A case of ACTH-producing pheochromocytoma associated with pregnancy.
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Ectopic ACTH syndrome is rarely caused by pheochromocytoma. We report a case of a 28-year-old woman with Cushing's syndrome due to ACTH-producing adrenal pheochromocytoma. She had delivered preterm baby at 32nd week of gestation with 'severe preeclampsia'. After delivery, persistent hypertension accompanied by severe headache led her to being misdiagnosed as Cushing's syndrome due to right adrenal adenoma (normal plasma ACTH level) and cerebral vasculitis of unknown etiology. She was referred to our hospital for surgical treatment. Repeated biochemical studies suggested coexistence of ectopic ACTH syndrome and pheochromocytoma. To reverse her clinical deterioration, right total and left subtotal adrenalectomy was performed with presumptive diagnosis of 1) right adrenal pheochromocytoma causing ectopic ACTH syndrome or 2) coexistence of ACTH-dependent Cushing's syndrome and right adrenal pheochromocytoma. Pathologic examination of right adrenal mass revealed pheochromocytoma which showed strong immunostaining for ACTH. Plasma ACTH and urinary cortisol excretion normalized after surgery, but she succumbed to multiple cerebral infarcts and disseminated intravascular coagulation. Pregnancy and inappropriately low plasma ACTH at initial evaluation might have hampered early diagnosis. To our knowledge, this is the first description of a case with ectopic ACTH syndrome due to pheochromocytoma associated with pregnancy. (+info)
Ectopic ACTH syndrome due to thymic atypical carcinoid treated with combination chemotherapy of cisplatin and etoposide.
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A 21-year-old woman with Cushing's syndrome presented with a mediastinal tumor. Ectopic ACTH syndrome was diagnosed and the tumor was resected. The histopathological diagnosis was thymic atypical carcinoid. Despite all tumor lesions having been resected, the tumor relapsed and multiple metastatic lesions grew aggressively. Combination chemotherapy with cisplatin and etoposide (VP16) was administered to control tumor progression, and achieved marked therapeutic effects. Maintenance chemotherapy with carboplatin and VP16 achieved long-term tumor control. This case indicates that some patients with atypical carcinoid tumor are good responders to chemotherapy with platinum agents and VP16. (+info)
Adrenocortical hyperplasia associated with ACTH-dependent Cushing's syndrome: comparison of the size of adrenal glands with clinical and endocrinological data.
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Diffuse or nodular hyperplasia of adrenal glands is associated frequently with ACTH-dependent Cushing's syndrome. We carried out a retrospective analysis of 28 patients with ACTH-dependent Cushing's syndrome admitted to our institution between 1984 and 1999 in order to clarify the incidence of adrenal hyperplasia in ACTH-dependent Cushing's syndrome and also to determine the correlation between adrenal gland images and clinical, biochemical and endocrinological data. Of the 28 patients, 16 (57%) showed diffuse adrenal hyperplasia while only 3 had focal adrenal nodules in the hypertrophied adrenals. There was a positive, significant correlation between the width of the adrenal glands measured on CT and circulating plasma ACTH, cortisol levels and urinary free cortisol (UFC) levels. Duration of the disease also correlated positively with adrenal width. No correlation was found between age and adrenal size and there was no difference in the prevalence of diffuse hyperplasia between normotensive and hypertensive patients. These results suggest that chronic ACTH hypersecretion may lead to diffuse adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome. (+info)
An aberrant ACTH-producing ectopic pituitary adenoma in the sphenoid sinus.
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A 32-year-old woman with an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma (EAPA) is presented. She had rapidly gained weight and suffered recurrent facial acne for a few years but lacked the typical Cushingoid features. Endocrine examinations revealed that her plasma ACTH was markedly high (196 to 280 pg/ml) without showing normal circadian rhythm and failed to respond to corticotropin-releasing hormone stimulation. Her cortisol levels ranged from 22 to 30 microg/dl throughout observation but low doses (1 and 2 mg) of dexamethasone failed to suppress either ACTH or cortisol level. Magnetic resonance imaging study revealed a 3-cm mass occupying the sphenoidal sinus with partial enhancement by gadolinium, which was separated from the normal pituitary in the sella region. The tumor resected by transsphenoidal surgery was histologically diagnosed as an ACTH-producing pituitary adenoma. After surgery her weight gain and acne remitted in accordance with decreases in plasma ACTH. Analysis of patient plasma by gel filtration method revealed the existence of big ACTH molecules eluted with a peak of authentic 1-39 ACTH, suggesting that this biologically less-active ACTH might be the reason why overt features of Cushing's syndrome failed to develop in this case. Although EAPA is clinically rare in parasellar disorders, the presence of ectopic pituitary adenoma should be considered in such cases showing ACTH hypersecretion without typical Cushingoid features. (+info)
Hypomethylation in the promoter region of POMC gene correlates with ectopic overexpression in thymic carcinoids.
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The ectopic ACTH syndrome is caused by abnormal expression of the POMC gene product arising from non-pituitary tumors in response to the ectopic activation of the pituitary-specific promoter of this gene. It has been proved that methylation of the CpG island in the promoter region is associated with silencing of some genes. Using bisulphite sequencing, we identified hypermethylation in the 5' promoter region of the POMC gene in three normal thymuses and one large cell lung cancer, and hypomethylation in five thymic carcinoid tumors resected from patients with ectopic ACTH syndrome. The region undergoing hypermethylation was narrowed to coordinates -417 to -260 of the POMC promoter. Furthermore, we observed that the levels of POMC expression correlated with the methylation density at -417 to -260 bp across the E2 transcription factor binding region of the POMC promoter. It is concluded that hypomethylation of the POMC promoter in thymic carcinoids correlates with POMC overexpression and the ectopic ACTH syndrome. (+info)
RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome.
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OBJECTIVE: ACTH is frequently produced in non-pituitary tumours, leading to the ectopic-ACTH syndrome, but the molecular mechanisms of its expression remain obscure. This study was aimed at understanding the transcription mechanisms of the ACTH-precursor gene in carcinoid tumours of the lung or thymus. DESIGN: Transcripts coding for a series of corticotroph-associated transcription factor genes were detected, together with markers of the corticotroph phenotype. We studied a series of 41 carcinoid tumours including 15 with proven ectopic-ACTH syndrome. METHODS: Specific RT-PCR reactions were designed for each gene including alternatively spliced isoforms. RESULTS: The markers of the corticotroph phenotype were detected in all ACTH-positive tumours. Expression of the Tpit and Pitx1 genes were not restricted to ACTH-positive tumours but were also detected in many ACTH-negative carcinoids. Only a subset of ACTH-negative tumours expressed NAK-1/Nur77, and NeuroD1 expression was detected in approximately 50% of the tumours regardless of their secretory status. The glucocorticoid receptor alpha was detected in every tumour in contrast to its beta isoform detectable in a few tumours only. Chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and peroxisome proliferator-activated receptor (PPAR) gamma2 were expressed in 50% of the tumours of each group whereas PPARgamma1 was expressed in almost every tumour. CONCLUSIONS: ACTH-positive carcinoids do not share a characteristic expression pattern of the corticotroph-associated transcription factor genes, suggesting that the transcriptional mechanisms of the ACTH-precursor gene differ from those in normal pituitary corticotrophs. Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation. (+info)
A 39-year-old woman who presented with typical Cushingoid appearance (moon facies, central obesity, purpura) was admitted to our hospital because of pulmonary infection. She was found to have hypertension, severe hypokalemia, and metabolic alkalosis. Endocrine data revealed elevated plasma levels of ACTH and cortisol with lack of circadian rhythm, non-suppressibility to high-dose dexamethasone, and hyperresponsiveness to CRH stimulation. Although no pituitary mass was detected by MRI of the brain, inferior petrosal sinus sampling showed a step-up of central to peripheral ACTH levels; these data are consistent with the diagnosis of Cushing's disease. She was successfully treated with metyrapone to control hypercortisolemia. Ten months later, a mass was detected in the ethmoid sinus, which was surgically removed. After resection of the ethmoid sinus tumor, her Cushingoid features and hypercortisolemia disappeared, but recurred after enlargement of a second mass in the maxillary sinus. After resection of the maxillary sinus tumor, her hypercortisolemia subsided. Histologically, the tumor tissues from both the ethmoid and maxillary sinus were identical and consistent with the diagnosis of olfactory neuroblastoma. Immunohistochemically, the immunoreactivities of ACTH and POMC were positive in the cytoplasm of tumor cells, and immunoreactive ACTH was demonstrated in both tumor tissues. Thus, this is the second rare case with ectopic ACTH syndrome caused by olfactory neuroblastoma thus far reported. (+info)
Role of adrenalectomy in ectopic ACTH syndrome.
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Evaluation of adrenalectomy in patients diagnosed with ectopic ACTH syndrome was studied. Twenty-three clinical cases diagnosed with ectopic ACTH syndrome were analyzed at Chinese Academy of Medical Sciences and Peking Union Medical College Hospital (PUMCH). Cases consisted of 14 males and 9 females, with mean age of 38 years. All 23 cases had positive clinical, biochemical and radiology evidence for diagnosis of Cushing's syndrome. Sixteen of the 23 cases were treated with total adrenalectomy and the remaining 7 were treated without surgical intervention. Sixteen cases, having no identifiable source of ectopic hormone production, experienced resolution of presenting signs and symptoms after undergoing bilateral or unilateral total adrenalectomy; 1-year survival was 67%, 2-year survival 41% and 5-year survival 15%. In patients treated conservatively without surgical intervention, 1-year survival was 0%. In patients with no identifiable source of ectopic hormone production, bilateral adrenalectomy followed by hormone replacement treatment is effective. (+info)