1/14. Cushing's syndrome secondary to ectopic ACTH secretion from metastatic breast carcinoma.breast carcinoma is a rare cause of ectopic ACTH syndrome. There are only two previously reported cases in which ACTH secretion is documented. We describe the case of a 56-year-old woman who presented with clinical and biochemical features of ectopic ACTH syndrome in the setting of metastatic breast carcinoma. Despite aggressive management of her ectopic ACTH syndrome, her course was complicated by opportunistic infection, respiratory failure and death. Immunostaining of the breast metastases for ACTH was positive and in situ hybridization revealed proopiomelanocortin gene expression. This is the first reported case of ectopic ACTH syndrome associated with metastatic breast cancer in which the technique of in situ hybridization has been used to confirm the breast cancer metastases as the source of ectopic ACTH secretion.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/14. GIP-dependent adrenal Cushing's syndrome with incomplete suppression of ACTH.ACTH-independent Cushing's syndrome may be due to the development of ectopic hormone receptors in adrenal tissue. Thus, in food-dependent Cushing's syndrome the adrenals aberrantly express receptors for gastric inhibitory polypeptide (GIP). We present the case of a 60-year-old woman with food-dependent Cushing's syndrome whose cortisol levels increased after stimulation with CRH. In this patient with Cushing's syndrome the finding of low basal plasma cortisol levels in the late night and early morning as well as a paradoxical rise of plasma cortisol during a 7-h infusion with dexamethasone (carried out without any restriction in food intake), suggested that cortisol production was stimulated at times of food intake. Hourly measurements of plasma cortisol for 48 h revealed prominent meal-related peaks. A plasma cortisol response, elicited by oral glucose administration, could be prevented by octreotide. plasma ACTH was low or undetectable. CRH administration was followed by a ACTH response from 3 to 16 ng/l and a plasma cortisol response from 230 to 680 nmol/l. octreotide treatment for nearly five months induced a partial clinical and biochemical remission. Total bilateral adrenalectomy was performed. The left adrenal was grossly enlarged (7 x 5.5 x 4 cm) and the right adrenal was slightly enlarged (6 x 4 x 1.8 cm). microscopy revealed bilateral nodular hyperplasia. Cell suspensions of adrenal tissue from the patient did respond in a dose-dependent fashion to stimulation with GIP and were very sensitive to stimulation with synthetic ACTH1-24. However, CRH had no significant effect on cortisol production in vitro. Using RT-PCR amplification and cDNA hybridization, GIP receptor was found to be overexpressed in the left and right adrenal tissues from this patient as compared to adrenal tissues from a normal individual or from non GIP-dependent adrenal Cushing's syndrome. There was no evidence of presence of adrenal CRH receptors. Thus, in this patient with food-dependent Cushing's syndrome, the CRH-induced plasma ACTH and cortisol response is probably mediated by an incomplete suppression of the HPA axis as a result of the intermittent food-dependent nature of Cushing's syndrome.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
3/14. Chromosomal aberrations in pituitary carcinoma metastases.Four pituitary carcinoma metastases [two adrenocorticotropic hormone (ACTH) and prolactin cell tumors each] were studied by comparative genomic hybridization. Chromosomal gains were found in all four carcinoma metastases, but losses only in the two prolactin cell carcinoma metastases. overall, pituitary carcinoma metastases showed an average of 8.3 chromosomal imbalances per tumor (7 gains vs 1.3 losses), 10 in prolactin cell carcinoma metastases (7.5 gains vs 2.5 losses) and 6.5 in ACTH cell carcinoma metastases (6.5 gains vs 0 loss). The most common changes were gains of chromosome 5, 7p, and 14q (in three tumors each). High-level gains were found on 13q22-qter and 14q (two cases each) and on 1q, 3p, 7, 8, 9p, and 21q (one case each). To date, gains of chromosome 14q have not been reported among pituitary tumors. It remains to be shown whether gain of 14q is associated with malignant progression and metastatic dissemination of pituitary carcinomas.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
4/14. Corticotroph cell adenoma without typical manifestations of Cushing's disease presenting with cavernous sinus syndrome following pituitary apoplexy.This report presents a unique case of corticotroph cell adenoma in a 30-year-old man without acromegaly or features typical of Cushing's disease, who developed cavernous sinus syndrome following pituitary apoplexy. magnetic resonance imaging revealed a large intrasellar/suprasellar mass with pituitary hemorrhage and extension of a hematoma to the anterior base of the skull. Urgent transnasal pituitary surgery revealed an acidophilic pituitary adenoma, with immunoreactivity for ACTH and GH and expression of proopiomelanocortin (POMC) and GH messenger ribonucleic acid (mRNA) demonstrated by in situ hybridization. To our knowledge, a silent corticotroph cell adenoma with GH production has never been reported. This type of adenoma may potentially enlarge and develop tumoral hemorrhage because it is free of endocrinological symptoms.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
5/14. 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.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
6/14. A case of Cushing's disease caused by pituitary adenoma producing adrenocorticotropic hormone and growth hormone concomitantly: aberrant expression of transcription factors NeuroD1 and Pit-1 as a proposed mechanism.A 53-year-old Japanese woman was diagnosed with Cushing's disease caused by a adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the basis of clinical an imaging data. The surgically resected tumor tissue was investigated histopathologically using immunohistochemical analysis of pituitary hormones. Our study revealed that the adenoma expressed not only ACTH but growth hormone (GH) in the tumor cells. Furthermore, immunohistochemical double staining showed that some adenoma cells were positive for both ACTH and GH. in situ hybridization for GH mRNA revealed that the adenoma cells produced GH as opposed to simply storing it. Although many pituitary adenomas produce multiple pituitary hormones, pituitary adenoma producing both ACTH and GH in the same adenoma cells, such as seen in this case, is extremely rare. To elucidate the molecular mechanism involved, we investigated the expression of transcription factors NeuroD1 and Pit-1 and found that both transcription factors were expressed in many tumor cells. This case report describes a very rare case of pituitary adenoma that produced both ACTH and GH. We propose a hitherto undescribed translineage expression of transcription factors as the basic mechanism of this unique functional differentiation.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
7/14. Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization.Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.- - - - - - - - - - ranking = 3keywords = hybridization (Clic here for more details about this article) |
8/14. Cushing's syndrome due to ectopic proopiomelanocortin gene expression by islet cell carcinoma of the pancreas.Expression of proopiomelanocortin (POMC) was studied in a male patient with Cushing's syndrome and ectopic production of ACTH by a pancreatic carcinoma. plasma ACTH levels (greater than 200 pg/ml) were elevated, and elevated serum cortisol and urinary free cortisol were partially suppressed to 25% of basal levels by high-dose dexamethasone. Petrosal and jugular vein sampling did not yield a gradient of ACTH. Immunohistochemical staining of tumor tissue removed at pancreatectomy was positive for ACTH and beta endorphin, and negative for corticotropin-releasing factor (CRF). Tumor cells cultured in vitro secreted ACTH and beta-endorphin, which comigrated with their respective radiolabeled standards on gel chromatography. hydrocortisone suppressed in vitro ACTH secretion and CRF (100 nM) stimulated ACTH by 50% during 72 hours of incubation. Agarose gel electrophoresis of poly-(A) mRNA extracts of tumor tissue followed by hybridization with 32P-cDNA for POMC revealed 2 distinct rna species. The major rna species (about 1.0 kb) was smaller than authentic pituitary POMC mRNA (about 1.1 kb); a larger precursor band also was visualized, suggesting either processing or degradation of tumor-POMC mRNA. Cytoplasmic dot blot hybridization of tumor mRNA with POMC cDNA yielded a positive signal with increasing amounts of rna blotted. immunohistochemistry and radioimmunoassay (RIA) of ACTH, in vitro regulation of ACTH secretion, and expression of POMC mRNA species by this tumor document expression of the human POMC gene by an islet carcinoma associated with Cushing's syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/14. Characterization of the somatostatin receptor subtype in a bronchial carcinoid tumor responsible for Cushing's syndrome.Small ACTH-secreting carcinoid tumors responsible for Cushing's syndrome are often difficult to localize using available radiological investigations. somatostatin receptors have been found in about 90% of carcinoid tumors studied, leading to a new approach for the localization of tumors or metastasis by using radiolabeled somatostatin analogs. We report a case of Cushing's syndrome due to an ACTH-secreting bronchial carcinoid tumor, completely suppressible with octreotide treatment and evidenced by body scintigraphy with 111In-labeled pentreotide. After removal, which led to patient recovery, the tumor was studied in vitro. in situ hybridization, using a complementary dna probe, revealed POMC messenger ribonucleic acid in a subpopulation of tumor cells. These cells were labeled by immunochemistry using an antiserum directed against ACTH. Confocal laser scanning microscopy analysis showed that the ACTH-immunoreactive peptide was sequestered in secretory granules. Autoradiographic labeling using [125I-Tyrzero,D-Trp8]somatostatin-14 demonstrated the presence of somatostatin-binding sites in the whole tumor tissue. The relative affinities of various selective somatostatin analogs and the ability of GTP to inhibit radioligand binding suggested that the receptor expressed in the tumor cells belonged to the SSTR-2 subtype.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
10/14. ACTH-independent macronodular adrenocortical hyperplasia: immunohistochemical and in situ hybridization studies of steroidogenic enzymes.ACTH independent bilateral macronodular adrenocortical hyperplasia (AIMAH) is associated with autonomous hypercortisolism. We report six cases of AIMAH, in which immunohistochemical studies on steroidogenic enzymes (P450scc, 3 beta HSD, P450c21, P450c17, P450c11) were performed on surgically resected adrenal glands. in situ hybridization studies of P450c17 were performed in two cases in order to localize the sites of steroidogenesis. Immunoreactivity to P450scc, P450c21, and P450c11 was observed in both clear and compact cortical cells, with compact cells displaying more intense staining, as reported in Cushing's adenoma and ACTH dependent bilateral adrenocortical hyperplasia. Immunoreactivity to P450c17 was observed predominantly in small compact cells, whereas that to 3 beta HSD occurred exclusively in clear cortical cells. in situ hybridization also demonstrated that P450c17 was localized in small compact cortical cells. This differential expression of 3 beta HSD and P450c17 in clear and compact cortical cells has been observed only in AIMAH among adrenocortical disorders. This ineffective corticosteroidogenesis may contribute to the relatively low production of cortisol. AIMAH should therefore be considered as a distinct subtype of primary adrenocortical Cushing's syndrome.- - - - - - - - - - ranking = 3keywords = hybridization (Clic here for more details about this article) |
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