RESUMO
The precise molecular abnormalities that cause primary cortisol resistance have not been completely described. In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone. We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance. Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced. At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729. When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding, the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM (mean +/- SEM) (P < 0.01), respectively. When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity. The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject.
Assuntos
Resistência a Medicamentos/genética , Hidrocortisona/fisiologia , Mutação Puntual , Receptores de Glucocorticoides/genética , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Criança , Chlorocebus aethiops , DNA/genética , Dexametasona/metabolismo , Feminino , Humanos , Rim , Cinética , Leucócitos Mononucleares/metabolismo , Masculino , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Reação em Cadeia da Polimerase/métodos , RNA/genética , RNA/isolamento & purificação , Receptores de Glucocorticoides/metabolismo , TransfecçãoRESUMO
The binding of (+/-)-[7-3H]isoproterenol to intact chicken erythrocytes has been investigated by a rapid centrifugation technique. The binding is displaceable by a one thousand-fold excess of cold isoproterenol and consists of two fractions, only one of which is inhibitable by the beta antagonist (--)-propranolol. The total displaceable binding to intact cells amounts to 80 or 127 molecules per cell at a (+/-)-isoproterenol concentration of 0.4 muM depending on the method employed to analyze the binding. Under similar conditions, the total displaceable binding to isolated membrane ghosts is 12600 molecules per cell. The propranolol-inhibitable binding to intact cell reaches saturation within 5 min at 4 degrees C and gives by scatchard analysis a maximum binding of 108 molecules per cell and with a KD of 0.4 muM. 50% inhibition of binding is obtained with 0.3 muM unlabeled (--)-isoproterenol as compared to 20 muM unlabeled (+)-isoproterenol. The binding of isoproterenol thus shows a marked stereospecific preference for the (--)-isomer.
Assuntos
Membrana Celular/metabolismo , Eritrócitos/metabolismo , Isoproterenol/sangue , Receptores de Superfície Celular , Animais , Sítios de Ligação , Ligação Competitiva , Proteínas Sanguíneas/metabolismo , Membrana Celular/efeitos dos fármacos , Galinhas , Cinética , Propranolol/farmacologia , Ligação Proteica , Receptores de Superfície Celular/efeitos dos fármacosRESUMO
Generalized inherited glucocorticoid resistance is a rare disorder caused by glucocorticoid receptor mutations and characterized clinically by hypercortisolism. Pituitary and peripheral resistance are balanced so that neither adrenal insufficiency nor Cushingoid features develop. Clinical characteristics reflect overproduction of adrenal androgens and mineralocorticoids, which are caused by excess stimulation of the adrenal gland by ACTH. These clinical characteristics respond to dexamethasone therapy. Localized and/or acquired glucocorticoid resistance may occur in some circumstances.
RESUMO
A novel putative mediator of insulin action which acts to inhibit adenylate cyclase and cAMP-dependent protein kinase has been purified from livers of insulin-treated streptozotocin-diabetic rats. It was increased by short term (5-min) insulin injections in vivo and purified several thousand-fold by Sephadex and HPLC. Its mol wt was somewhat larger (2500) than previous mediators identified, and it was more hydrophobic in character. Its mechanism of action or adenylate cyclase was determined and found to be chiefly directed against the catalytic subunit. Its action on the cAMP-dependent protein kinase was found to be competitive with regard to protein substrate, but noncompetitive with regard to ATP and cAMP. Its relationship to other putative insulin mediators and the mechanism of insulin action is discussed.
Assuntos
Inibidores de Adenilil Ciclases , AMP Cíclico/farmacologia , Diabetes Mellitus Experimental/metabolismo , Fosfatos de Inositol , Insulina/farmacologia , Fígado/análise , Polissacarídeos , Inibidores de Proteínas Quinases , Receptor de Insulina/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Ligação Competitiva , Cromatografia Líquida de Alta Pressão , AMP Cíclico/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Cinética , Fígado/efeitos dos fármacos , Masculino , Camundongos , Ratos , Ratos Endogâmicos , Receptor de Insulina/isolamento & purificaçãoRESUMO
Aldosterone secretion in man is stimulated by potassium (K), ACTH, and angiotensin II (AII) and inhibited by dopamine (DA). In normal sodium-replete supine individuals, aldosterone secretion is under maximum tonic inhibition by DA and is not inhibited further by DA administration. Sodium depletion alters plasma aldosterone responses to secretogogues. Upright posture, another physiological stimulus to aldosterone secretion, recently was demonstrated to sensitize the adrenal cortex to inhibition of aldosterone secretion by a large quantity of DA (4.0 micrograms/kg X min). The effect of upright posture on aldosterone responses to other secretogogues is unknown. In this study, we investigated the effect of upright posture on aldosterone responses to low infusion rates of DA, to the DA antagonist metoclopramide (M) and to AII and ACTH. Fourteen normal men eating a normal sodium diet were studied. In eight, PRA, plasma aldosterone (PAC), plasma cortisol (F), and serum K concentrations were determined after 4 h of upright posture and infusion of vehicle (D5W) or DA at 0.1, 0.4, and 2.0 micrograms/kg X min. Six other normal men were kept supine for 3 h and, on separate days, upright for 3 h and given iv M (10-mg bolus dose), AII (1 and 4 pmol/kg X min for 30 min), and ACTH (20 and 120 mU/h for 30 min). PAC, PRA, F, and K were measured before and after these three secretogogues were administered. In the presence of vehicle, mean PAC increased by 15.1 +/- 4.3 (+/- SEM) ng/dL after 4 h of upright posture. In the presence of DA infused at 0.1, 0.4, and 2.0 micrograms/kg X min, the PAC response to upright posture was decreased to 9.7 +/- 2.5 (P = NS), 7.5 +/- 3.9 (P less than 0.05), and 8.1 +/- 2.0 (P less than 0.05) ng/dL, respectively. This occurred without a decrease in PRA, F, or K. The stimulation of PAC 10 and 20 min after a 10-mg bolus dose of M was 9.6 +/- 3.3 and 9.3 +/- 2.6 ng/dL, respectively, in supine subjects and 8.3 +/- 2.3 and 10.8 +/- 3.4 ng/dL 10 and 20 min after the M dose in upright subjects. The responses of PAC to ACTH and AII also were unchanged after 3 h of upright posture. We conclude that upright posture sensitizes the adrenal cortex to inhibition of aldosterone secretion by DA without affecting other modifiers of aldosterone secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Aldosterona/sangue , Dopamina/farmacologia , Postura , Hormônio Adrenocorticotrópico/farmacologia , Adulto , Angiotensina II/farmacologia , Humanos , Masculino , Metoclopramida/farmacologiaRESUMO
Aldosterone secretion in man is stimulated by potassium, ACTH, and angiotensin II and is inhibited by dopamine (DA). In normal sodium-replete supine individuals, aldosterone secretion is under maximum tonic inhibition by DA. Dopaminergic control of aldosterone secretion is modified by dietary sodium depletion. To determine the physiological significance of dopaminergic inhibition of aldosterone secretion, we studied the effect of DA on the aldosterone response to upright posture. Twelve normal men were studied while eating an ad libitum sodium diet, and the effect of DA was determined in the supine and upright positions. Plasma aldosterone (PAC), plasma cortisol (F), plasma aldosterone-stimulating factor (ASF), PRA, and blood pressure were measured while the men were supine and after 4 h of upright posture during an infusion of 5% dextrose vehicle and during a DA infusion of 4.0 micrograms/kg X min. The men also were studied as a time control in the supine position while receiving vehicle or DA. PAC increased from a mean basal value of 20.4 +/- 3.2 ng/dl (+/- SE) by 25.9 +/- 5.1 ng/dl to a peak of 44.4 +/- 2.4 ng/dl in response to upright posture during vehicle infusion. The PAC response to upright posture was reduced to 7.4 +/- 1.8 ng/dl (P less than 0.05) when DA was infused. The increase in PRA with upright posture was 3.7 +/- 1.3 ng/ml X h during the vehicle infusion and 4.1 +/- 1.1 ng/ml X h (P = NS) during the DA infusion. ASF, F, and blood pressure were not altered by upright posture and DA. PAC did not change in the six men infused with DA while supine. Therefore, DA inhibits upright aldosterone responses without affecting PRA, ASF, or F.
Assuntos
Aldosterona/metabolismo , Dopamina/fisiologia , Postura , Adulto , Aldosterona/sangue , Pressão Sanguínea/efeitos dos fármacos , Dopamina/farmacologia , Glicoproteínas , Humanos , Hidrocortisona/sangue , Infusões Parenterais , Masculino , Proteínas/metabolismo , Renina/sangueRESUMO
The McCune-Albright syndrome (MAS) is characterized clinically by polyostotic fibrous dysplasia, café-au-lait skin lesions, sexual precocity, and various other endocrinopathies. Recent investigations suggest an etiological role for embryonic somatic missense mutations that predict the substitution of a His or Cys for Arg at amino acid 201 of the Gs alpha-subunit (Gs alpha). Identification of these mutations in affected tissues is a sensitive assay that may help define a more complete clinical spectrum of the MAS. We investigated a woman who developed fibrous dysplasia 24 yr after premature menstruation. To determine if this was an unusual MAS variant, DNA and RNA were analyzed from affected and unaffected tissues. From samples of affected rib and normal rib DNA was extracted, amplified by polymerase chain reaction, subcloned, and sequenced. RNA was extracted from affected bone, reverse transcribed, amplified by polymerase chain reaction, subcloned, and sequenced. DNA sequence predicting a His for Arg substitution at Gs alpha amino acid 201 was found in 47% of the recombinant plasmids from DNA of affected bone and 17% of the plasmids from DNA of unaffected bone; a significant (P < 0.05) difference in frequency. The His201 substitution was found in 42% of the recombinant plasmids from RNA of affected bone. We conclude that this clinical variant is qualitatively indistinguishable from presentations of the complete MAS.
Assuntos
Displasia Fibrosa Poliostótica/genética , Proteínas de Ligação ao GTP/genética , Mutação , Costelas/metabolismo , Adulto , Sequência de Bases , DNA/genética , Enzimas de Restrição do DNA/análise , Feminino , Displasia Fibrosa Poliostótica/patologia , Humanos , Sondas Moleculares/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Costelas/patologiaRESUMO
Generalized glucocorticoid resistance presents with clinical features secondary to excess production of mineralocorticoids and adrenal androgens. It is our hypothesis that these clinical and biochemical features will respond to glucocorticoid therapy. We tested this hypothesis in a boy with generalized glucocorticoid resistance and increased adrenal androgens. Dexamethasone was administered from age 7 6/12 yr until the onset of true puberty at 11 0/12 yr. Serum concentrations of cortisol and adrenal androgens decreased to the normal or near normal range. The accelerated precocity improved. Secondary sex characteristics did not progress; the difference between bone age and chronological age decreased from 3 1/2 yr to 2 yr, and the difference between height age and bone age decreased from 2 yr to 1/2 yr. We conclude that dexamethasone is effective and safe therapy for the sexual precocity of generalized glucocorticoid resistance.
Assuntos
Dexametasona/uso terapêutico , Resistência a Medicamentos , Glucocorticoides , Puberdade Precoce/tratamento farmacológico , Determinação da Idade pelo Esqueleto , Androgênios/sangue , Estatura , Criança , Dexametasona/administração & dosagem , Humanos , Hidrocortisona/sangue , Masculino , Puberdade Precoce/etiologia , Puberdade Precoce/fisiopatologiaRESUMO
Inappropriate ACTH secretion with bilateral diffuse or macronodular adrenal hyperplasia is the most common cause of Cushing's syndrome. This report describes a patient with Cushing's syndrome and feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia. A 47-yr-old black man presented with Cushingoid features, diabetes mellitus, hypertension, impotence, and gynecomastia. Urinary cortisol and 17-hydroxycorticosteroid excretion were 94 nmol/mmol creatinine (normal, less than 32) and 5.8 mumol/mmol creatinine (normal, 0.6-3.6), respectively. Both decreased by less than 30% after administration of dexamethasone (8 and 16 mg/day), and urinary 17-hydroxycorticosteroid excretion did not increase after metyrapone (750 mg, orally, every 4 h for six doses). Plasma ACTH was undetectable (less than 1 pmol/L) and was not stimulated by administration of metyrapone or ovine CRH. Serum testosterone was 5.2 nmol/L (normal, 7-30), FSH was 5 U/L (normal, 3-18), LH was 2.8 U/L (normal, 1.5-9.2), and estrone was 767 pmol/L (normal, 55-240). Both adrenal glands were enlarged, with a total weight of 86 g (normal, 8-10), and contained multiple nodules (diameter, greater than 0.5 cm) composed of two active cell types, one of which was also observed between the nodules. Cushing's syndrome with feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia is an unusual process of unknown etiology that should be included with the other known causes of Cushing's syndrome.
Assuntos
Hiperplasia Suprarrenal Congênita/complicações , Hormônio Adrenocorticotrópico , Síndrome de Cushing/etiologia , Glândulas Suprarrenais/patologia , Hiperplasia Suprarrenal Congênita/metabolismo , Hiperplasia Suprarrenal Congênita/patologia , Adrenalectomia , Hormônio Adrenocorticotrópico/metabolismo , Dexametasona , Estrona/metabolismo , Feminização/etiologia , Humanos , Hidrocortisona/metabolismo , Masculino , Metirapona , Pessoa de Meia-Idade , Testosterona/metabolismoRESUMO
Primary cortisol resistance (PCR) is a rare cause of hypercortisolism and usually does not produce clinical manifestations. This report describes primary cortisol resistance in a boy with isosexual precocity. A 6 7/12-yr-old boy had Tanner stage 3 pubic hair, accelerated linear growth, and advanced bone age (10 yr), but normal (for age) tests. There were no features of glucocorticoid excess. Serum androstenedione and dehydroepiandrosterone concentrations were 4.7 +/- 0.3 nmol/L (mean +/- SEM of four measurements; normal less than 1.2) and 13.5 nmol/L (single measurement; normal, 1.0-2.2), respectively. The serum testosterone concentration was 0.9 nmol/L (normal, less than 0.7), and FSH and LH were normal. Serum cortisol concentrations were 1590 +/- 110 nmol/L (normal, 190-630) and 580 +/- 60 nmol/L (normal, 50-410) at 0800 and 2000 h, respectively. Serum cortisol responded normally to insulin-induced hypoglycemia. Glucocorticoids and adrenal androgens were resistant to suppression by dexamethasone. The Kd of [3H]dexamethasone binding to the glucocorticoid receptors of mononuclear leukocytes was increased (6.4 +/- 0.8 nM; mean +/- SEM of four determinations; normal, 1.4-3.4; P less than 0.001), but the binding capacity was normal. This patient with isosexual precocity has PCR, as indicated by functionally abnormal glucocorticoid receptors and hypercortisolism without other clinical or biochemical manifestations of Cushing's syndrome. Excessive adrenal stimulation by ACTH caused increased secretion of both cortisol and adrenal androgens, and the latter caused the clinical manifestations. PCR should be considered in other male children with isosexual precocity or female children with heterosexual precocity.
Assuntos
Glândulas Suprarrenais/fisiopatologia , Hidrocortisona/sangue , Puberdade Precoce/sangue , Androgênios/biossíntese , Androgênios/sangue , Criança , Dexametasona , Resistência a Medicamentos/fisiologia , Hormônio Foliculoestimulante/sangue , Glucocorticoides/sangue , Humanos , Hidrocortisona/fisiologia , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Insulina/administração & dosagem , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/etiologia , Puberdade Precoce/fisiopatologia , Receptores de Glucocorticoides/sangue , Receptores de Glucocorticoides/fisiologia , Testosterona/sangueRESUMO
Papillary thyroid carcinoma usually is sporadic, but may occur in a familial form. The complete clinical and pathological phenotype of familial papillary thyroid carcinoma (fPTC) has not been determined, and the susceptibility gene(s) is unknown. We investigated the clinical and pathological characteristics of an unusually large three-generation fPTC kindred to characterize more fully the clinical phenotype. We performed linkage analysis to determine the chromosomal location of a fPTC susceptibility gene. In addition to the known association of fPTC with nodular thyroid disease, we observed the otherwise rare entity of papillary renal neoplasia (PRN) in two kindred members, one affected with PTC and the other an obligate carrier. The multifocality of PRN in one subject adds weight to the likelihood of a true genetic predisposition to PRN. Both genetic linkage and sequence analysis excluded MET, the protooncogene of isolated familial PRN, as the cause of the fPTC/PRN phenotype. A genome-wide screening and an investigation of specific candidate genes demonstrated that the fPTC/PRN phenotype was linked to 1q21. A maximum three-point log of likelihood ratio score of 3.58 was observed for markers D1S2343 and D1S2345 and for markers D1S2343 and D1S305. Critical recombination events limited the region of linkage to approximately 20 cM. A distinct inherited tumor syndrome has been characterized as the familial association of papillary thyroid cancer, nodular thyroid disease, and papillary renal neoplasia. The predisposing gene in a large kindred with this syndrome has been mapped to 1q21.
Assuntos
Carcinoma Papilar/genética , Mapeamento Cromossômico , Neoplasias Renais/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Carcinoma Papilar/patologia , Cromossomos Humanos Par 7 , Feminino , Marcadores Genéticos , Humanos , Neoplasias Renais/patologia , Funções Verossimilhança , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem , Proteínas Proto-Oncogênicas c-met/genética , Proto-Oncogenes , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologiaRESUMO
Diabetic hyperosmolar coma is a syndrome of marked hyperglycemia and minimal ketoacidosis. In general, the serum glucose concentrations are not predictive of the serum ketoacid concentrations in acutely decompensated diabetes. The endocrine factors that modulate glucose concentrations may be different from those that modulate ketoacid concentrations in patients with acutely decompensated diabetes. To test this hypothesis, regression analysis was used to determine the endocrine and metabolic characteristics that correlated with serum concentrations of glucose and ketoacids in 26 diabetic patients with spontaneous, acute hyperglycemia. All patients had a serum glucose level greater than 390 mg/dl, and ketoacid levels were from 0.17 to 25.5 mM. Multiple regression analysis showed that increased serum glucose concentrations correlated with increased plasma glucagon levels (p = 0.0007, r2 = 0.45), but with no other factors. Increased total ketoacid levels (acetoacetate plus 3-hydroxybutyrate) correlated with increased free fatty acid levels (p = 0.0001), decreased C-peptide levels (p = 0.002), and increased body mass index (p = 0.002) (r2 = 0.72). Body mass index only correlated with ketoacid levels, when it was analyzed with C-peptide and free fatty acid levels. A model is proposed that predicts the serum glucose and ketoacid concentrations in patients with acutely decompensated diabetes. Glucagon modulates the serum glucose concentration in these patients with an absolute or relative insulin deficiency. Total serum ketoacid levels are determined by the serum free fatty acid concentration, residual pancreatic insulin secretion (as reflected by C-peptide), and the patient's body habitus. This model allows for the marked hyperglycemia and minimal ketosis of diabetic nonketotic hyperosmolar coma, as well as the glucose and ketoacid concentrations in other presentations of acutely decompensated diabetes.
Assuntos
Glicemia/análise , Diabetes Mellitus/sangue , Coma Diabético/sangue , Cetoacidose Diabética/sangue , Hiperglicemia/sangue , Coma Hiperglicêmico Hiperosmolar não Cetótico/sangue , Cetoácidos/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Peptídeo C/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Hormônio do Crescimento/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Análise de RegressãoRESUMO
Cushing's syndrome due to bronchial carcinoid tumors that secrete adrenocorticotropin (ACTH) may be difficult to distinguish from pituitary Cushing's disease, since the responses to dexamethasone and metyrapone are sometimes similar. Recently, the ACTH and cortisol responses to ovine corticotropin-releasing factor (oCRF) have been shown to be different in pituitary Cushing's disease than in Cushing's syndrome due to other causes. It is not known if the response to oCRF can distinguish pituitary Cushing's disease from those ACTH-secreting bronchial carcinoid tumors that respond to dexamethasone and metyrapone. A case of Cushing's syndrome due to an ACTH-secreting bronchial carcinoid is described in which the responses to dexamethasone, metyrapone, and oCRF were indistinguishable from the responses observed in pituitary Cushing's disease. A bronchial carcinoid tumor should be considered even when responses to dexamethasone, metyrapone, and oCRF suggest pituitary Cushing's disease.
Assuntos
Síndrome de ACTH Ectópico/etiologia , Neoplasias Brônquicas/metabolismo , Tumor Carcinoide/metabolismo , Hormônio Liberador da Corticotropina , Dexametasona , Metirapona , Síndromes Endócrinas Paraneoplásicas/etiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Síndrome de Cushing/etiologia , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Hidroxiesteroides/sangueRESUMO
PURPOSE: To assess the feasibility of somatostatin receptor scintigraphy for patients with Cushing's syndrome caused by tumors secreting ectopic corticotropin or corticotropin-releasing hormone (CRH). PATIENTS AND METHODS: Ten patients with Cushing's syndrome, nine with ectopic corticotropin-secreting tumors and one with a CRH-secreting tumor, were consecutively studied. For comparison purposes, eight patients with corticotropin-secreting pituitary tumors and one patient with an autonomous adrenal adenoma were investigated. In vivo tumor localization was performed for all patients using a radionuclide-coupled somatostatin analog. The results obtained with this technique were compared with those obtained with conventional imaging techniques. For some patients, the clinical effects of octreotide therapy were evaluated. RESULTS: Somatostatin analog scintigraphy successfully identified the primary ectopic corticotropin-secreting and CRH-secreting tumors or their metastases, or both, in 8 of 10 patients; in 2 patients with corticotropin-secreting bronchial carcinoids, the tumors could not be visualized. Normal scans were obtained for the 8 patients with corticotropin-secreting pituitary tumors and the one patient with an adrenal adenoma. CONCLUSION: Somatostatin analog scintigraphy can be included as a diagnostic step in the workup of Cushing's syndrome patients with a suspected ectopic corticotropin-secreting tumor or a CRH-secreting tumor.
Assuntos
Síndrome de ACTH Ectópico/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Síndrome de Cushing/metabolismo , Neoplasias/metabolismo , Receptores de Somatostatina/metabolismo , Síndrome de ACTH Ectópico/complicações , Síndrome de ACTH Ectópico/tratamento farmacológico , Adulto , Idoso , Autorradiografia , Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/etiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Neoplasias Hipofisárias/metabolismo , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
A young woman with an occult bronchogenic carcinoma presented with secondary amenorrhea and an elevated beta subunit of human chorionic gonadotropin that was mistakenly attributed to pregnancy. Physicians should be aware that this carcinoma may present solely with an elevated beta human chorionic gonadotropin value, and the potential exists for confusion with a pregnancy state in women of childbearing age.
Assuntos
Carcinoma Broncogênico/diagnóstico , Gonadotropina Coriônica/metabolismo , Hormônios Ectópicos/metabolismo , Neoplasias Pulmonares/diagnóstico , Fragmentos de Peptídeos/metabolismo , Gravidez , Adulto , Carcinoma Broncogênico/metabolismo , Gonadotropina Coriônica Humana Subunidade beta , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Testes de GravidezRESUMO
Somatostatin-receptor imaging is an effective method for localizing and staging neuroendocrine tumors. We describe patients with gastroenteropancreatic endocrine tumors who underwent preoperative indium In 111 pentetreotide scintigraphy. In 3 patients without prior resections, the results of a 111In pentetreotide scan were positive because of unsuspected regional lymph node metastases without localization of the primary tumors. In these patients, an extensive intraoperative search was required to identify the primary tumors, despite the positive preoperative scan results. In a fourth patient, who had previously undergone resection of a duodenal gastrinoma, 2 regional nodal metastases were identified by a 111In pentetreotide scan.
Assuntos
Radioisótopos de Índio , Tumores Neuroendócrinos/diagnóstico por imagem , Receptores de Somatostatina/análise , Somatostatina/análogos & derivados , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/secundário , CintilografiaRESUMO
Familial papillary thyroid carcinoma (fPTC) is an inherited tumor syndrome characterized by isolated papillary thyroid carcinoma (PTC) in affected subjects. Its etiology is unknown. Large multigeneration families with PTC are very rare, and therefore, modern genetic linkage studies have not been applied extensively to this disorder. Familial adenomatous polyposis coli (FAP) is an inherited tumor syndrome enriched in PTC. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene that is located in the 5q21 region. It is not known if fPTC is a phenotypic variant of FAP, or if it is a genetically distinct disorder. We report a large 3-generation fPTC kindred and use linkage analysis to test the hypothesis that fPTC and FAP are genetically distinct. In this kindred there are 25 living informative subjects; 5 have PTC, and 1 is an obligate carrier. Inheritance is autosomal dominant with incomplete penetrance. There is vertical transmission, multifocal disease, an average age of onset of 36 years, and 1 subject has colon cancer. The probability is approximately 1 in 2 billion against the clustering of 5 sporadic PTC cases in this kindred. To test for linkage to the APC gene we used 2 highly polymorphic markers, D5S656 and D5S421, which are located within a maximum distance of 1.7 megabase (Mb) of the APC gene and within an estimated genetic region of less than 1 centimorgan (cM) from each other. After polymerase chain reaction (PCR) amplification 18 family members were genotyped. Construction and inspection of haplotypes showed that the affected subjects do not share the same allelic composition. Using a penetrance ratio of 75%, linkage was excluded at 2 cM and 3 cM on both sides of D5S656 and D5S421, respectively. The combined haplotype of these 2 markers provided an exclusion region of 4 cM. We conclude that fPTC is genetically distinct from FAP.
Assuntos
Polipose Adenomatosa do Colo/genética , Carcinoma Papilar/genética , Genes APC , Neoplasias da Glândula Tireoide/genética , Adulto , Feminino , Ligação Genética , Marcadores Genéticos , Haplótipos/genética , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
The diagnosis of diabetes mellitus is established by history, physical examination, and measurements of serum or plasma glucose concentrations under specific conditions. This disorder represents the final common expression of diverse etiologies which are incompletely understood. The treatable causes of diabetes should be identified, and the appropriate therapy initiated. Distinguishing Type I and Type II diabetes is often useful, but not a necessary prerequisite for initiating therapy. As we begin to understand the underlying causes of diabetes, our emphasis is likely to shift from a diagnosis based on metabolic characteristics to a diagnosis based on etiology.
Assuntos
Diabetes Mellitus/diagnóstico , Glicemia/análise , Diabetes Mellitus/classificação , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Gravidez , Gravidez em DiabéticasRESUMO
This prospective study investigates the relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) in patients with thyroid nodules (TNs). We prospectively examined 2100 patients with 2753 TNs between January 5, 2010 and August 15, 2013. A total of 2023 patients with 2669 TNs met the inclusion criteria of TN ≥5âmm and age ≥18 years. Each patient had blood drawn before fine-needle aspiration biopsy (FNAB) for the following measurements: TSH, free thyroxine, free tri-iodothyronine, thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb). Diagnosis of TC was based on pathology analysis of thyroidectomy tissue. The associations of TC with the independent variables were determined by univariate and multivariate logistic regression analysis and reported as adjusted odds ratio (OR) with 95% CI. A total of 248 malignant nodules were found in 233 patients. There was an association of TC with both increased serum TgAb concentration and age<45 years. An elevated serum TgAb concentration was found in 10.2% of patients (182 of 1790) with benign nodules as compared with 20.6% of patients (48 of 233) with malignant nodules (P≤0.0001). TgAb (OR=2.24: CI=1.57, 3.19) and TSH ≥1âµIU/ml (OR (95% CI)) OR: 1.49 (1.09, 2.03) were significant predictors of TC in multivariate analysis controlling for age and gender. TC was not associated with serum concentrations of TPOAb. In patients with TN, elevated serum concentration of TgAb and TSH ≥1âµIU/ml are independent predictors for TC. The association between HT and TC is antibody specific.