Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin

It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i) determine reference ranges for serum testosterone (T) and sex hormone binding globulin (SHBG) appropriate to our laboratory and population, and (ii) to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a) 30 selected non-hyperandrogenic women, (b) 87 non-selected healthy female blood donors, (c) 53 women with hyperandrogenism, and (d) 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a). Using our results for this selected control group as new reference values, 12 out of 38 (31.6%) women with hyperandrogenic disorders without apparent hyperandrogenemia (group d) were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4%) non-selected, normal weight, women (group b), were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.(AU)

Con frecuencia los valores de referencia utilizados para las evaluaciones bioquímicas endocrinológicas son los sugeridos por los kits utilizados, a pesar de las recomendaciones de que cada laboratorio debiera obtener sus propios valores de normalidad. Nuestros objetivos fueron (i) analizar los rangos de referencia para testosterona (T) y globulina ligadora de esteroides sexuales (SHBG) apropiados para nuestro laboratorio y población, y (ii) analizar su influencia en la evaluación de la hiperandrogenemia. Se midió T y SHBG y se calculó testosterona libre y biodisponible en un grupo (a) control de 30 mujeres no hiperandrogénicas, (b) 87 mujeres no seleccionadas donantes de sangre, (c) 53 mujeres con hiperandrogenismo, y (d) 38 mujeres con desórdenes hiperandrogénicos pero sin hiperandrogenemia de acuerdo a los rangos de normalidad sugeridos por el kit. La concentración media de SHBG fue significativamente diferente entre los cuatro grupos. Los niveles de SHBG fueron significativamente más altos en las mujeres controles seleccionadas (grupo a). Tomando en consideración los resultados obtenidos en este grupo y estableciendo los rangos de referencia adecuados, 12 de 38 mujeres (31.6%) hiperandrogénicas sin hiperandrogenemia (grupo d) fueron recategorizadas como con exceso androgénico bioquímico. De igual manera, al analizar mujeres normopesas no seleccionadas, en edad reproductiva (grupo b), 4 de 63 (6.4%) pudieron ser definidas como hiperandrogénicas. Utilizando valores adecuados de referencia para SHBG, se mejora la precisión del diagnóstico de exceso androgénico.(AU)

Pseudo-tumor pituitario e hipopituitarismo secundario a un papiloma invertido del seno esfenoidal / Pseudo-pituitary tumor and hypopituitarism secondary to a sphenoid sinus inverted papilloma

El papiloma invertido (PI) es un tumor epitelial benigno, poco frecuente, que se origina mayormente de la pared nasal lateral. A pesar de ser benigno, constituye una lesión altamente invasiva de tejidos vecinos y puede sufrir una transformación maligna. El PI primario del seno esfenoidal con extensión intracraneana e invasión dural, aun sin evidencia histológica de malignidad, ha sido excepcionalmente descrito. Describimos el caso de una mujer de 59 años de edad que fue evaluada por cefaleas intensas de 5 años de evolución y anormalidades del campo visual. Una resonancia magnética nuclear (RMN) mostró una masa selar heterogénea de 1.4 por 2 cm con extensión supraselar y al seno esfenoidal, con erosión del piso selar y compresión del quiasma óptico. Recibió 16 mg/día de prednisona durante aproximadamente 3 meses con una regresión casi total de la masa en la RMN. En la evaluación hormonal se halló insuficiencia gonadal, tiroidea y adrenal central. En una nueva RMN se observó crecimiento del tumor con compromiso total del seno esfenoidal. Una biopsia endoscópica confirmó el diagnóstico de PI. Se realizó una cirugía sinusal transnasal endoscópica con una resección completa evidenciada en una RMN un año más tarde.(AU)

nverted papilloma (IP) is a benign uncommon epithelial tumor, arising mostly from the lateral nasal wall. Though benign, this lesion is highly invasive into surrounding tissues and malignant transformation may occur. Primary IP of the sphenoid sinus and intracranial extension with dural invasion, even without histological evidence of malignancy, has only rarely been described. Hypopituitarism as a complication of this lesion has never been reported. We describe the case of a 59-year-old woman who was evaluated because of a 5-year-history of severe headaches and abnormalities in the visual field. Magnetic resonance imaging (MRI) showed a 1.4 per 2.0 cm heterogeneous sellar lesion with suprasellar and sphenoid sinus extension, eroding the sellar floor with optic chiasm compression. Otolaryngologists gave her 16 mg/day of prednisone during approximately 3 months with a near total regression of the mass on MRI. The endocrine biochemical evaluation showed pituitary gonadal, thyroid and adrenal insufficiency. A new MRI showed growth of the tumor with obliteration of the sphenoid sinus. An endoscopic sinus biopsy revealed an IP, so a transnasal endoscopic sinus surgery was performed with complete resection evidenced by MRI a year later.(AU)

Medición de cortisol y sus fracciones. Una puesta al día / [A critical analysis of cortisol measurements: an update].

Serum cortisol measurement is a very useful tool in the biochemical evaluation of adrenocortical function. Since this hormone circulates in blood mainly linked to binding globulins but is also partially free, it can be measured not only in the blood but also in urine, saliva and other biological fluids and tissues. Basal determinations as well as dynamic testing may be performed to evaluate the circadian variations, to estimate the diurnal cortisol secretion and to analyze its relations with other components of the hypothalamic-pituitary-adrenal axis. Measurements of cortisol in blood, saliva and urine may reflect the cortisol secretion at the time of sample collection or during a 24 h span. Recently, it has been proposed the determination of cortisol in tissues such as hair and nails like a means of evaluating the hormonal status during prolonged periods. The aim of this paper is to update the methodology for measuring cortisol and its usefulness for the clinical diagnosis of troubles of the hypothalamic-pituitary-adrenal axis.

Low-dose glucocorticoids in hyperandrogenism / Efecto de bajas dosis de glucocorticoides en el hiperandrogenismo

To investigate the effect of low-doses of glucocorticoids on androgen and cortisol secretion during the course of the day, we evaluated clinical signs of hyperandrogenism and total, free and bioavailable testosterone, SHBG, and cortisol following two different protocols: A) fourteen patients received betamethasone 0.6 mg/day (n=8) or methylprednisolone 4 mg/day (n=6), as single daily oral dose at 11.00 PM, during 30 days, B) fourteen patients were evaluated under betamethasone 0.3 mg in a single daily dose at 11.00 PM during six months, 11 out of whom were re-evaluated six months later. Twenty eight women with hyperandrogenism were included and seven normal females were used as control. Blood samples were taken in follicular phase at 8 AM and 7 PM to determine SHBG, cortisol, total, free and bioavailable testosterone. In both protocols, a significant morning and evening decrease in cortisol and testosterone (p<0.05 to < 0.01), which was moremarked with betamethasone (p<0.05), was shown. In protocol B, morning SHBG levels showed a significant increase (p<0.05) and betamethasone also improved clinical hyperandrogenism along the trial. Although morning and evening cortisol significantly decreased during treatment, no side effects were reported. The 11 patients reevaluated after therapy withdrawal, showed a rise in serum total testosterone and its fractions to pre-treatment values and a normalization of cortisol levels. It is concluded that glucocorticoids in low-doses effectively normalize serum androgens, independently of their origin. They may be used therapeutically, mainly whenever a hyperandrogenic woman presents with cycle irregularities or seeking fertility.(AU)

Con el objetivo de investigar el efecto de bajas dosis de glucocorticoides sobre la secreción de andrógenos y cortisol en el curso del día, evaluamos signos de hiperandrogenismo, testosterona total, libre y biodisponible y cortisol según dos protocolos diferentes: A) catorce pacientes recibieron betametasona 0.6 mg/día (n= 8) o metilprednisolona 4 mg/día (n= 6) en dosis única cotidiana, a las 23 h, durante 30 días, B) catorce pacientes fueron evaluadas bajo betametasona 0.3 mg en dosis única cotidiana a la 23 h, administrada durante 6 meses; de ellas, 11 pacientes fueron re-evaluadas 6 meses más tarde. Se incluyeron 28 mujeres con hiperandrogenismo y 7 controles normales. Se obtuvieron muestras de sangre en fase folicular a las 08:00 y 9:00 h para determinar SHBG, cortisol, testosterona total, libre y biodisponible. En ambos protocolos se observó una disminución significativa de cortisol y testosterona (p<0.05 a <0.01), más importante con betametasona (p<0.05). En el protocolo B, los niveles matutinos de SHBG aumentaron significativamente (p<0.05) y se observó mejoría clínica con el tratamiento. Aunque los niveles matutinos y vespertinos de cortisol disminuyeron significativamente durante el tratamiento, no se observaron efectos secundarios. En las 11 pacientes reevaluadas luego de suspensión de glucocorticoides se observó un aumento de testosterona y sus fracciones a los niveles pre-tratamiento con normalización de las concentraciones de cortisol. Dosis bajas de glucocorticoides normalizaron eficazmente los andrógenos séricos elevados, independientemente de su causa. Pueden emplearse terapéuticamente, en especial cuando una mujer hiperandrogénica presenta alteraciones del ciclo menstrual o busca fertilidad.(AU)

Estudio de 34 pacientes con incidentaloma suprarrenal / A study of 34 cases of adrenal incidentaloma

El incidentaloma suprarrenal, un tumor de dicha glándula descubierto por razones independientes de la sospecha de enfermedad adrenal, constituye un problema clínico frecuente. Aunque en la mayoría de los casos son benignos y no hiperfuncionantes, es importante identificar oportunamente la minoría de lesiones malignas o hiperfuncionantes de resolución quirúrgica. Si bien han sido diseñadas distintas estrategias de diagnóstico hay controversia alrededor de una serie de cuestiones. En el presente trabajo retrospectivo once (32%) de nuestros 34 pacientes presentaban masas adrenales hiperfuncionantes manifestadas por síndrome de Cushing subclínico en cuatro, feocromocitoma en tres, probable hiperaldosteronismo primario en dos y por hiperplasia adrenal congénita de origen tardío y carcinoma funcionante en los dos restantes. Las características de las imágenes por TAC y/o RM permitieron identificar los adenomas a la vez que decidir la cirugía tanto en dos pacientes con feocromocitomas bioquímicamente no funcionantes como en una paciente con un carcinoma adrenocortical primitivo, este diagnóstico también sugerido por un patrón mixto de hipersecreción de andrógenos y cortisol. En una paciente con síndrome de Cushing subclínico, hipertensa y diabética, ambas comorbilidades fueron resueltas por la cirugía. Los tumores no funcionantes fueron en su mayoría adenomas (87%), hallándose además histoplasmosis, pseudoquiste, hiperplasia suprarrenal idiopática y mielolipoma. Seis de los ocho pacientes operados tenían enfermedad maligna y/o hiperfuncionante. La condición asociada a los incidentalomas suprarrenales significó un amplio espectro de riesgo para los pacientes y reafirma la necesidad de una minuciosa evaluación clínica, bioquímica y de las imágenes a fin de adoptar conductas adecuadas.(AU)

Adrenal incidentaloma, a tumor discovered unexpectedly during imaging performed for non-adrenal related causes, has become a frequent clinical concern. Although in most cases they are benign and hormonally nonfunctioning, it is important to appropriately identify those few cases of malignant or hyperfunctioning lesions of surgical resolution. Although several proposals for an optimal diagnostic strategy have been designed, controversy over a series of questions still persists. In the present retrospective study we analyzed 34 patients with adrenal incidentaloma. Of these, 32% of the patients displayed hyperfunctioning pathologies that included subclinical Cushings syndrome in four patients, probable primary hyperaldosteronism in two, late onset congenital adrenal hyperplasia in one, adrenocortical carcinoma in one and pheochromocytoma in three. CT and/or MRI permitted the identification of adenomas and were crucial to decide on surgery in two patients with nonfunctioning pheochromocytomas and in a patient carrying a primitive adrenocortical carcinoma, a diagnosis also suggested by a mixed pattern of hypersecretion of androgens and cortisol. In a diabetic and hypertensive patient with subclinical Cushings syndrome both comorbidities were solved by surgery. Nonfunctioning tumors were mainly adenomas (87%) with individual cases of histoplasmosis, pseudocyst, idiopathic adrenal hyperplasia and mielolipoma. Six of the eight operated patients presented malignant and/or hyperfunctioning tumors. The pathology associated with incidentalomas represents a broad spectrum of risk for patients and reaffirms the necessity for a meticulous clinical, biochemical, and imaging evaluation in order to make appropriate decisions.(AU)

Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushings syndrome

El síndrome de Cushing (SC) es un trastorno grave que requiere frecuentemente tratamiento medicamentoso. Cincuenta y cuatro pacientes (44 mujeres, 10 varones) de 14-63 años de edad con SC, recibieron ketoconazol (KTZ) previo a cirugía (n=27), como complemento luego de cirugía y/o radioterapia (n=16), o como tratamiento primario (n=11). La dosis de mantenimiento fue de 600 (500 - 600) mg/día (mediana-IC95) durante 15 días a 13 años. Los signos clínicos, hepatograma y cortisol libre urinario (CLU) fueron evaluados antes y durante tratamiento con KNZ. El CLU cayó a valores normales o subnormales en 85% de los pacientes, 5 a 150 días luego de iniciar el tratamiento; aún sin normalizar, el CLU disminuyó a 12-48% de los valores pre-tratamiento en el resto de los pacientes acompañándose de mejoría de los signos clínicos. Los efectos colaterales fueron: insuficiencia adrenal (18.5%), toxicidad hepática reversible (11%), "rash" cutáneo (5.5%) e intolerancia gástrica (3.7%); en 11% de los pacientes se observó un fenómeno de "escape". Veinticuatro pacientes (44.4%) fueron tratados por períodos prolongados, de uno a trece años. Este estudio confirma que el KTZ constituye un tratamiento eficaz y generalmente bien tolerado del SC, en particular: a) como preparación para cirugía b) en casos de hipercortisolismo residual luego de cirugía o en espera de resultados de radioterapia, c) como una alternativa razonable en pacientes con SC de origen desconocido y, d) como tratamiento crónico en casos de hipercortisolismo no resuelto luego de fracaso de las terapéuticas habituales.(AU)

Cushings syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - CI95) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.(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. (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)

Experiencia clinica sobre 37 casos de insulinoma / Clinical experience in 37 cases of insulinoma

El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años) y 14 varones (45 ± 19 años) con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnósticofue de 2.8 ± 2.1 años. Veintisiete pacientes (73%) presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA) 38.2 ± 39.7 μU/ml (n=11), insulina (quimioluminiscencia) 23.8 ± 18.1 μU/ml (n=26), péptido C1.15 ± 1.6 nmol/l (n=14). El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21). La localizaciónpreoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnósticofue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1%) presentaron insulinomas únicos(16 en cuerpo y cola, 6 en la cabeza y proceso uncinado), 6 eran portadores de insulinomas múltiples, 5 deinsulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1). Una paciente no fue operada recibiendotratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses (AU)

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis isestablished through demonstration of inappropriately elevated insulin serum concentrations in the presence ofhypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988,23 women (48 ± 18 years) and 14 men (45 ± 19 years) were studied. Seventy three percent of them sufferedmainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms beforediagnosis was 2.7 ± 2 years. Mean fasting serum glucose was 32.4 ± 8.7 mg/dl, insulin 38.2 ± 39.7 μU/ml(RIA, n= 11) or 23.8 ± 18.1 μU/ml (chemoluminescence, n=26) and C-peptide 1.15 ± 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 ± 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour(glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinicalresponse. Mean postoperative follow up was 60.4 ± 59.9 months (AU)

Experiencia clinica sobre 37 casos de insulinoma / Clinical experience in 37 cases of insulinoma

El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años) y 14 varones (45 ± 19 años) con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnósticofue de 2.8 ± 2.1 años. Veintisiete pacientes (73%) presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA) 38.2 ± 39.7 μU/ml (n=11), insulina (quimioluminiscencia) 23.8 ± 18.1 μU/ml (n=26), péptido C1.15 ± 1.6 nmol/l (n=14). El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21). La localizaciónpreoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnósticofue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1%) presentaron insulinomas únicos(16 en cuerpo y cola, 6 en la cabeza y proceso uncinado), 6 eran portadores de insulinomas múltiples, 5 deinsulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1). Una paciente no fue operada recibiendotratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses (AU)

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis isestablished through demonstration of inappropriately elevated insulin serum concentrations in the presence ofhypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988,23 women (48 ± 18 years) and 14 men (45 ± 19 years) were studied. Seventy three percent of them sufferedmainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms beforediagnosis was 2.7 ± 2 years. Mean fasting serum glucose was 32.4 ± 8.7 mg/dl, insulin 38.2 ± 39.7 μU/ml(RIA, n= 11) or 23.8 ± 18.1 μU/ml (chemoluminescence, n=26) and C-peptide 1.15 ± 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 ± 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour(glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinicalresponse. Mean postoperative follow up was 60.4 ± 59.9 months (AU)

Embarazo luego de necrosis espontanea de un macroadenoma pituitiario / Pregnancy after spontaneous necrosis of a pituitary macroadenoma

Although infrequent, recovery of pituitary function after necrosis of a pituitary adenoma is not an exceptional event. We report the case of a 32-year-old woman with previous surgery for an adrenal mass and signs of hypercortisolism which failed to revert postoperatively. She then developed pituitary apoplexy followed by hypopituitarism, as confirmed by hormonal measurements. Magnetic resonance imaging (MRI) showed evidence of a pituitary macroadenoma with signs of necrosis, impinging on the optic chiasm, which was excised by the trans-sphenoidal approach. Nine months later, hormone tests indicated a near total recovery of pituitary functions. The patient had a successful pregnancy three years later. After a 5-year follow-up, she remained clinically asymptomatic, with moderate reduction in cortisol and blunted growth hormone (GH) response to hypoglycemia and MRI failed to disclose any residual tumor, except for a partial arachnoidocele (AU)

Medición de cortisol y sus fracciones. Una puesta al día. / [A critical analysis of cortisol measurements: an update].

Serum cortisol measurement is a very useful tool in the biochemical evaluation of adrenocortical function. Since this hormone circulates in blood mainly linked to binding globulins but is also partially free, it can be measured not only in the blood but also in urine, saliva and other biological fluids and tissues. Basal determinations as well as dynamic testing may be performed to evaluate the circadian variations, to estimate the diurnal cortisol secretion and to analyze its relations with other components of the hypothalamic-pituitary-adrenal axis. Measurements of cortisol in blood, saliva and urine may reflect the cortisol secretion at the time of sample collection or during a 24 h span. Recently, it has been proposed the determination of cortisol in tissues such as hair and nails like a means of evaluating the hormonal status during prolonged periods. The aim of this paper is to update the methodology for measuring cortisol and its usefulness for the clinical diagnosis of troubles of the hypothalamic-pituitary-adrenal axis.

Tiroiditis no-autoinmunes. / [Non-autoimmune thyroiditis].

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Pseudo-tumor pituitario e hipopituitarismo secundario a un papiloma invertido del seno esfenoidal. / [Pseudo-pituitary tumor and hypopituitarism secondary to a sphenoid sinus inverted papilloma].

Inverted papilloma (IP) is a benign uncommon epithelial tumor, arising mostly from the lateral nasal wall. Though benign, this lesion is highly invasive into surrounding tissues and malignant transformation may occur. Primary IP of the sphenoid sinus and intracranial extension with dural invasion, even without histological evidence of malignancy, has only rarely been described. Hypopituitarism as a complication of this lesion has never been reported. We describe the case of a 59-year-old woman who was evaluated because of a 5-year-history of severe headaches and abnormalities in the visual field. Magnetic resonance imaging (MRI) showed a 1.4 per 2.0 cm heterogeneous sellar lesion with suprasellar and sphenoid sinus extension, eroding the sellar floor with optic chiasm compression. Otolaryngologists gave her 16 mg/day of prednisone during approximately 3 months with a near total regression of the mass on MRI. The endocrine biochemical evaluation showed pituitary gonadal, thyroid and adrenal insufficiency. A new MRI showed growth of the tumor with obliteration of the sphenoid sinus. An endoscopic sinus biopsy revealed an IP, so a transnasal endoscopic sinus surgery was performed with complete resection evidenced by MRI a year later.

Absence of mutations in the P53 tumor suppressor gene in non-invasive Cushing adenomas

A lot of evidence supports the existence of a monoclonal origin for pituitary tumors, and several genetic alterations have already been confirmed as necessary or sufficient for unrestrained cellular growth and pituitary function. The p53 gene, a known tumor-suppressor gene (TSG), encodes a protein that exerts antiproliferative effects such as cell-growth arrest and apoptosis in response to several types of stimuli. In fact, several human cancers are believed to be caused by p53 mutations. In the case of pituitary tumors, p53 protein accumulation has been described in ACTH-secreting pituitary adenomas. Since increased amounts of the p53 protein are often related to mutations of its gene, we decided to explore the existence of p53 mutations in the tumor tissues of 9 patients bearing non-invasive corticotropinomas, excised by the transphenoidal route. We screened mutations in exons 5 to 8 of the p53 gene by the PCR-SSCP analysis. We were not able to find any mutation in the exons investigated. Our results are in close accordance with those obtained previously for other types of pituitary tumors. (AU)

Supresion nocturna con alta dosis de dexametasona y test de metopirona en el diagnostico etiologico del sindrome de Cushing / Night supression with high doses of dexamethasone and metyrapone tests for the etiological diagnosis of Cushing syndrome

El síndrome de Cushing (SC) es un trastorno grave aunque curable para el que se han propuesto diferentes estrategias de diagnóstico etiopatogénico. Entre ellas, los tests que exploran la regulación de la secreción de cortisol son de gran utilidad aunque no existe homogeneidad de criterios respecto a la elección de los mismos. En este estudio se investigaron 61 pacientes de 13-61 años con SC, quienes fueron classificados según hallazgos quirúrgicos, patológicos y evolución post-tratamiento, en: de origen pitutario 41, por tumor adrenal 16 y SC ectópico 4. En la totalidad de los pacientes se realizó una prueba de inhibición de la cortisolemia con una dosis nocturna de 8 mg de dexametasona. En 43 de ellos, se efectuó edemás un test metopirona con medición de 11-desoxicortisol sérico. Ambas pruebas evidenciaron valores elevados de sensibilidad, especificidad, índice de validez y poder predictivo positivo, obteniéndose los porcentajes mayores (97, 100, 98 y 100 por ciento, respectivamente) con su empleo conjunto. El uso combinado de ambos tests constituye un medio simple y con elevados criterios de validez para el diagnóstico etiológico del SC. (AU)

Embarazo luego de necrosis espontánea de un macroadenoma pituitario. / [Pregnancy after spontaneous necrosis of a pituitary macroadenoma]

Although infrequent, recovery of pituitary function after necrosis of a pituitary adenoma is not an exceptional event. We report the case of a 32-year-old woman with previous surgery for an adrenal mass and signs of hypercortisolism which failed to revert postoperatively. She then developed pituitary apoplexy followed by hypopituitarism, as confirmed by hormonal measurements. Magnetic resonance imaging (MRI) showed evidence of a pituitary macroadenoma with signs of necrosis, impinging on the optic chiasm, which was excised by the trans-sphenoidal approach. Nine months later, hormone tests indicated a near total recovery of pituitary functions. The patient had a successful pregnancy three years later. After a 5-year follow-up, she remained clinically asymptomatic, with moderate reduction in cortisol and blunted growth hormone (GH) response to hypoglycemia and MRI failed to disclose any residual tumor, except for a partial arachnoidocele.

Hiperandrogenemia femenina y niveles séricos normales de testosterona y globulina ligadora de esteroides sexuales. / [Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin].

It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i) determine reference ranges for serum testosterone (T) and sex hormone binding globulin (SHBG) appropriate to our laboratory and population, and (ii) to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a) 30 selected non-hyperandrogenic women, (b) 87 non-selected healthy female blood donors, (c) 53 women with hyperandrogenism, and (d) 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a). Using our results for this selected control group as new reference values, 12 out of 38 (31.6

) women with hyperandrogenic disorders without apparent hyperandrogenemia (group d) were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4

) non-selected, normal weight, women (group b), were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.

Diagnostico por imagenes en la enfermedad de Cushing y su correlacion con la evolucion postquirurgica / Image diagnosis in Cushings disease and its correlation with postsurgical evolution

El objetivo de este trabajo es evaluar la sensibilidad (S) de la tomografía computada (TC) y la resonancia magnética nuclear (RMN) para visualizar un adenoma pituitario en pacientes con enfermedad de Cushing (EC) y correlacionar los hallazgos con la evolución postquirúrgica. Se estudiaron en forma retrospectiva los hallazgos por imágenes de 44 pacientes con EC. Se evaluaron 23 TC y 29 RMN obtenidas previamente a la cirugía hipofisiaria. Se los clasificó como curados o no curados según los criterios bioquímicos y clínicos y la evolución postquirúrgica. De las 23 TC, 13 evidenciaron adenoma y 10 fueron negativas, con una S de 56.5 por ciento. Para la RMN la S fue mayor (86.0 por ciento; P: 0.037, con correción de Yates) con 25 imágenes positivas y 4 negativas de las 29 realizadas. De los 44 casos estudiados 31 (70.5 por ciento, IC 0.70 + 0.13) curaron (27 total, 4 parcial): 23 tenían diagnóstico prequirúrgico por TC y/o RMN. Trece pacientes persistieron con EC con bioquímica de hipercortisolismo. En 11 de ellos se había localizado el adenoma antes de la cirugía. El diagnóstico de enfermedad de Cushing fue confirmado por histología en 33 casos, no lográndose evidenciar tejido tumoral en los 11 restantes. La tasa de remisión fue significativamente mayor en el grupo con confirmación anatomo-patológica, 82 por ciento vs 36 por ciento respectivamente (P< 0.0078). En conclusión: 1) la RMN tendría mayor S que la TC para la localización de un adenoma en la enfermedad de Cushing (P: 0.0373, luego de correción de Yates), confirmando los datos de la literatura; 2) no se halló correlación entre ausencia de imagen y falta de curación; 3) la tasa de remisión es significativamente mayor en los casos con verificación histológica del adenoma pituitario. (AU)