1/24. growth hormone isoforms in a girl with gigantism.Several previous investigations have suggested that there may be different growth hormone isoforms in patients with acromegaly. We used three different site-specific monoclonal antibodies (MAbs) to investigate growth hormone (GH) isoforms in serum from an 8 year-old girl with a GH and prolactin secreting adenoma. The pattern of GH-immunoreactivity was dependent on the circumstances of collection. serum obtained after oral glucose had very little cross reactivity with MAb 352 although concentrations of up to 15 micrograms/l were found with two other MAbs, 033 and 665. MAb 352 does not recognize the 20,000 dalton isoform of GH (20K) while both MAb 033 and 665 do. The same pattern of GH immunoreactivity (low MAb 352, equal and higher MAb 033 and 665) was seen in other baseline samples. In contrast, samples obtained after TRH/GnRH showed immunoreactivity patterns expected for a mixture of 22,000 dalton isoform of GH (22K) with only a small amount of 20K. GH samples obtained during sleep showed both patterns with episodic peaks with equal immunoreactivity superimposed on the basal pattern (decreased activity with MAb 352). Affinity chromatography of basal samples showed that a portion of the GH immunoreactivity was neither 22K nor 20K, although in stimulated samples, over 70% of GH was 22K or 20K GH. In conclusion, the nature of GH isoforms present in serum varies with GH concentration. These differences may contribute to the known difficulty in correlating disease activity and random GH measurements in patients with GH secreting adenomas.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/24. adrenal insufficiency after incomplete resection of pituitary macrocorticotropinoma of Cushing's disease: role of high molecular weight ACTH.A 15-year-old girl with Cushing's disease exhibited adrenal insufficiency following incomplete trans-sphenoidal resection of a large pituitary corticotropinoma, approximately 35 mm in diameter. Within two weeks following surgery, her plasma ACTH level decreased from 42 to 13 pmol/l, while, her plasma cortisol levels and urinary excretion of free cortisol decreased from 607 nmol/l and 1112 nmol/day to 94 nmol/l and 55 nmol/day, respectively. Immunoreactive ACTH was characterized in plasma using Sephadex G-75 column chromatography and measuring ACTH with immunoradiometric assay (IRMA) and radioimmunoassay (RIA) to determine additional peaks, other than the one demonstrated for 1-39 ACTH. In particular, when measured with RIA, a broad peak including the high molecular weight ACTH was detected as well as 1-39 ACTH. The bioactivity of the high molecular weight ACTH in patient plasma was lower than the reference range of 1-39 ACTH, which is determined by the ability of dispersed rat adrenocortical cells to secrete corticosterone. The large pituitary corticotropinoma found in this patient secreted not only 1-39 ACTH but also high molecular weight proopiomelanocortin (POMC)-derived peptides, which could be detected by measuring with IRMA and RIA for ACTH. Based on the results of biological activity and molecular ratios, no positive evidence could be found to support the hypothesis that the high molecular weight ACTH induced any postoperative adrenal insufficiency in this patient. However, based on this study, the possibility of adrenal insufficiency should be carefully monitored, even when post-operative remnant tumor tissue is clearly present in patients with Cushing's disease, accompanied by macrocorticotropinoma.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/24. Significant gene expression of insulin-like growth factor ii and proliferating cell nuclear antigen in a rapidly growing recurrent pituitary acth-secreting adenoma.BACKGROUND: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurred very rapidly as invasive macroadenoma. methods/RESULTS: A 43-year-old woman underwent successful transsphenoidal surgery for Cushing's disease. Seven years later, she was admitted to our ward for further endocrine examinations. In spite of a very high plasma ACTH level, the serum cortisol level was normal. Discrepancies between ACTH and cortisol levels were detected on the basis of diurnal rhythms, dexamethasone suppression tests, and corticotropin-releasing hormone test. The patient showed no clinical features of Cushing's disease. magnetic resonance imaging of the pituitary showed an almost empty sella, and no microadenoma was found. These results, along with those of Sephadex column gel filtration and high-performance liquid chromatography of plasma-immunoreactive ACTH, suggested that the patient's residual corticotrophs secreted biologically inactive ACTH. Two years later, the patient suddenly developed diplopia and right abducens nerve palsy. She was slightly moonfaced and centrally obese. Her plasma ACTH and serum and urinary free cortisol levels were elevated, although discrepancies between ACTH and cortisol still existed. magnetic resonance imaging revealed a large pituitary mass with suprasellar and cavernous sinus extensions. The tumor was excised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region of the proopiomelanocortin gene. A significant expression of insulin-like growth factor II and proliferating cell nuclear antigen mRNAs was demonstrated. A high MIB-1 antibody labeling index was also detected in the adenoma tissue, suggesting high Ki-67 expression. CONCLUSION: These growth- and proliferation-related factors might be involved in the rapid growth and aggressiveness of this patient's pituitary adenoma.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/24. Pitfalls in pituitary diagnosis: peculiarities of three cases.Due to the increasing availability and sensitivity of diagnostic methods, biochemical and imaging abnormalities of pituitary function and anatomy are becoming more frequent. Hyperprolactinaemia was found in three women without any prolactin (PRL) related clinical features. All three patients had normal libido, regular menses with evidence of ovulation, no galactorrhoea, and normal FSH, LH, TSH and free T4 serum levels. magnetic resonance imaging (MRI) of the sellar region showed images that were compatible with pituitary microadenomas in all three cases. Due to the discordance between laboratory and clinical features, we searched for the presence of PRL aggregates with high molecular weight and low biological activity (macroprolactinaemia). Initially, we screened with a polyethylene glycol precipitation method, and then confirmed the presence of macroprolactinaemia by chromatography. All three cases screened positive for the presence of macroprolactinaemia. MRI alterations, compatible with pituitary microadenomas, may be due to true microincidentalomas, normal anatomical variations or imaging artefacts. In conclusion, we have described the presence of double diagnostic pitfalls that might lead to unnecessary medical or surgical intervention.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/24. Secretion of high-molecular-weight adrenocorticotropic hormone from a pituitary adenoma in a patient without Cushing stigmata. Case report.The authors report a case in which a patient harbored a corticotroph macroadenoma that secreted biologically inactive high-molecular-weight adrenocorticotropic hormone (ACTH) as well as authentic ACTH 1-39. The secretion of the high-molecular-weight ACTH was determined using gel chromatography. The authors believe that these two molecules competed with each other at the ACTH receptor and, thus, the bioactivity of ACTH 1-39 was masked and Cushing features were not manifested in the patient. This type of silent corticotroph adenoma may be categorized as a clinically nonfunctioning adenoma. Plasmas from patients with silent corticotroph adenomas, which are identified by positive immunohistochemical staining of ACTH, should be frozen, stored, and analyzed using gel chromatography to examine whether the tumors produce and secrete high-molecular-weight ACTH.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
6/24. Endocrine, biochemical, and morphological studies of a pituitary adenoma secreting growth hormone, thyrotropin (TSH), and alpha-subunit: evidence for secretion of TSH with increased bioactivity.A 40-yr-old man who had acromegaly and hyperthyroidism due to a GH/TSH-secreting pituitary adenoma is described. serum free T4 was 2.8 ng/dl, free T3 was 1.1 ng/dl, and TSH was 1.2-1.5 microU/ml; the latter was measured in an immunoradiometric assay with a sensitivity of 0.07 microU/ml. serum TSH was immunologically identical to standard TSH and did not decrease during a T3 suppression test. serum free alpha-subunit and the molar alpha-subunit to TSH ratio were high (6.1 ng/ml and 31.2, respectively). TRH administration induced significant increases in both GH ( 129%) and alpha-subunit ( 156%) levels. Conversely, dopamine infusion resulted in a decrease in serum GH (-66%) and alpha-subunit (-43%) levels, and subsequent administration of the dopamine antagonist sulpiride induced significant increases in both GH and alpha-subunit ( 393% and 106%, respectively). Similarly, somatostatin infusion inhibited GH (-43%) and alpha-subunit (-61%) secretion. serum TSH levels were not affected by TRH, dopamine, or somatostatin. The biological to immunological activity ratio of serum TSH purified by immunoaffinity chromatography and measured in an adenylate cyclase assay was significantly increased compared to that in serum from hypothyroid or euthyroid subjects [biological to immunological activity ratio, 6.9 /- 0.2 ( /- SD) vs. 4.4 /- 1.1; P less than 0.001]. In gel chromatography, the apparent mol wt of the patient's TSH was smaller than that of the controls. After adenomectomy, all of the altered parameters of pituitary function became normal. Double gold particle immunostaining of the adenomatous tissue showed that all of the cells contained secretory granules positive for GH and alpha-subunit, while very few cells were positive for TSH beta as well as GH and alpha-subunit. These data indicate that in this patient serum TSH had an apparent mol wt smaller than that of normal TSH and an increased biological activity which, along with the autonomous TSH secretion, account for hyperthyroidism in the presence of low normal TSH levels; alpha-subunit originated from the same adenomatous cells that secreted GH but not TSH, thus explaining the in vivo observation that alpha-subunit responses to several agents were dissociated from TSH responses and parallel to GH responses; and TSH and GH were colocalized in a minority of the neoplastic cells.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
7/24. A case of multiple endocrine neoplasia (MEN) type 1; the immunohistochemical and ultrastructural studies of its tumors and the analysis of hormones in tumor extracts.We reported a case of sporadic multiple endocrine neoplasia type 1, with multiple insulinoma, parathyroid adenoma, and pituitary tumor. Measurement of hormone contents and immunohistochemical studies of the pancreatic tumors showed that the tumors contained insulin, glucagon, somatostatin, and pancreatic polypeptide. Furthermore, the concentrations of these hormones were different in each tumor. Insulin extracted from the pancreatic tumors analyzed by reversed-phase high performance liquid chromatography revealed no structural abnormalities. On the other hand, in gel filtration evaluation of the extract of the parathyroid adenoma, it was found that the tumor extract contained a macromolecular parathyroid hormone (molecular weight 20,000 to 25,000).- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
8/24. A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing's disease.We report a patient with hypersecretion of a high mol wt ACTH from an aggressive corticotropic pituitary tumor who did not have hypercortisolism. Basal plasma ACTH levels were clearly elevated (26-121 pmol/L), whereas basal and stimulated serum cortisol levels were in the normal range. The pituitary source of the ACTH hypersecretion was confirmed by selective venous catheterization. Gel chromatography of the patient's plasma showed two peaks of ACTH immunoreactivity, one major peak eluting near the void volume (high mol wt form of ACTH), accounting for more than 95% of the ACTH detected, and a very small peak at the expected position of ACTH-(1-39). plasma ACTH levels were not altered by metyrapone or bromocriptine. During high dose dexamethasone administration plasma ACTH decreased, but was not fully suppressed. Immunohistochemical evaluation of tumor tissue demonstrated ACTH immunoreactivity in 40% of the tumor cells. The patient died from postoperative complications after a second operation performed after tumor recurrence. This patient's course confirms the observations of relatively rapid growth and high recurrence rate in clinically silent corticotropic pituitary adenomas.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
9/24. dopamine in paragangliomas of the glomus jugulare.Glomus jugulare tumors have the ability to synthesize, store, and secrete biogenic amines. Although the majority of these tumors remain endocrinologically silent, on rare occasions they present either as a pheochromocytoma or with a carcinoid syndrome. We report a 20-year-old male with two intracranial tumors: an intrasellar neoplasm and a glomus jugulare tumor. Catecholamine catabolites in the urine were not increased, and blood pressure was always normal. The pituitary tumor was an adenoma, immunostaining positive for prolactin. The second patient, a 29-year-old hypertensive male, with a glomus jugulare tumor, had increased vanillylmandelic-acid excretion. In both cases, the paraganglioma tumor cells contained numerous dense-core vesicles (125 to 380 nm in diameter) in electron microscopy, and showed intense fluorescence by the sucrose-potassium phosphate-glyoxylic acid method. Using high-performance liquid chromatography and microspectrofluorometry we were able to establish the presence of large amounts of dopamine in the cytoplasm of the tumor cells.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/24. Gonadotropin-secreting pituitary adenoma with concomitant hypersecretion of testosterone and elevated sperm count. Treatment with LRH agonist.Hypersecretion of both FSH and LH was demonstrated in a man with pituitary macroadenoma, who also presented elevated levels of blood testosterone and an increased sperm count. The patient underwent transsphenoidal surgery followed immediately by cranial irradiation. Immunocytochemical analysis of the tumour revealed the presence of FSH, LH, TSH and the alpha-subunit. Gel chromatography of the serum on Sephadex G-100 revealed immunoactive FSH, LH and the alpha-subunit which coeluted with the labelled standards of corresponding hormones. Blood levels of both gonadotropins and testosterone remained persistently elevated up to one year following surgical decompression of the tumour and radiotherapy. It was decided to treat this patient with sc administration of 100 micrograms D-Trp6-LRH biweekly. After 20 weeks, LRH-analogue treatment resulted in the reduction of serum FSH and LH levels and a diminishing in tumour size as assessed by computed tomography scan of the pituitary. This report shows that in a patient with clinically and biochemically documented gonadotropin-secreting adenoma, inducing a state of persistent gonadal hyperfunction, pituitary surgery and cranial irradiation failed to normalize the biochemical abnormality; however, therapy with D-Trp6-LRH agonist induced clinical, biochemical and radiologic improvement.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
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