RESUMO
BACKGROUND: To evaluate the levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in cervicovaginal secretions before and after midtrimester amniocentesis and relate to clinical outcome. METHODS: 100 consecutive amniocentesis procedures were studied. We measured the IGFBP-1 concentration by radioimmunoassay in a cervicovaginal specimen before and after mid-trimester amniocentesis. The post-amniocentesis occurrence of vaginal loss of fluid or blood and abdominal pain was assessed by questionnaire. RESULTS: In 6 cases there was a 100-fold increase in IGFBP-1 levels after amniocentesis. Loss of fluid per vaginam occurred in 4 (67%) of these pregnancies, compared to 3.2% of pregnancies without significant surge (p < 0.0001). In addition, post-procedural abdominal pain was more common among women with increased IGFBP-1 levels after amniocentesis (50 vs. 14%, p = 0.05). Two (33%) of the 6 patients with increased IGFBP-1 after amniocentesis delivered prior to 37 weeks as a result of spontaneous preterm labor and/or preterm ruptured membranes, compared to 7 (7%) in the group without surge in IGFBP-1 (p = 0.09). CONCLUSION: Increased post-procedure IGFBP-1 levels are after mid-trimester amniocenteses are related to procedure-related complications like abdominal pain and subsequent amniotic fluid leakage.
Assuntos
Amniocentese/métodos , Colo do Útero/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Feminino , Ruptura Prematura de Membranas Fetais/diagnóstico , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , GravidezRESUMO
UNLABELLED: The effect of age and vitamin D status on parathyroid function was studied in 129 healthy subjects between 20 and 89 yr old, with normal serum creatinine (less than 0.11 mmol/L), and living in Cordoba, Spain. Serum calcium and phosphorus as well as 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] decreased, whereas serum alkaline phosphatase increased, with age. Serum PTH also increased significantly with age when measured with either a carboxyl-terminal (cPTH) or an intact [PTH(1-84)] assay. The increase in cPTH, however, exceeded largely the increase in PTH(1-84) (+120% and +30% in subjects above 80 yr vs. young adults, respectively). Serum PTH(1-84) was negatively correlated with serum (ionized) calcium, 25OHD, and insulin-like growth factor I (IGF-I) but not with serum 1,25-(OH)2D. Serum 1,25-(OH)2D decreased with age and was highly correlated with serum 25OHD, cPTH, and IGF-I. In multiple regression analysis 50-60% of the variation of total and free 1,25-(OH)2D could be explained by serum 25OHD, PTH(1-84), and especially IGF-I, suggesting a possible role of decreasing GH and IGF-I concentrations in the mineral homeostasis of the elderly. Calcium infusion (1.5 mg/kg body weight over 10 min) decreased serum PTH(1-84) to below normal concentrations in young adults (nadir 14% of basal concentration), whereas the nadir in elderly subjects with secondary hyperparathyroidism was only 32% of basal concentration. The relative decrease was, however, identical in both age groups when simultaneous changes in ionized calcium were taken into account. Basal serum PTH(1-84) in selected elderly subjects (50 +/- 10 ng/L or 5 +/- 1 pmol/L, n = 10) decreased significantly (2.7 +/- 0.9 pmol/L, P less than 0.01) after 3 iv injections of 1,25-(OH)2D during 1 week without changes in serum (ionized) calcium. The PTH suppressibility after calcium infusion did not further improve. IN CONCLUSION: elderly patients with normal serum creatinine had a small (+30%) but significant increase in intact serum PTH concentration but the mean concentration still remained within the normal range. The PTH secretion remained normally suppressible by acute calcium infusion. Treatment with 1,25-(OH)2D decreased basal calcium-PTH setpoint without further additional effects during calcium infusion.
Assuntos
Envelhecimento/fisiologia , Glândulas Paratireoides/efeitos dos fármacos , Vitamina D/farmacologia , Adulto , Idoso , Cálcio/farmacologia , Estudos Transversais , Di-Hidroxicolecalciferóis/sangue , Feminino , Humanos , Hidroxicolecalciferóis/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/fisiologia , Hormônio Paratireóideo/sangueRESUMO
We tested the hypothesis of whether chromogranin-A (CGA), an immunohistochemical marker of neuroendocrine tumors, could serve as a serum marker for clinically nonfunctioning pituitary adenomas. Basal and TRH-stimulated concentrations of LH, FSH, alpha-subunit, and CGA were measured in 22 patients with clinically nonfunctioning pituitary adenomas and in 20 control patients with other pituitary tumors. The control group consisted of 9 patients with PRL- and/or GH-secreting adenomas and 11 patients with nonendocrine tumors [5 craniopharyngiomas, 2 (dys)germinomas, 1 astrocytoma, 1 meningioma, 1 neurinoma of the acoustic nerve, and 1 dermoid cyst]. Immunohistochemical staining for CGA was performed on tumor tissue obtained at transsphenoidal surgery in 18 study and 12 control patients. Tissue from 19 of the 22 clinically nonfunctioning adenomas was cultured, and concentrations of LH, FSH, alpha-subunit, and CGA were measured. Immunohistochemical staining for CGA was positive in 15 of 18 clinically nonfunctioning adenomas and negative in all examined control tumors (n = 12). CGA was present in the culture medium of 16 of 18 adenomas in vitro. In 3 adenomas it was present in the absence of detectable amounts of gonadotropins or alpha-subunit. Basal serum levels of gonadotropins and/or alpha-subunit were elevated in 7 of 22 patients with clinically nonfunctioning adenomas and in 4 of 9 control patients with PRL- and/or GH-secreting adenomas. Basal CGA was elevated in 2 study patients and 1 prolactinoma patient. Significant increases in serum gonadotropin and/or alpha-subunit levels in response to TRH occurred in 14 of 21 patients with clinically nonfunctioning adenomas and in 13 of 20 control patients. A significant CGA peak after TRH administration was demonstrated in 6 patients with clinically nonfunctioning pituitary tumors and in none of the controls. We conclude that 1) immunohistochemical staining for CGA is an excellent tool to prove the endocrine origin of clinically nonfunctioning pituitary tumors; 2) in vivo, the gonadotroph origin can be recognized in only a minority of patients who have elevated basal levels of LH, FSH, or alpha-subunit; 3) examination of the effect of TRH on CGA release is a rather insensitive, but specific, diagnostic test, allowing differentiation from nonendocrine pituitary tumors; and 4) the responses of gonadotropins and alpha-subunit to TRH, although more sensitive, are not specific for clinically nonfunctioning pituitary adenomas and are probably only reliable in cases of total hypopituitarism.
Assuntos
Adenoma/diagnóstico , Cromograninas/sangue , Gonadotropinas Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico , Hormônio Liberador de Tireotropina , Adenoma/química , Adenoma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromogranina A , Cromograninas/análise , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Subunidade alfa de Hormônios Glicoproteicos/sangue , Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Humanos , Imuno-Histoquímica , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/metabolismo , Células Tumorais CultivadasRESUMO
Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use.
Assuntos
Biomarcadores Tumorais/sangue , Cromograninas/sangue , Subunidade alfa de Hormônios Glicoproteicos/sangue , Tumores Neuroendócrinos/sangue , Fosfopiruvato Hidratase/sangue , Adulto , Idoso , Tumor Carcinoide/sangue , Carcinoma Medular/sangue , Carcinoma de Células Pequenas/sangue , Cromogranina A , Diagnóstico Diferencial , Feminino , Gastrinoma/sangue , Humanos , Ácido Hidroxi-Indolacético/urina , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Tumores Neuroendócrinos/diagnóstico , Neoplasias da Glândula Tireoide/sangueRESUMO
We evaluated whether measuring serum levels of chromogranin A, a marker of neuroendocrine tumours, could be useful in the differential diagnosis between pituitary, adrenal and ectopic causes of Cushing's syndrome. Thirty patients with Cushing's syndrome were studied. The localization of the tumours responsible was pituitary in 15, adrenal in 5 and ectopic in 10 patients. Serum concentrations of chromogranin A were measured in all patients. Petrosal sinus sampling for chromogranin A was performed in the cases with pituitary-dependent Cushing's syndrome. Immunohistochemical staining for chromogranin A was carried out on part of the tumour specimens. Slightly elevated serum levels of chromogranin A (range 223-262 micrograms/l) were detected in inferior petrosal sinus and peripheral venous samples from three patients with pituitary-dependent Cushing's syndrome. Serum chromogranin A showed no significant pituitary to peripheral gradient in these patients. Chromogranin A levels were not elevated in cases of adrenal Cushing's syndrome. Markedly elevated concentrations (range 270-13,900 micrograms/l) were shown in seven of 10 patients with neuroendocrine tumours with ectopic adrenocorticotrophin (ACTH) and/or corticotrophin-releasing hormone (CRH) production. Widespread metastasis was present in all these cases. Subjects with "occult" carcinoid tumours, with limited spread, had normal chromogranin A levels. Immunohistochemical staining for chromogranin A was positive in three out of five pituitary adenomas and in all neuroendocrine tumours with ectopic ACTH and/or CRH production, while it was negative in all adrenocortical tumour specimens. It is concluded that elevated serum levels of chromogranin A can serve as markers of neuroendocrine tumours with ectopic ACTH and/or CRH production.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cromograninas/sangue , Síndrome de Cushing/sangue , Síndrome de Cushing/diagnóstico , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Cromogranina A , Hormônio Liberador da Corticotropina/farmacologia , Síndrome de Cushing/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/metabolismo , Coloração e RotulagemRESUMO
In this immunoradiometric assay (IRMA) of parathyrin (PTH) a polyclonal anti-amino-PTH(1-34) is the capture antibody and a radiolabeled monoclonal anti-hPTH(44-68) is the second antibody. Gel filtration of serum from a hyperparathyroid patient yielded only a single peak of PTH, corresponding to the elution position of synthetic PTH(1-84). Healthy elderly individuals (ages 78 +/- 5 y, mean +/- SD, n = 45) had PTH concentrations (21 +/- 13 ng/L) not significantly higher than those from healthy younger (38 +/- 11 y) adults (20 +/- 8 ng/L, n = 94). Assay results agreed well with those obtained with a carboxyl-terminal PTH assay both in normal subjects (r = 0.63, P less than 0.001) and in patients with primary hyperparathyroidism (r = 0.59, P less than 0.001). Both assays equally discriminated patients with surgically confirmed primary hyperparathyroidism from normal individuals, but the PTH(1-84) IRMA also allowed a nearly absolute discrimination between normal subjects and patients with primary hypoparathyroidism (undetectable serum PTH in 18 of 21 cases) and secondary hypoparathyroidism (caused by hypercalcemia that was caused by a malignant tumor, PTH 1.3 +/- 1.3 ng/L, n = 32). Moreover, the PTH(1-84) IRMA is more sensitive (detection limit in serum, 0.8 ng/L) and easier and quicker to perform than the carboxyl-terminal assay.
Assuntos
Anticorpos Monoclonais , Epitopos/análise , Hormônio Paratireóideo/sangue , Adulto , Idoso , Cromatografia em Gel , Diagnóstico Diferencial , Feminino , Humanos , Hiperparatireoidismo/sangue , Hipoparatireoidismo/sangue , Ensaio Imunorradiométrico , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Valores de ReferênciaRESUMO
Previous data suggested that small for gestational age newborns have increased levels of IGF binding protein 1 (IGFBPI) in amniotic fluid (AF) at 15-16 wk of pregnancy. In this study, we developed an RIA for IGFBP1 and measured IGFBP1 concentrations in 209 AF samples with normal fetal karyotype between 14 and 20 wk; we measured IGF-I, IGF-II, and C-peptide in the same samples. Concentrations of these growth-modulating factors were all positively correlated with gestational age at sampling (p < 0.0001). After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester. None of the growth-modulating factors in AF correlated with birth weight, after correction for gestational age; birth weight percentile distribution was comparable in two groups of newborns who had AF values of IGF-I, IGF-II, IGFBP1, or C-peptide that were either less than or equal to the 50th percentile or more than the 50th percentile at sampling. However, placenta weight and the placenta weight to birth weight percentage were negatively correlated with AF IGF-I, IGF-II, and IGFBP1; placenta weight to birth weight percentage was lower in pregnancies with IGFBP1 values more than the 50th percentile compared with those less than or equal to the 50th percentile at sampling. In conclusion, AF concentrations of IGFBP 1 increase gradually between 14 and 20 wk gestational age and correlate with IGF-I and IGF-II levels; high IGFBP1 levels do not predict small for gestational age newborns, but are associated with lower placenta weight.