma in a 3-day-old girl. Appearance on US, CT and MR are described and discussed.     

Adrenocortical Atrophy and Diffuse Cerebral Sclerosis

A boy, diagnosed as having Addison''s disease due to idiopathic atrophy of the adrenal glands at the age of 7 years, developed the first evidence of what was originally thought to be `Schilder''s disease'' at 8 years and 10 months. He died at 9 years and 11 months. There was a very striking family history of autoimmune disorders on the mother''s side. The clinical and pathological aspects of his case are outlined. Detailed studies of adrenal function during life showed a diminution in excretion of adrenal androgens and corticosteroids before therapy which was not evident from the 17-oxosteroid and 17-hydroxycorticosteroid assays in the resting state, though the initial diagnosis was based on the failure of ACTH to produce a rise in the 17-hydroxycorticosteroid excretion. No unusual or abnormal steroids were detected nor was there any disproportion between the androgen and corticosteroid excretion to suggest an adrenal enzyme deficiency. The biochemistry of the brain at necropsy revealed the changes expected in a demyelinating disorder, but the detection of abnormalities in the grey matter distinguished the condition from `Schilder''s disease'' in which the biochemistry of the grey matter is normal. There are 12 fully documented reports of boys with adrenocortical atrophy and diffuse cerebral sclerosis, and it is thought that this rare entity is inherited as an X-linked recessive characteristic. The two likely theories of causation involve either an error of metabolism common to the adrenal cortex and the brain, or the possibility that both the adrenal and brain pathology are due to an autoimmune disorder.     

Adrenal carcinoma and adenoma in children: A review of 17 patients

Seventeen children with adrenocortical neoplasms (13 carcinomas: four adenomas) are reviewed and attention is focused on the value of the newer imaging modalities in the management of these children. All the lesions were functioning tumors. CT is the single most important modality in assessing primary and metastatic disease at diagnosis and during follow-up. In children suspected of having 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 complex echo pattern on ultrasound reflecting the areas of hemorrhage and necrosis seen macroscopically in these lesions. Smaller lesions have a more homogeneous density on CT but benign and malignant disease could not be differentiated by this modality. Ultrasound is useful in screening the adrenal 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.