Estruma ovárico asociado con enfermedad de graves / Struma ovarii associated with Graves' disease

El hipertiroidismo se define como la producción excesiva de hormonas tiroideas a partir de tejido tiroideo maduro eutópico o ectópico. La prevalencia general de hipertiroidismo es 1.2%, y la causa más frecuente es la enfermedad de Graves. El estruma ovárico representa el 1% de todos los tumores ováricos y es una causa infrecuente de hipertiroidismo ectópico. Su comportamiento es benigno en más del 90% de los casos; usualmente asintomáticos, sólo el 8% se presentan con tirotoxicosis, y es infrecuente su asociación con enfermedad de Graves. Se comunica el caso de una paciente con esta infrecuente asociación.

Hyperthyroidism is defined as an excessive production of thyroid hormones by eutopic or ectopic mature thyroid tissue. The overall prevalence of hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and only 8% are presented with thyrotoxicosis, being rare its association with Graves' disease. We report the case of a patient with this association.

[Struma ovarii associated with Graves' disease]. / Estruma ovárico asociado con enfermedad de Graves.

Hyperthyroidism is defined as an excessive production of thyroid hormones by eutopic or ectopic mature thyroid tissue. The overall prevalence of hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and only 8% are presented with thyrotoxicosis, being rare its association with Graves' disease. We report the case of a patient with this association.

Treatment and management of epilepsy in the elderly demented patient.

Epilepsy and seizures are more frequent in the elderly population than in any other age group. The number of individuals older than 65 is constantly increasing, and dementia is a process that predominantly affects this age group. Several studies have shown that dementia is an important risk factor for developing seizures and epilepsy. Seizure semiology in the elderly demented might differ from that of younger age groups and diagnosis can be complicated further by the variety of other causes of transient changes of alertness and behavior that affects these patients. The pharmacokinetic changes of antiepileptic drugs in the elderly make this group a major therapeutic challenge. Side effects and drug interactions play a major role in the choice of antiepileptic agents. This review intends to summarize the existing data to see whether this can help guide the clinician in the treatment and management of epilepsy in the elderly patient with dementia. Nonpharmacologic therapeutic options are also briefly considered.

Intravenous lidocaine infusion for the treatment of post-acoustic neuroma resection headache: a case report.

Presentation of a case report of a 47-year-old male with a post-acoustic neuroma resection intractable headache responding to intravenous lidocaine infusion. The patient was then switched to mexiletine, with good response.

Bioequivalence of two levothyroxine tablet formulations without and with mathematical adjustment for basal thyroxine levels in healthy Argentinian volunteers: a single-dose, randomized, open-label, crossover study.

BACKGROUND: Levothyroxine has a narrow therapeutic index; therefore, precise and accurate assessment of the bioequivalence of different levothyroxine products is critical. Bioavailability estimates of levothyroxine formulations might be affected by baseline concentrations of the hormone. OBJECTIVES: The aim of this study was to assess the bioequivalence of 100 microg of a test (T4 Montpellier 100, Química Montpellier S.A., Buenos Aires, Argentina) and reference (Synthroid, Abbott Laboratories, Abbott Park, Illinois) formulation of levothyroxine. We also compared 2 methods of levothyroxine measurements: without and with baseline correction for endogenous levothyroxine. METHODS: This randomized, open-label, 2-sequence, crossover study with a 65-day washout period was carried out in healthy, white, euthyroid volunteers following a single dose of sodium levothyroxine 600 microg. Blood samples were collected at 30 and 15 minutes prior to administration, and 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 hours to determine thyroxine; serum thyrotropin (TSH) concentrations were determined 30 minutes before administration and 48 hours after administration. Serum concentrations of thyroxine were determined through radioimmunoassay and serum TSH concentrations were determined by a validated 2-site immunoradiometric assay. The formulations are considered to be equivalent if the 90% CI ratios for C(max) and AUC(0-last) are within 80% to 125%, per the US Food and Drug Administration (FDA). Adverse event monitoring was performed throughout the study by assessing clinical parameters (eg, blood pressure, electrocardiogram) and patient reports. RESULTS: A total of 24 volunteers (16 male, 8 female; mean [SD] age, 30.2 [4.6] years [range, 21-40 years]; mean [SD] weight, 71.71 [7.52] kg [range, 58-83 kg]) were included in the study. Without adjustment for baseline levels of endogenous levothyroxine, geometric mean C(max) for the test and reference formulations were 8.92 and 9.39 microg/dL, respectively; AUC(0-last) values were 368.40 and 383.37 microg/mL . h(-1). The 90% CI of the geometric mean for the percent ratios (test: reference) of C(max) and AUC(0-last) were 95.1% (90% CI, 91.9-98.3) and 96.1% (90% CI, 94.0-98.2), respectively. With adjustment for baseline levels of endogenous levothyroxine, the geometric mean C(max) for the test and reference formulations were 3.16 and 3.39 microg/dL, respectively; AUC(0-last) values were 88.33 and 95.60 microg/mL . h(-1). Despite performing the adjustment, the 90% CI of the geometric mean for Cmax and AUC(0-last) test:reference ratios were 93.1% (90% CI, 84.9-102.2) and 92.4% (90% CI, 85.2-100.2), respectively. No significant between-group differences were found with regard to pharmacokinetic parameters. No adverse events were observed or reported. CONCLUSION: The results of this study suggest that the test formulation was bioequivalent to the reference formulation of levothyroxine in these healthy volunteers, according to the US FDA definition of bioequivalence. This was supported by the analysis of concentration-time profiles without and with correction for basal endogenous levothyroxine.

Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects.

OBJECTIVE: the aim of this relative bioavailability study was to determine the rate and extent of absorption of Alikal Dolor (effervescent powder containing paracetamol 500 mg/sodium bicarbonate 2318 mg)--test formulation (T) in relation to Parageniol (paracetamol 500 mg coated tablets)--reference formulation (R). METHODS: 18 healthy volunteers (10 male and 8 female aged between 21 and 46 years) received, after 2 h of standardized breakfast, a single oral dose with 220 ml of water, in an open, randomized, crossover study, with a 7-day wash-out period. Paracetamol concentrations were established at 0, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 75, 90 min and at 2, 4, 6, 8 and 10 h postdose by HPLC with an ultraviolet detector. RESULTS: the regression coefficient determined for paracetamol calibration curves was 0.9983 +/- 0.0034 and the working range was from 0.2 to 50 microg/ml. The quantification limit was 0.2 microg/ml. The rate of absorption was significantly greater (p < 0.03) for T (T(max) = 20.4 min) compared with R (T(max) = 38.4 min). Extent of absorption over the first 30 min postdose AUC((0-30 min)) was 4.21-fold greater (p < 0.03) for T compared with R, without differences between C(max.) The 90% CI on the geometric mean for C(max), AUC((0-10 h)) and AUC((0-)) ratios (T/R) were within the limits of 0.80-1.25, indicating both formulations were bioequivalent with respect to these parameters. CONCLUSION: paracetamol was absorbed at least twice as fast from T-containing sodium bicarbonate compared with R. This pharmacokinetic feature could prove crucial from the therapeutic point of view as it would allow a lower latency in the action time of paracetamol in producing its analgesic and antithermal effect.

Parent drug and/or metabolite? Which of them is most appropriate to establish bioequivalence of two oral oxcarbazepine formulations in healthy volunteers?

The bioequivalence of two 600-mg oxcarbazepine oral formulations (Aurene, Ivax Argentina, [test]; and Trileptal, Novartis Laboratories, [reference]) were assessed through the simultaneous determination of oxcarbazepine and the active metabolite 10,11-dyhydro-10-hydroxy-carbamazepine derivative (MHD). 12 healthy male volunteers received a single oral dose of 600 mg of each formulation, in a balanced, randomized, paired, crossover design, with a 7-day wash out period. Oxcarbazepine and MHD concentrations were established at 0.5,1, 1.5, 2, 3, 4, 6, 8, 24 and 48 h post dose by high performance liquid chromatography (HPLC). The regression coefficient determined for oxcarbazepine calibration curves was 0.9933 +/- 0.0236; and for MHD, was 0.9897 +/- 0.0017. The working range for both oxcarbazepine and its metabolite was from 0.1 to 10.0 microg/ml. The quantification limit was 0.1 microg/ml. The 90% confidence interval (CI) geometric mean for oxcarbazepine C(max), AUC(0-48 h) and AUC(0-infinity) ratios (test : reference) were 74.1-146.2%, 85.6-171.5% and 89.6-169.8%, respectively, and the 90% CI geometric mean for MHD C(max), AUC(0-48 h) and AUC(0-infinity) ratios (test : reference) were 84.0-122.3, 93.2-117.9 and 96.5-116.7, respectively. These results established the bioequivalence of two oxcarbazepine formulations from MHD kinetic data used in 12 healthy volunteers, while it was not possible to establish bioequivalence with oxcarbazepine. MHD quantification is preferred to that of the oxcarbazepine in order to assess bioequivalence, as the metabolite is responsible for the antiepileptic activity, presents linear kinetics in the therapeutic range, has lower intra-individual variability and higher plasma levels and half life than the parent drug.

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma.

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI) dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RI therapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin (Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease. Median follow-up after the first rhTSH-aided radioiodine treatment was 32 +/- 13 months (range 8 to 54 months). Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. In conclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients (GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels.

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels. (AU)

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes. (AU)

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels. (AU)

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes. (AU)

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels.

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes.