RESUMEN
Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.
Asunto(s)
Carcinoma Papilar/sangre , Tiroglobulina/sangre , Neoplasias de la Tiroides/sangre , Carcinoma Papilar/terapia , Humanos , Radioisótopos de Yodo/uso terapéutico , Metástasis de la Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Proteínas Recombinantes/administración & dosificación , Factores de Riesgo , Sensibilidad y Especificidad , Neoplasias de la Tiroides/terapia , Tiroidectomía , Tirotropina/administración & dosificaciónRESUMEN
Pituitary tumors are frequently encountered intracranial neoplasms. They present with a variety of clinical manifestations that include symptoms and signs of excessive hormone secretion by the tumor, signs of hormone deficits by the normal pituitary gland and others related to expansion of the tumor mass and the resulting compression of surrounding structures such as the optic chiasm and cranial nerves. Advances in molecular biology, immunocytochemical staining and imaging, and the introduction of new treatment options have improved our understanding of the natural history of these adenomas and their management. Available treatments include surgical, medical and radiation therapy. Although the primary treatment for each tumor type may vary, it is important to consider all available options and select the most applicable for that patient. The interaction of all members of management team, including the primary care provider, the endocrinologist and the neurosurgeon in selecting the treatment course can only improve therapeutic outcome. Regardless of the initial choice of treatment,follow-up of all patients should be maintained indefinitely. The managing physician should be familiar with the natural history and long-term complications of pituitary adenomas, and with the side effects of treatments given over the years.
Asunto(s)
Neoplasias Hipofisarias , Acromegalia/etiología , Adenoma/clasificación , Adenoma/diagnóstico , Adenoma/tratamiento farmacológico , Adenoma/epidemiología , Adenoma/fisiopatología , Adenoma/cirugía , Hormona Adrenocorticotrópica/metabolismo , Adulto , Manejo de Caso , Niño , Células Clonales/patología , Terapia Combinada , Diabetes Insípida Neurogénica/tratamiento farmacológico , Diabetes Insípida Neurogénica/etiología , Agonistas de Dopamina/uso terapéutico , Reacciones Falso Negativas , Femenino , Hormona de Crecimiento Humana/metabolismo , Humanos , Hidrocortisona/metabolismo , Hipofisectomía/efectos adversos , Hipofisectomía/métodos , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/etiología , Sistema Hipotálamo-Hipofisario/fisiopatología , Incidencia , Masculino , Persona de Mediana Edad , Síndrome de Nelson/etiología , Octreótido/uso terapéutico , Pruebas de Función Hipofisaria , Hormonas Hipofisarias/análisis , Hormonas Hipofisarias/metabolismo , Hormonas Hipofisarias/uso terapéutico , Neoplasias Hipofisarias/clasificación , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/terapia , Sistema Hipófiso-Suprarrenal/metabolismo , Embarazo , Complicaciones Neoplásicas del Embarazo/terapia , Prevalencia , Prolactina/sangre , Prolactina/metabolismo , Prolactinoma/sangre , Prolactinoma/complicaciones , Prolactinoma/diagnósticoRESUMEN
BACKGROUND: Women with hypothyroidism that is being treated with thyroxine often need higher doses when they are pregnant. Whether this need can be attributed solely to estrogen-induced increases in serum thyroxine-binding globulin or whether other factors are involved is not known. METHODS: In 11 postmenopausal women with normal thyroid function and 25 postmenopausal women with hypothyroidism treated with thyroxine, I assessed thyroid function before they started estrogen therapy and every 6 weeks for 48 weeks thereafter. The women with hypothyroidism included 18 women receiving thyroxine-replacement therapy and 7 women receiving thyrotropin-suppressive thyroxine therapy. On each occasion, serum thyroxine, free thyroxine, thyrotropin, and thyroxine-binding globulin were measured. RESULTS: In the women with normal thyroid function, the serum free thyroxine and thyrotropin concentrations did not change, whereas at 12 weeks the mean (+/-SD) serum thyroxine concentration had increased from 8.0+/-0.9 microg per deciliter (103+/-12 nmol per liter) to 10.4+/-1.5 microg per deciliter (134+/-19 nmol per liter, P<0.001) and the serum thyroxine-binding globulin concentration had increased from 20.3+/-3.5 mg per liter to 31.3+/-3.2 mg per liter, P<0.001). The women with hypothyroidism had similar increases in serum thyroxine and thyroxine-binding globulin concentrations during estrogen therapy, but their serum free thyroxine concentration decreased from 1.7+/-0.4 ng per deciliter (22+/-5 pmol per liter) to 1.4+/-0.3 ng per deciliter (18+/-4 pmol per liter, P<0.001) and their serum thyrotropin concentration increased from 0.9+/-1.1 to 3.2+/-3.1 microU per milliliter (P<0.001). The serum thyrotropin concentrations increased to more than 7 microU per milliliter in 7 of the 18 women in the thyroxine-replacement group and to more than 1 microU per milliliter in 3 of the 7 women in the thyrotropin-suppression group. CONCLUSIONS: In women with hypothyroidism treated with thyroxine, estrogen therapy may increase the need for thyroxine.
Asunto(s)
Estrógenos Conjugados (USP)/uso terapéutico , Hipotiroidismo/tratamiento farmacológico , Proteínas de Unión a Tiroxina/metabolismo , Tiroxina/administración & dosificación , Adulto , Estrógenos Conjugados (USP)/farmacología , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/sangre , Medroxiprogesterona/uso terapéutico , Persona de Mediana Edad , Posmenopausia/sangre , Valores de Referencia , Pruebas de Función de la Tiroides , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiología , Neoplasias de la Tiroides/tratamiento farmacológico , Tirotropina/sangre , Tiroxina/sangre , Tiroxina/uso terapéuticoRESUMEN
Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this setting are largely due to compression of pituitary stalk and portal vessels. Headaches (HAs) are frequently seen in patients with large adenomas and at times in those with microadenomas. Because the walls of the sella turcica are relatively rigid, we postulate that tumor growth within the sella increases intrasellar pressure (ISP), which in turn impairs portal blood flow, resulting in mild hyperprolactinemia and hypopituitarism. We also postulate that increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pituitary adenomas. MISP was measured using a commonly available intracranial monitoring kit where a fiberoptic transducer was inserted through a 2-mm dural incision at the time of adenomectomy. Patients with deficient FSH, LH, ACTH, or TSH secretion were considered hypopituitary. Data on serum PRL levels were included for analysis only in patients whose adenomas had negative immunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 13.5 and a median of 26 mm Hg. The pressure measurements were higher in patients with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involved in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pituitary function, suggest that increased ISP is a major mechanism involved in the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contributing to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased ISP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.
Asunto(s)
Adenoma/complicaciones , Cefalea/etiología , Hiperprolactinemia/etiología , Hipopituitarismo/etiología , Hipertensión Intracraneal/complicaciones , Neoplasias Hipofisarias/complicaciones , Adenoma/patología , Adenoma/cirugía , Femenino , Humanos , Presión Intracraneal , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Prolactina/sangreRESUMEN
STUDY OBJECTIVE: To assess the value of plasma glucose concentration alone as a predictor of neurologic dysfunction in nondiabetic subjects with normal baseline neurologic examination and electroencephalographic (EEG) findings. METHODS: Neurologic function and EEG results were evaluated in 17 subjects before and during insulin-induced hypoglycemia using relevant and reliable clinical tools for bedside use. RESULTS: Hypoglycemia (mean nadir concentration, 30 mg/dL) was without effect on level of consciousness or cranial nerve, motor, sensory, vestibulocerebellar, language, or simple visuospatial functions. Attention was minimally impaired in all subjects, but memory in only 3. EEG results remained normal in 5 subjects; minimal to moderate nonspecific changes occurred in the rest. All patients manifested signs of sympathetic stimulation from hypoglycemia, including tremor, tachycardia, and diaphoresis. The manifestations of neuroglycopenia did not correlate significantly with nadir plasma glucose or duration of hypoglycemia. CONCLUSION: Moderately severe hypoglycemia of short duration can be neurologically occult, or subtle inattention can be its first and only clinical manifestation. Our findings are at variance with reports in the emergency medicine literature in which marked deficits are universally present at glucose concentrations equal to those attained in this study. This discrepancy suggests that the expression of neuroglycopenia is multifactorially determined and that plasma glucose concentration alone does not predict neurologic dysfunction in nondiabetic subjects with normal baseline neurologic examinations.
Asunto(s)
Glucemia , Hipoglucemia/complicaciones , Enfermedades del Sistema Nervioso/etiología , Adulto , Anciano , Cognición , Electroencefalografía , Femenino , Humanos , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Hipoglucemia/fisiopatología , Insulina , Masculino , Memoria , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/clasificación , Examen Neurológico , Valor Predictivo de las PruebasRESUMEN
Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. We postulated that hypopituitarism in this setting, is primarily caused by compression of the portal vessels and/or pituitary stalk. If this were the case, the dynamics of PRL secretion in this instance would be similar to those in patients with stalk section, dopamine deficiency, or hypothalamic disease. Furthermore, as hypopituitarism in this setting is largely reversible, we postulate that PRL dynamics should also normalize after adenomectomy as a result of the resumption of hypothalamic regulation of pituitary hormone secretion. To test these hypotheses, we examined PRL responsiveness to TRH and the dopamine antagonist, perphenazine (PZ), in patients with pituitary macroadenomas who had hypopituitarism and others with intact pituitary function (controls). Dynamic studies were performed before and 2-3 months after total or subtotal adenomectomy, and the results were correlated with alterations in other pituitary function. In addition, plasma ACTH, cortisol, and PRL levels were measured hours to days after surgery to investigate immediate alterations in pituitary function following surgical decompression. Before surgery, hypopituitary patients had higher serum PRL level than controls (25.5 +/- 12 vs. 11 +/- 3 micrograms/L; P < 0.001). Preoperative dynamic testing of PRL secretion in hypopituitary patients demonstrated an increase in PRL levels after TRH, but not after PZ, administration. In contrast, PRL levels increased appropriately when either stimulus was given to controls. Hours after adenomectomy, PRL levels decreased by 50% in hypopituitary patients (P < 0.0001) and remained so until discharge. In contrast, controls had a transient increase in serum PRL levels after adenomectomy. After surgery, 25 of 43 previously hypopituitary patients recovered part or all pituitary function. Serum PRL levels in the latter subgroup became normal and increased appropriately after stimulation with either TRH or PZ. In contrast, patients who did not recover pituitary function had lower PRL levels that increased minimally after TRH or PZ. The mild increase in serum PRL levels in hypopituitary patients and the discordant responses to stimulation with TRH and PZ suggest dopamine deficiency as a cause of hyperprolactinemia. The drop in serum PRL levels immediately after surgery, at a time when other pituitary hormones (e.g. ACTH), were documented to rise suggests restoration of hypothalamic control over pituitary hormone secretion. The pattern of PRL responses to stimulation in patients recovering function postoperatively was similar to that in controls, although the incremental rise was subnormal.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Adenoma/metabolismo , Hipopituitarismo/metabolismo , Neoplasias Hipofisarias/metabolismo , Prolactina/metabolismo , Adenoma/fisiopatología , Adenoma/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotiazinas/farmacología , Hipófisis/fisiopatología , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/cirugía , Periodo Posoperatorio , Prolactina/sangre , Hormona Liberadora de Tirotropina/farmacología , Factores de TiempoRESUMEN
Mild hyperprolactinemia frequently accompanies the hypopituitarism associated with pituitary macroadenomas not secreting PRL. Because of this association, hypopituitarism was postulated to be due to compression of portal vessels. We postulate that resumption of hypothalamic control over pituitary function occurs immediately after adenomectomy. To test this hypothesis, we examined pituitary function before and after transsphenoidal adenomectomy in 26 ACTH-deficient patients and 23 subjects with normal adrenal and thyroidal functions (control group). Glucocorticoids, given only to ACTH-deficient subjects, were withdrawn 36 h after surgery. ACTH, cortisol, and PRL levels were measured twice daily in all patients. Both ACTH and PRL levels increased hours after surgery in controls and returned to baseline over 4 days. In all hypopituitary subjects, PRL levels decreased by 50% within hours of adenomectomy and remained so until discharge. ACTH levels, measured simultaneously, increased within hours in 17 of 26 hypopituitary patients, all of whom recovered normal adrenal function before discharge. Nine additional patients had low ACTH levels and required cortisol replacement. The reciprocal changes in PRL and ACTH levels measured simultaneously, hours after surgery, support the hypothesis that hypopituitarism is reversible and largely caused by compression of the protal vessels and the resulting interruption of delivery of hypothalamic hormones. The persistence of hypopituitarism in some patients suggests that ischemic necrosis of the anterior pituitary could limit recovery.
Asunto(s)
Adenoma/cirugía , Hipófisis/fisiopatología , Neoplasias Hipofisarias/cirugía , Adenoma/fisiopatología , Glándulas Suprarrenales/fisiopatología , Hormona Adrenocorticotrópica/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hidrocortisona/sangre , Cinética , Hormona Luteinizante/sangre , Masculino , Ovario/fisiopatología , Neoplasias Hipofisarias/fisiopatología , Prolactina/sangre , Testículo/fisiopatología , Testosterona/sangre , Glándula Tiroides/fisiopatologíaRESUMEN
OBJECTIVE: To determine the effects of androgen administration on measures of thyroid function and thyroid hormone replacement doses in women with breast cancer. DESIGN: Consecutive patients with metastatic, hormone-dependent breast cancer who were eligible for androgen treatment. INTERVENTIONS: Androgen therapy (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was effective in controlling tumor growth. PATIENTS: 7 patients with no known thyroid disease and 4 others receiving long-term treatment for hypothyroidism. MEASUREMENTS: Serum levels of total and free thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin were determined before and every 4 weeks after androgen therapy was initiated. RESULTS: Within 4 weeks of androgen administration to the seven patients without thyroid disease, serum levels of total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated free thyroxine index and measured free hormone levels remained unchanged. Six to 12 weeks after androgen therapy was discontinued, all seven patients remained clinically euthyroid, and serum levels returned to baseline values. In contrast, clinical hyperthyroidism developed shortly after androgen was administered to four patients who received long-term thyroid hormone replacement therapy. Within 4 weeks of treatment, the serum free T4 level increased in each of the four patients, whereas the TSH level decreased. Thyroid hormone doses had to be reduced by 25% to 50% to maintain euthyroidism. CONCLUSIONS: The study documents the reversible effects of androgens on thyroid hormone levels and indicates the need to reduce thyroid replacement doses in women during androgen therapy. Monitoring thyroid hormone levels in patients receiving replacement therapy and perhaps in those with autonomous thyroid function is necessary after androgen therapy.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Fluoximesterona/farmacología , Hipotiroidismo/tratamiento farmacológico , Tiroxina/administración & dosificación , Anciano , Neoplasias de la Mama/sangre , Neoplasias de la Mama/complicaciones , Femenino , Fluoximesterona/uso terapéutico , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/complicaciones , Persona de Mediana Edad , Cuidados Paliativos , Tirotropina/efectos de los fármacos , Tiroxina/sangre , Tiroxina/efectos de los fármacos , Tiroxina/uso terapéutico , Proteínas de Unión a Tiroxina/efectos de los fármacosRESUMEN
We present an unusual case of Langerhans cell histiocytosis (LCH) involving the thyroid gland initially diagnosed by fine needle aspiration biopsy in a 16-year-old boy. The cytologic findings in LCH involving the thyroid include high cellularity, isolated Langerhans cells with prominent nuclear grooves, multinucleate Langerhans cells, eosinophils, lymphocytes and rare benign follicular cells. Confirmation of LCH was obtained by core biopsy, positive S-100 protein immunohistochemical staining and the demonstration of Birbeck granules on electron microscopy. We present the complete clinicopathologic features of this case with a review of the literature and discussion of the differential diagnosis.
Asunto(s)
Histiocitosis de Células de Langerhans/patología , Enfermedades de la Tiroides/patología , Adolescente , Biopsia con Aguja , Diagnóstico Diferencial , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/metabolismo , Humanos , Masculino , Microscopía Electrónica , Proteínas S100/análisis , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/metabolismoRESUMEN
This report describes two cases of Cushing's syndrome associated with radiologic abnormalities in the lung and brain. In both cases, the pathologic diagnosis of the intracranial lesion was unsuspected and prompted changes in management. These cases illustrate that the etiology of pulmonary and central nervous system mass lesions in patients with Cushing's syndrome may not be predicted on clinical grounds or by conventional radiologic methods. A tissue diagnosis is essential as a guide to appropriate management, and biopsies of such lesions are indicated.
Asunto(s)
Absceso Encefálico/diagnóstico , Neoplasias Encefálicas/diagnóstico , Tumor Carcinoide/diagnóstico , Síndrome de Cushing/diagnóstico , Neoplasias Pulmonares/diagnóstico , Nocardiosis/diagnóstico , Anciano , Biopsia , Encéfalo/patología , Absceso Encefálico/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Tumor Carcinoide/patología , Tumor Carcinoide/secundario , Síndrome de Cushing/patología , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/patología , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Nocardiosis/patologíaRESUMEN
This study investigated the binding characteristics of insulin-like growth factor-I (IGF-I) to rat adrenal cells. The binding constants in two regions of the adrenal glands (glomerulosa and fasciculata-reticularis-medulla) were studied separately. In membrane fractions prepared from either region, the binding of iodine 125-labeled IGF-I was demonstrated to be protein and temperature dependent, saturable, and specific. Unlabeled IGF-I was more effective than IGF-II or insulin in displacing 125I-labeled IGF-I binding to the receptor. Fifty percent of the binding was displaced when 2.2, 77.2, or 433.2 nmol/L IGF-I, IGF-II, or insulin, respectively, were added. Receptor numbers and affinity in membrane fractions obtained from either region of the adrenal glands were similar (1821 +/- 188 fmol/mg 1689 +/- 211 fmol/mg protein and a dissociation constant of 1.54 +/- 0.16 nmol/L versus 1.61 +/- 0.13 nmol/L for the glomerulosa and fasciculata-reticularis-medulla regions, respectively). When labeled IGF-I was cross-linked to the binding subunit under reducing conditions, a predominant band with a molecular weight of 135 kd was noted in either region of the adrenal glands. The data indicate that both regions of the rat adrenal glands have specific IGF-I receptors. The binding and the molecular weight characteristics are similar to the "classical" type I IGF receptor. The data are consistent with recent reports suggesting a modulating role for IGF-I in regulating adrenal cell growth and function.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Receptores de Superficie Celular/metabolismo , Marcadores de Afinidad , Animales , Membrana Celular/metabolismo , Reactivos de Enlaces Cruzados , Factor I del Crecimiento Similar a la Insulina/química , Peso Molecular , Ratas , Receptores de Superficie Celular/química , Receptores de SomatomedinaRESUMEN
We investigated the effect of chronic hyperglycemia on glucose transporters in erythrocytes of subjects with and without diabetes mellitus. We found a 22% increase in D-glucose-displaceable cytochalasin-B binding in erythrocyte membranes of diabetic subjects over those of controls (311 +/- 13 vs. 254 +/- 8 pmol/mg protein; P less than 0.001). This increased binding was due to a higher density of binding sites without a significant change in binding affinity. Cytochalasin-B binding to erythrocyte membrane correlated positively with both erythrocyte glycohemoglobin and serum glucose levels, but not with plasma C-peptide levels. The data are compatible with up-regulation of glucose transporters in the erythrocytes of subjects with chronic hyperglycemia. We suspect that this is brought about by increased synthesis and membrane incorporation of the glucose transporter during erythropoiesis.
Asunto(s)
Diabetes Mellitus/sangre , Membrana Eritrocítica/metabolismo , Hiperglucemia/sangre , Proteínas de Transporte de Monosacáridos/sangre , Adulto , Anciano , Glucemia/análisis , Péptido C/sangre , Enfermedad Crónica , Citocalasina B/metabolismo , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Transgenic mice were used to investigate sequences within the promoter of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the rat (EC 4.1.1.32) (PEPCK) which are involved in tissue-specific and developmental regulation of gene expression. Segments of the PEPCK promoter between -2000 and -109 were linked to the structural gene for bovine growth hormone (bGH) and introduced into the germ line of mice by microinjection. Bovine growth hormone mRNA was found in tissues that express the endogenous PEPCK gene, mainly in the liver but to a lesser extent in the kidney, adipose tissue, small intestine, and mammary gland. In the liver the chimeric PEPCK/bGH(460) gene was expressed in periportal cells, which is consistent with the zonation of endogenous PEPCK. The PEPCK/bGH gene was not transcribed in the livers of fetal mice until immediately before birth; at birth the concentration of bGH mRNA increased 200-fold. Our results indicate that the region of the PEPCK promoter from -460 to +73 base pairs contains regulatory sequences required for tissue-specific and developmental regulation of PEPCK gene expression. Mice transgenic for PEPCK/bGH(460) were not hyperglycemic or hyperinsulinemic in response to elevated bGH, as were transgenic mice with the MT/bGH gene. The number of insulin receptors in skeletal muscle was no different in mice transgenic for MT/bGH when compared with mice transgenic for PEPCK/bGH(460) and control animals. However, mRNA abundance for the insulin-sensitive glucose transporter in skeletal muscle was decreased in mice transgenic for the MT/bGH gene. The differences in glucose homeostasis noted with the two types of transgenic mice may be the result of the relative site of expression, the different developmental pattern, or hormonal regulation of expression of the bGH gene.
Asunto(s)
Hormona del Crecimiento/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Receptor de Insulina/metabolismo , Animales , Bovinos , Quimera , Sondas de ADN , ADN Recombinante/metabolismo , Regulación de la Expresión Génica , Genes , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Especificidad de Órganos , Plásmidos , Regiones Promotoras Genéticas , ARN/genética , ARN/aislamiento & purificación , ARN Mensajero/genética , ARN Mensajero/aislamiento & purificación , Ratas , Valores de Referencia , Mapeo RestrictivoRESUMEN
Hypopituitarism is a major manifestation of pituitary adenoma apoplexy. We postulated that the acute deterioration in pituitary function may be caused by compression of portal vessels and the pituitary stalk, secondary to a sudden increase in intrasellar contents. If this were the case, one would predict improvement in pituitary function to occur after surgical decompression. We studied pituitary function in eight patients presenting with the clinical syndrome of pituitary adenoma apoplexy before and on multiple occasions after urgent surgical decompression. Partial or complete hypopituitarism was seen in all subjects at the time of presentation. Serum cortisol levels were inappropriately low (5.9 +/- 1.4 micrograms/dL; 162.8 +/- 38 nmol/L) for the degree of stress in seven patients and appropriately elevated in only one subject (55.3 micrograms/dL; 1525.7 nmol/L). High normal increments in cortisol levels were noted in three subjects given test doses of cosyntropin. Patients were given glucocorticoids before, during, and for 2 days after surgery. Serum cortisol concentrations measured on or after the third day when glucocorticoids had already been stopped were normal in seven subjects and consistently low in one. These seven subjects were discharged on no replacement and were subsequently documented by dynamic testing to have normal pituitary-adrenal function. Gonadal function improved in two of four men and in one of two women who had hypogonadism on presentation. Improvement in thyroid function was documented in two of three subjects with preoperative hypothyroidism. Gradual improvement and almost complete resolution of the neuroophthalmological abnormalities occurred days to weeks after decompression. These observations demonstrate that urgent surgical decompression after pituitary tumor apoplexy was associated with improvement not only in neurological defects but also in pituitary function. The rapid improvement in pituitary function indicates not only that the hypopituitarism was reversible, but also that it might be caused by compression of the portal circulation and pituitary stalk by the sudden increase in intrasellar contents.
Asunto(s)
Trastornos Cerebrovasculares/etiología , Hipopituitarismo/fisiopatología , Neoplasias Hipofisarias/cirugía , Hormona Adrenocorticotrópica/análisis , Adulto , Trastornos Cerebrovasculares/cirugía , Femenino , Hormona Folículo Estimulante/análisis , Hormona del Crecimiento/análisis , Humanos , Hipopituitarismo/etiología , Técnicas para Inmunoenzimas , Hormona Luteinizante/análisis , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/fisiopatología , Prolactina/análisis , Testosterona/sangre , Tirotropina/análisisRESUMEN
The present studies were designed to test the hypothesis that hyperprolactinemia modulates target tissue responsiveness to angiotensin-II (AII). Adrenal and pressor responses to AII infusions were determined in six patients with PRL-secreting pituitary microadenomas and in five normal controls during defined electrolyte balance. Hyperprolactinemic and normal subjects had similar mean blood pressures while on a regular Na intake (82.5 +/- 0.5 vs. 81.2 +/- 0.3 mm Hg). However, after 4 days of Na loading (200 meq/day), the mean blood pressure in hyperprolactinemic subjects was higher than that in normal (86.6 +/- 1 vs. 83.4 +/- 0.8 mm Hg; P less than 0.05). In addition, enhancement of the mean blood pressure response to three doses of AII was noted in hyperprolactinemic subjects (P less than 0.05) compared to that in normal subjects. After 4 days of Na restriction (10 meq/day), the mean blood pressure in hyperprolactinemic subjects was similar to that in normal subjects (79.7 +/- 0.6 vs. 78.9 +/- 1 mm Hg). However, despite adequate Na restriction, the pressor response to AII continued to be enhanced (P less than 0.05) in hyperprolactinemic subjects. There were no differences in plasma or urinary electrolytes or in PRA between hyperprolactinemic and normal subjects. Hyperprolactinemic subjects had higher basal (P less than 0.01), AII-stimulated (P less than 0.05), and ACTH-stimulated (P less than 0.02) aldosterone levels during Na loading, but not during Na restriction. The differences disappeared after the correction of the hyperprolactinemia. The data demonstrate significant alterations in adrenal and pressor responsiveness in hyperprolactinemic subjects and suggest a modulating role for PRL on vascular reactivity and steroid biosynthesis. The precise mechanism has not been determined, but may be secondary to PRL-induced up-regulation of adrenal and vascular AII receptors.
Asunto(s)
Glándulas Suprarrenales/efectos de los fármacos , Angiotensina II/farmacología , Hiperprolactinemia/metabolismo , Prolactina/metabolismo , Adenoma/metabolismo , Glándulas Suprarrenales/metabolismo , Adulto , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Neoplasias Hipofisarias/metabolismo , Potasio/metabolismo , Sodio/metabolismo , Esteroides/biosíntesis , Equilibrio Hidroelectrolítico/efectos de los fármacos , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
Postmenopausal women who underwent modified radical mastectomy for Stage II, estrogen receptor (ER)-positive breast cancer were randomized to receive endocrine treatment (tamoxifen [T], 40 mg daily for 3 years) alone versus endocrine treatment plus five-drug chemotherapy (Cytoxan [cyclophosphamide, C], methotrexate [M], 5-fluorouracil [F], vincristine [V], and prednisone [P], CMFVP, for 1 year). Chemotherapy consisted of oral P (1 month), oral C (12 months), and intravenous MFV weekly for the first 3 months, biweekly for 3 months, and triweekly for 6 months. Patients were entered into the study from October 1979, to October 1985, and the median follow-up is 55 months. Results show that with 94 postmenopausal women, disease-free survival (DFS) is significantly greater (P = 0.04, log-rank test; P = 0.03, multivariate analysis) in patients receiving CMFVPT as compared to those receiving T alone. These results suggest that intensive chemotherapy combined with T is more effective in delaying recurrence than T alone in postmenopausal patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Menopausia , Receptores de Estrógenos/análisis , Tamoxifeno/uso terapéutico , Anciano , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Terapia Combinada , Ciclofosfamida/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Mastectomía Radical Modificada , Metotrexato/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Prednisona/administración & dosificación , Análisis de Supervivencia , Tamoxifeno/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Patients undergoing pituitary adenomectomy are usually given glucocorticoid therapy, although there are no data to document the need for such therapy. We prospectively studied hypothalamic-pituitary-adrenal axis (HPA) function in 88 consecutive pituitary adenoma patients before and after selective adenomectomy, excluding those with corticotroph adenomas. Preoperatively, 5 patients had adrenal insufficiency (AI); they were treated with glucocorticoids and excluded from the analysis. The remaining 83 patients had normal HPA function preoperatively and were not given glucocorticoids before, during, or immediately after surgery, but were closely monitored, and their serum cortisol levels were measured in the immediate postoperative period. Two patients were clinically suspected to have AI postoperatively and were treated accordingly. The remaining 81 patients had no clinical manifestations of AI and received no glucocorticoid therapy. Their serum cortisol levels in the immediate postoperative period were appropriately elevated. The mean serum cortisol level was 40.5 +/- 11.1 (+/- SD) micrograms/dL (1117 +/- 306 nmol/L) 6 h after surgery; serum cortisol levels decreased gradually thereafter. Morning serum cortisol levels were within the normal range on the fourth, fifth, and sixth days after surgery: day 4, 15.1 +/- 7.0 micrograms/dL (417 +/- 193 nmol/L); day 5, 16.4 +/- 5.6 micrograms/dL (453 +/- 155 nmol/L); and day 6, 16.3 +/- 5.7 micrograms/dL (450 +/- 157 nmol/L). When tested 3 months after surgery, all 81 patients had normal HPA function. We conclude that HPA function is rarely compromised after selective pituitary adenomectomy. Close observation and serum cortisol measurements in the immediate postoperative period can reliably predict the integrity of the HPA after surgery. Routine glucocorticoid therapy is not needed in patients undergoing selective adenomectomy whose preoperative adrenal function is normal.
Asunto(s)
Adenoma/cirugía , Glucocorticoides/uso terapéutico , Sistema Hipotálamo-Hipofisario/fisiopatología , Neoplasias Hipofisarias/cirugía , Sistema Hipófiso-Suprarrenal/fisiopatología , Premedicación , Adenoma/sangre , Adenoma/fisiopatología , Adolescente , Adulto , Anciano , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/fisiopatología , Cuidados Posoperatorios , Periodo PosoperatorioRESUMEN
Magnetic resonance imaging (MRI), computed tomographic (CT) scanning, and angiography or digital subtraction angiography (DSA) were used preoperatively to evaluate 16 surgically proven cases of sellar tumor with extrasellar extension. There were 15 pituitary tumors and 1 schwannoma. The capabilities of MRI in evaluating these tumors were compared with CT scanning and angiography. Bone destruction and tumor calcification were better detected by CT scanning than by MRI. MRI was as effective as CT scanning in detecting a cyst or variation in tumor consistency. Neither MRI nor CT scanning was capable of distinguishing specific tumor types. In every case, MRI was superior to CT scanning for delineating spatial relationships of the tumor to the 3rd ventricle, the optic apparatus, adjacent brain, and parasellar vasculature. Vessel encasement by tumor was clearly seen on MRI when there was no direct indication of this on other studies. Cavernous sinus invasion was not demonstrated by CT scanning, but was indicated by MRI in 5 cases and was surgically confirmed in 3. MRI can provide more precise spatial information on extrasellar tumor extension. Vascular encasement and cavernous sinus invasion may be determined preoperatively. Treatment expectations and operative approaches can be guided by this information. When MRI is available, it is the test of choice for the preoperative evaluation of patients with suspected large pituitary gland (sellar region) tumors. Contrast-enhanced CT scanning and angiography can be used as supplementary studies to add information inherently unique to these techniques.