RESUMEN
OBJECTIVE: Approximately one out of five patients with Graves' disease (GD) undergoes a thyroidectomy after a mean period of 18 months of medical treatment. This retrospective and non-randomized study from a teaching hospital compares short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for this disease. METHODS: From 1987 to 1997, 94 patients were operated for GD. Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4 to 8 grams of thyroid tissue--mean 6 g). All patients had received propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time of surgery; they also took potassium iodide (lugol) for ten days before surgery. RESULTS: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32 patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two patients developed transient recurrent laryngeal nerve palsy after ST (< 3 months). After a median follow-up period of seven years (1-15) with five patients lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%), thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism, requiring completion of thyroidectomy. All 33 patients having had TT--with follow-ups averaging two years (0.5-8)--are receiving thyroxin substitution. CONCLUSIONS: There were no instances of persistent recurrent laryngeal nerve palsy in either group, but persistent hypoparathyroidism occurred more frequently after TT. Long after ST, hypothyroidism developed in nearly three of four cases, whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was rare.
Asunto(s)
Enfermedad de Graves/cirugía , Complicaciones Posoperatorias/etiología , Tiroidectomía , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pruebas de Función de la TiroidesRESUMEN
PURPOSE: We wished to determine the incidence of first provoked and nonprovoked epileptic seizures in the canton of Geneva, Switzerland. METHODS: Between June 1, 1990 and May 31, 1991, we collected all cases of suspected epileptic seizures referred to the two hospitals of the county of Geneva, Switzerland and to the private neurologists of the town. The diagnosis probability was based on clinical data from the patient chart and the EEG data. The classification of risk factors proposed by the International League Against Epilepsy (ILAE) Commission on Epidemiology and Prognosis was used. RESULTS: In all, 273 cases were collected. The age-adjusted incidence rate (U.S. population as standard) is 69.4 in 100,000. We observed a bimodal distribution of the cases with age (71 in the group aged 0-10 years and 107.5 in those aged > 60 years). Ninety-seven cases were classified as having provoked seizures (incidence: 25.2 in 100,000). Alcohol consumption (29.8%) and cerebrovascular diseases were the most frequent causes (16.4%). One hundred seventy-six cases were classified as having unprovoked seizures (incidence: 45.6 in 100,000) with the following distribution: seizures in relation with a stable cerebral condition, 69 cases (incidence: 17.9); seizures in relation with an evolutive cerebral condition, 27 cases (incidence: 7); and seizures of unknown etiology, 80 cases (incidence: 20.8). CONCLUSIONS: The incidence rate of first epileptic seizures in the canton of Geneva is quite similar to that reported in a French study (Epilepsia (1990;31:391-394) in which the same methodology for case ascertainment was used. Our data clearly demonstrate that the classification of risk factors proposed by the ILAE Commission on Epidemiology and Prognosis is useful and particularly easy to use in epidemiological surveys.
Asunto(s)
Epilepsia/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Electroencefalografía/estadística & datos numéricos , Métodos Epidemiológicos , Epilepsia/clasificación , Epilepsia/diagnóstico , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores de Riesgo , Distribución por Sexo , Suiza/epidemiologíaAsunto(s)
Encefalopatía Hepática/complicaciones , Trasplante de Hígado , Estado Epiléptico/etiología , Encéfalo/diagnóstico por imagen , Daño Encefálico Crónico/etiología , Várices Esofágicas y Gástricas/cirugía , Encefalopatía Hepática/diagnóstico por imagen , Encefalopatía Hepática/cirugía , Síndrome Hepatorrenal/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Derivación Portosistémica Intrahepática Transyugular , Estado Epiléptico/diagnóstico por imagen , Tomografía Computarizada de Emisión , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Thyroid hormones act by binding to nuclear receptor proteins, the thyroid hormone receptors (TR) alpha and beta. Data from cell culture and animal studies indicate that TR expression may be regulated to modulate target organ responsiveness to thyroid hormone. To investigate whether such adaptive changes in TR expression occur in humans, we determined the mRNA levels of the hTR beta 1 in various thyroid states. Patients with overt hypo- or hyperthyroidism were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells and hTR beta 1 mRNA levels determined by quantitative competitive reverse transcription PCR. For comparison, hTR beta 1 mRNA levels were determined in lymphocytes and normal thyroid tissue of euthyroid patients. Human TR beta 1 mRNA levels in lymphocytes were 1.8 +/- 0.4, 1.9 +/- 0.5, 1.1 +/- 0.4 10(-18) mol/microgram RNA in hypo-, eu- and hyperthyroid patients, respectively, corresponding to an estimated 0.5 - 2 molecules per cell. Although the mean hTR beta 1 mRNA levels were 40% lower in hyperthyroid than in euthyroid subjects, this difference did not reach statistical significance. Similar levels of hTR beta 1 mRNA levels were detected in thyroid gland from euthyroid patients. In summary, we developed an assay for the quantitative determination of hTR beta 1 mRNA levels in small human tissue samples, containing as little as 50 ng of total RNA. Absolute hTR beta 1 mRNA levels are very low with an estimated one molecule of mRNA being present in a mononuclear blood cell or thyrocyte. No up-regulation of hTR beta 1 was seen in hypothyroid relative to euthyroid patients. However, there is a non-significant trend towards a down-regulation of hTR beta 1 mRNA levels in hyperthyroid patients.
Asunto(s)
Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Receptores de Hormona Tiroidea/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Unión Competitiva , Femenino , Humanos , Linfocitos/química , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , ADN Polimerasa Dirigida por ARN , Glándula Tiroides/químicaRESUMEN
We found in preliminary experiments that multiple daily injections of triiodothyronine (T3) resulted in an apparent prolongation in the half time (t1/2) of mRNA-S14 decay. To appropriately interpret these observations, we developed a mathematical model of the fluctuations of mRNA-S14 and its nuclear precursor after a single injection or multiple daily injections of T3. The model parameters include 1) the effect of plasma protein binding and metabolic clearance rates on receptor-bound nuclear T3, 2) the threefold circadian variation in mRNA-S14, 3) a 12-min t1/2 for the nuclear precursor and a 1.5-h t1/2 for the mature mRNA-S14, 4) previously derived relationships between the level of plasma T3 and nuclear occupancy, and 5) direct proportionality between nuclear transcription of the S14 gene and T3 nuclear occupancy. The model faithfully predicted the excursions of the mature mRNA-S14 and its nuclear precursor. Nuclear retention of T3 and the effects of circadian variation on S14 gene transcription explain the apparent prolongation in the t1/2 of decay of mature mRNA. Our findings illustrate the feasibility of incorporating parameters at the molecular level into a comprehensive kinetic analysis of hormone action.
Asunto(s)
Hígado/metabolismo , Modelos Biológicos , Precursores de Proteínas/genética , Proteínas/genética , ARN Mensajero/metabolismo , Triyodotironina/farmacología , Animales , Esquema de Medicación , Semivida , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Inyecciones , Cinética , Masculino , Proteínas Nucleares , Ratas , Ratas Sprague-Dawley , Factores de Transcripción , Triyodotironina/administración & dosificaciónRESUMEN
6 years after surgery for epidermoid lung cancer, a 58-year-old man presented with atopic dermatitis and a high level of IgE, primary hypothyroidism of autoimmune origin, slight hyperprolactinemia and adrenal insufficiency of pituitary origin. ACTH levels were low and unresponsive to CRH. There was no deficiency of the other pituitary hormones and the MRI of the pituitary was normal. The other instances of autoimmune thyroiditis associated with ACTH deficiency are reviewed. The etiology of the deficiency is discussed in the context of a possible hypophysitis.
Asunto(s)
Hormona Adrenocorticotrópica/deficiencia , Dermatitis Atópica/complicaciones , Hipopituitarismo/complicaciones , Hipotiroidismo/etiología , Tiroiditis Autoinmune/complicaciones , Cortisona/uso terapéutico , Dermatitis Atópica/diagnóstico , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamiento farmacológico , Hipotiroidismo/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pruebas de Función Hipofisaria , Tiroiditis Autoinmune/diagnóstico , Tiroxina/uso terapéuticoRESUMEN
Hypothyroidism followed by hyperthyroidism is described in two patients treated by amiodarone. Euthyroidism was rapidly restored after treatment with antithyroid drugs and potassium perchlorate. The physiopathology of amiodarone-induced hypothyroidism is discussed. Withdrawal of amiodarone is advised in the case of both hypothyroidism and hyperthyroidism.
Asunto(s)
Amiodarona/efectos adversos , Hipertiroidismo/inducido químicamente , Hipotiroidismo/inducido químicamente , Anciano , Anciano de 80 o más Años , Antitiroideos/uso terapéutico , Femenino , Humanos , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/fisiopatología , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/fisiopatología , Masculino , Persona de Mediana Edad , Percloratos/uso terapéutico , Compuestos de Potasio/uso terapéuticoRESUMEN
We have compared the dose of levothyroxine (L-T4) required to suppress serum TSH to given levels in two clinical groups: 1) 44 patients with thyroid cancer whose thyroid glands had been ablated by surgical thyroidectomy and 131I treatment, and 2) 113 patients with thyroidal failure due either to spontaneous primary hypothyroidism (31 patients) or after 131I treatment for Graves' hyperthyroidism (82 patients). The dose of L-T4 needed to attain serum TSH levels in the euthyroid range (0.5-6.2 microU/mL) was significantly greater (P less than 0.01) in patients with thyroid cancer (2.11 micrograms/kg.day) than in the patients with primary hypothyroidism associated with nonmalignant disease (1.63 micrograms/kg.day). Similarly, patients with thyroid cancer required a higher dose of L-T4 to suppress serum TSH to a given subnormal level. These findings suggest that the secretion of hormone from residual thyroid tissue in patients who have not been subjected to near-total thyroid ablation contributes substantially to the circulating levels of serum T4 and T3. We, therefore, infer that residual thyroidal secretion in the patients with hypothyroidism due to benign causes is relatively independent of TSH stimulation. Further subdivision of patients with benign hypothyroidism revealed that patients with Graves' who developed hypothyroidism after 131I treatment showed a lower mean dose requirement than patients with spontaneous hypothyroidism. This raises the possibility that continued secretion of thyroid-stimulating immunoglobulin in such patients might account for the lower dose requirement in the combined group with hypothyroidism. Our studies also have allowed us to make serial observations in 4 patients with thyroid cancer who exhibited elevated levels of serum thyroglobulin. In this limited series, maximal suppression of serum thyroglobulin was produced by doses of L-T4, which reduced circulating TSH to 0.4 mU/L.
Asunto(s)
Neoplasias de la Tiroides/tratamiento farmacológico , Tirotropina/antagonistas & inhibidores , Tiroxina/uso terapéutico , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Concentración Osmolar , Hormonas Tiroideas/sangre , Neoplasias de la Tiroides/sangre , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
During the period of life that precedes weaning, the facial nucleus of the newborn rat is rich in 3H-vasopressin binding sites, and exogenous arginine vasopressin (AVP) can excite facial motoneurons by interacting with V1 (vasopressor-type) receptors. We have investigated the mode of action of this peptide by carrying out single-electrode voltage-clamp recordings in coronal brainstem slices from the neonate. Facial motoneurons were identified by antidromic invasion following electrical stimulation of the genu of the facial nerve. When the membrane potential was held at or near its resting level, vasopressin generated an inward current whose magnitude was concentration related; the lowest peptide concentration still effective in eliciting this effect was 10 nM. The vasopressin-induced current, IAVP, was resistant to tetrodotoxin (TTX) and was insensitive to a reduction in extracellular calcium concentration. It was sustained, was inward at all potentials tested (-120 to -25 mV), and increased in magnitude during depolarization. IAVP was not generated by the blockade of a potassium current, because it did not reverse at hyperpolarized potentials, was not affected by a two-fold increase in the transmembrane potassium gradient, and was not modified by the potassium channel blockers tetraethylammonium bromide (TEA), 4-aminopyridin (4-AP), barium, cesium, quinine, glibenclamide, and apamin. Also, IAVP was not affected by changes in the transmembrane chloride gradient. In contrast, it could be reduced by partially substituting extracellular sodium with equimolar N-methyl-D-glucamine or Tris. Our results suggest that vasopressin increases the excitability of facial motoneurons by generating a persistent sodium-dependent membrane current that is voltage gated and TTX resistant.
Asunto(s)
Arginina Vasopresina/farmacología , Tronco Encefálico/fisiología , Nervio Facial/fisiología , Neuronas Motoras/fisiología , Canales de Sodio/fisiología , Animales , Animales Recién Nacidos , Arginina Vasopresina/metabolismo , Conductividad Eléctrica/efectos de los fármacos , Estimulación Eléctrica , Nervio Facial/efectos de los fármacos , Técnicas In Vitro , Cinética , Masculino , Potenciales de la Membrana/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Ratas , Ratas Endogámicas , Receptores de Angiotensina/metabolismo , Receptores de Angiotensina/fisiología , Receptores de Vasopresinas , Canales de Sodio/efectos de los fármacos , Tetrodotoxina/farmacologíaRESUMEN
Binding sites for AVP and for OT were studied by in vitro autoradiography in sections from the brain of rat fetuses, neonates and infants; their distribution was compared to that of the brain of adults. Specific binding sites were first detected in the vagal complex for OT and in the reticular formation for AVP at E14 and E16 respectively. In the perinatal period, other areas become labeled. Approximately one week after birth, a "stable" pattern of distribution is established for AVP binding sites, and a different "stable" pattern obtained for OT binding sites. For both types of sites and in many areas, the density of labeling increases during the next two weeks to reach adult levels, whereas labeling decreases concomitantly in other areas of the brain. The distribution of AVP binding sites is of the adult pattern by the time of weaning. In contrast, the adult pattern of distribution of OT binding sites is only established after puberty, when new OT receptors appear in some regions of the hypothalamus and basal forebrain. "Transient" binding sites for AVP and OT, i.e. sites located in areas which were labeled in neonates but not in weanlings, were shown to have the same ligand affinity than the binding sites present in the adult. Electrophysiological studies suggest that at least some of these "transient" binding sites represent authentic receptors and may be involved in neuronal signaling.
Asunto(s)
Química Encefálica/fisiología , Oxitocina/fisiología , Receptores de Angiotensina/biosíntesis , Vasopresinas/fisiología , Animales , Animales Recién Nacidos/metabolismo , Autorradiografía , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Ratas , Receptores de Oxitocina , Receptores de VasopresinasRESUMEN
The development of vasopressin (AVP) receptors in the rat brain, spinal cord and pituitary gland was studied by in vitro light microscopic autoradiography. AVP binding sites were labeled using [3H]AVP in tissue sections from animals aged between embryonic day 12 (E12) and postnatal day 90 (PN90); the binding of [3H]AVP to oxytocin receptors was prevented by adding in the incubation medium a highly selective oxytocin agonist. Specific binding was first detected at E16 in the ventral pontine reticular formation. Many other brain areas were progressively labeled between E18 and PN5. The distribution of binding sites observed at PN5 remained unchanged until the beginning of the third postnatal week. Thereafter binding was markedly reduced or even disappeared in several areas, in particular in the facial nucleus. The adult distribution of AVP binding sites was established at the time of weaning. The properties of transient AVP binding sites in the facial nucleus were studied both by autoradiography and by electrophysiology. Non-radioactive AVP displaced [3H]AVP binding in this nucleus as efficiently as it did in the lateral septum of the adult. Single-unit extracellular recordings showed that AVP can excite facial motoneurones by interacting with receptors which are pharmacologically indistinguishable from V1 (vasopressor) type. Thus, AVP binding sites transiently expressed in the brain of fetal and infant rat probably represent functional neuronal receptors, having the same ligand selectivity and affinity than AVP binding sites present in the adult. This suggests that AVP acts not only as a neuropeptide in the adult brain but may play a significant role during maturation of the central nervous system.
Asunto(s)
Animales Recién Nacidos/metabolismo , Arginina Vasopresina/metabolismo , Química Encefálica/fisiología , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Receptores de Angiotensina/metabolismo , Potenciales de Acción/fisiología , Animales , Autorradiografía , Tronco Encefálico/fisiología , Feto/metabolismo , Técnicas In Vitro , Hipófisis/metabolismo , Ratas , Ratas Endogámicas , Receptores de Vasopresinas , Factores de TiempoRESUMEN
T4 and reverse T3 (rT3) can inhibit 5'-deiodinase type II activity in rat brain cortex, pituitary, and brown adipose tissue, raising the possibility that T4 may act in vivo after conversion to rT3. The aim of this study was to measure in hypothyroid (Tx) rats the content of brain cortex rT3 during a constant 7-day infusion of either [125I]T4 alone, corresponding to 12 pmol T4/day X 100 g body weight (BW), or together with 400 pmol T4/day. [125I]T4, rT3, and T3 were extracted from brain cortex, pituitary, kidney, and liver with a combination of adsorption chromatography on Sephadex G-25, HPLC, and immunoprecipitation. [131I]T4, T3, or rT3 were used as internal standards. [125I]rT3 could be detected in brain cortex, liver, and kidney in Tx rats infused with [125I]T4 (12 pmol T4/day X 100 g BW) and in those infused with 400 pmol T4/day X 100 g BW. The highest rT3 concentrations were found in brain cortex, where it represented 6% to 10.5% of the local T4 concentration. During an infusion of 400 pmol T4/day X 100 g BW, brain cortex T3 concentration was 6 times higher in the brain cortex than in serum, and even exceeded that of T4. In Tx rats receiving [125I]T4 alone the brain cortex to serum T3 ratio was 3:1, but the total serum T3 concentration, measured by RIA, was much higher than that due to conversion [0.50 +/- (SE) 0.1 pmol/ml vs. 0.018 +/- 0.002 pmol T3/ml], indicating thyroidal secretion. The effect of the blood-brain barrier on rT3 was measured by infusing [125I]rT3 over 4 days. After killing, rT3 was isolated as above. Approximately 3% of serum rT3 was retrieved from the brain cortex, whereas during the T4 infusion 40-50% of serum rT3 was found demonstrating that brain cortex rT3 is locally produced.
Asunto(s)
Corteza Cerebral/metabolismo , Tiroxina/farmacología , Triyodotironina Inversa/metabolismo , Triyodotironina/metabolismo , Animales , Barrera Hematoencefálica , Corteza Cerebral/efectos de los fármacos , Hipotiroidismo/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Masculino , Hipófisis/metabolismo , Ratas , Ratas Endogámicas , Tiroidectomía , Distribución Tisular , Triyodotironina Inversa/farmacologíaRESUMEN
The induction of mixed function hepatic oxygenases by rifampicin is known to increase the metabolic clearance rate (MCR) of T4. By performing T3 and rT3 kinetics we have shown that rifampicin also increases the MCR of T3 and rT3. Using the fall of serum T4 during TSH suppression as an indirect marker of the production rate (PR) of T4, we have demonstrated that there was no major change in monodeiodination nor any shift to either 5'- or 5-monodeiodination. Rifampicin stimulates in mice the mixed function hepatic oxygenases. However, we were unable to increase hepatic deiodinase activity (deiodinase type I) in this species. It is therefore possible that the increased MCR of T4 in man is not mediated by an increased conversion rate either. As mixed function hepatic oxygenases are known to increase hepatic conjugation it is suggested that rifampicin increases the biliary excretion of iodothyronine conjugates.
Asunto(s)
Rifampin/farmacología , Hormonas Tiroideas/metabolismo , Adulto , Animales , Diyodotironinas/uso terapéutico , Humanos , Yoduro Peroxidasa/metabolismo , Cinética , Hígado/enzimología , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Ratones , Tirotropina/metabolismo , Tiroxina/metabolismo , Triyodotironina/metabolismo , Triyodotironina Inversa/metabolismoRESUMEN
To study the effect of rT3 on the 5'-deiodinase type II (5'D-II) of rat brain cortex and anterior pituitary, daily infusions of rT3 at rates of 0.5, 1.5, 4.5, and 13.5 nmol/day X 100 g body weight were given to a total of 87 hypothyroid rats. rT3 inhibited the 5'D-II activity in the total homogenate and in the microsomal fraction in the brain cortex, inhibition becoming significant (28-33%) with the infusion of 4.5 nmol/day X 100 g body weight, at serum levels of 2.4 pmol rT3/ml. Infusion of 13.5 nmol/day X 100 g body weight produced 71-73% inhibition. In homogenates of the anterior pituitary, inhibition was significant with infusions of 13.5 nmol/day X 100 g body weight (30%). To examine how rT3 might inhibit 5'D-II activity, labeled rT3 (137 muCi/day) was infused into 4 hypothyroid rats, and the rT3 content in the homogenate and in the cell subfractions was measured by HPLC. No rT3 was detectable in the nuclei, and less than 1% was found in the microsomal fraction. The infused rT3 was thus no longer present in the microsome preparations and homogenates. The inhibitory effect of rT3 was also compared with that of T4. Serum T4 levels of 45 pmol/ml were required in order to inhibit 5'D-II to the same extent as with 7 pmol rT3/ml. The requirement of this high serum level of T4 excludes the potential role of T4 impurities in the infused rT3 preparation. We therefore conclude that rT3 inhibits 5'D-II in brain cortex per se independently of T4.