ABSTRACT Objective We analyzed the clinical, biochemical, and imaging findings of adrenalectomized patients with Cushing’s disease (CD) in order to compare the characteristics of those who developed Nelson’s syndrome (NS) versus those who did not develop this complication (NNS), aiming to identify possible predictive factors for its occurrence. Subjects and methods We performed a retrospective review of the clinical records of a group of patients with CD who underwent TBA between 1974 and 2011. Results Out of 179 patients with CD, 13 (7.3%) underwent TBA. NS occurred in 6 of them (46%) after a mean of 24 months from the total bilateral adrenalectomy (TBA). Age at diagnosis, duration of Cushing’s syndrome (CS) until TBA, and steroid replacement doses were similar in both groups. Initial urinary cortisol levels (24-hour urinary free cortisol [UFC]) were significantly higher in the NS group than in the NNS group (p = 0.009). Four patients in the NS group and three of those in the NNS group received radiotherapy before TBA (p = 0.26). Three patients in the NS group presented residual tumors before TBA, compared with none in the NNS group (p = 0.04). At 1 year after TBA, the median ACTH level was 476 ng/L (240-1500 ng/L) in the NS group and 81 ng/L (48-330 ng/L) in the NNS group (p = 0.0007). Conclusion In conclusion, a residual tumor before TBA, higher 24-hour UFC at diagnosis, and increasing ACTH levels within 1 year after TBA emerged as predictive factors of development of NS.

Distant metastases occur in less than 10% of patients with differentiated thyroid carcinoma. In these patients, overall survival at 10 years is considerably reduced. Whereas cure is the initial goal of treatment, stabilisation of the disease and management of symptoms have become the primary objective in many patients with persistent radio-iodine refractory progressive disease. In the last decade, several targeted therapies have shown encouraging results in patients with advanced disease. The objective of this review is to describe the characteristics, diagnosis, overall survival, and the local and systemic available treatments for patients with distant metastases from differentiated thyroid cancer.

La presencia de metástasis a distancia en el cáncer diferenciado de tiroides es un hecho infrecuente que ocurre en menos del 10% de los pacientes. Cuando sucede, la supervivencia a 10 años disminuye significativamente. La curación es el objetivo primario, pero dado que 2 tercios de los tumores metastásicos se volverán radiorrefractarios en su evolución, la finalidad terapéutica es estabilizar la enfermedad y tratar sus síntomas. En la última década, el manejo de estos pacientes cambió radicalmente con el advenimiento de las terapias con blancos moleculares. El objetivo de esta revisión es describir las características de los pacientes con cáncer diferenciado de tiroides que presenten metástasis a distancia, la supervivencia global, los métodos diagnósticos utilizados, y los tratamientos locales y sistémicos disponibles.

Craniopharyngioma is the most common pituitary tumor in childhood. It can compromise the pubertal development because of its evolution or treatment. Syndrome of Klinefelter is the most common cause of hipergonadotrophic hypogonadism in males. The concomitant presentation of both entities is extremely low (1/10(9)) and the pathophysiological association is questionned. We present the case of a 18-year-old Belgian patient. He had a diagnosis of craniopharyngioma in childhood and he presented with panhypopituitarism after radiotherapy and surgical treatment. At the age of 14, he started pubertal induction with gonadotropin therapy without clinical response. A genetic evaluation confirmed a homogeneous 47, XXY karyotype. Failure of exogenous gonadotropin therapy revealed the hidden association of primary and secondary hypogonadism, demonstrating the importance of the followup and a multidisciplinary approach in these patients.

Los craneofaringiomas son de los tumores hipofisarios más frecuentes en la niñez y, sea por su evolución o por el tratamiento que requieren, pueden comprometer el desarrollo puberal. El síndrome de Klinefelter es la causa más frecuente de hipogonadismo hipergonadotrópico en el varón. La presentación concomitante de ambas entidades es extremadamente baja (1/10(9)) y plantea un interrogante acerca de una probable asociación fisiopatológica. Se presenta el caso de un paciente belga de 18 años, con diagnóstico de craneofaringioma en la niñez y panhipopituitarismo luego del tratamiento quirúrgico y radioterápico. Al llegar a los 14 años, se inició la inducción puberal con gonadotropinas. Ante la falta de respuesta clínica, se completó una evaluación genética, que evidenció, de manera homogénea, una trisomía XXY. La falta de respuesta al tratamiento de inducción con gonadotropina exógena reveló la asociación de hipogonadismo primario y secundario, que demostró la importancia del seguimiento multidisciplinario que estos pacientes requieren.

The prevalence of palpable thyroid morphological abnormalities does not exceed 8% in the adult population. A free program was conducted in the Hospital de Clínicas (University of Buenos Aires) for the detection of thyroid diseases, inviting subjects who were unaware of a history of these diseases. The aim was to establish the frequency of goitre in the selected population, as well as to evaluate the prevalence of functional disorders and thyroid autoimmunity, and to compare these results with the findings of a similar study performed in 2001¹. The subjects were divided into three groups: Group 1 (n = 186) patients with a history of previously known thyroid disorders (excluded subjects); Group 2 (n = 184) subjects with a family history of thyroid disease, other autoimmune diseases, or symptoms that could be attributed to changes in thyroid function (Induced Group), and Group 3 (n = 288) subjects who participated in this program due to mere curiosity (Random Group). Autoimmunity and thyroid function was assessed in 144 randomly selected participants in Group 3. In Group 3, the prevalence of morphological alterations of the thyroid gland was 11.09%. Comparing these results with those obtained 12 years ago in a similar study performed in our hospital, no statistically significant differences were found when the prevalence of morphological thyroid alterations were compared (8.7% vs 11.09%, p=.25). As for thyroid function, subclinical hypothyroidism was found in 6.25%, subclinical hyperthyroidism in 0.7%, and autoimmunity in 11% of subjects evaluated. It was concluded that the prevalence of palpable thyroid abnormalities had not change in the last decade. This study, made in a correctly selected population, is a useful tool for future reference as a control population in Argentina.

La prevalencia de alteraciones morfológicas palpables tiroideas no supera el 8% en la población adulta. En el Hospital de Clínicas de la Universidad de Buenos Aires se llevó a cabo un programa gratuito para la detección de enfermedades tiroideas, convocándose a sujetos que desconocieran antecedentes tiroideos. Nuestro objetivo fue establecer la frecuencia de patología morfológica palpable tiroidea, en una población seleccionada de pacientes, y comparar dichos resultados con los hallazgos de un programa de detección similar, realizado en el año 2001¹. Adicionalmente, evaluar la prevalencia de alteraciones funcionales y de autoinmunidad tiroidea. Los individuos que concurrieron se dividieron en 3 grupos: Grupo 1 (n = 186) pacientes con antecedentes personales de enfermedad tiroidea conocida (excluidos del análisis); Grupo 2 (n = 184) sujetos con antecedentes familiares, otras enfermedades autoinmunes, o sintomatología que pudiera atribuirse a alteración de la función tiroidea (grupo inducido), y Grupo 3 (n = 288) sujetos que consultaron por mera curiosidad (grupo random). La función y autoinmunidad tiroidea se evaluó en 144 participantes del Grupo 3, citados al azar. En el grupo random, la prevalencia de alteraciones morfológicas tiroideas, detectadas por palpación, fue del 11,09%. Al comparar estos resultados con los obtenidos 12 años atrás en un estudio similar, realizado en nuestro hospital, no se encontraron diferencias estadísticamente significativas (8,7 vs. 11,09%; p = 0,25). En cuanto a la función tiroidea, se halló hipotiroidismo subclínico en el 6,25%, hipertiroidismo subclínico en el 0,7% y autoinmunidad en el 11% de los sujetos evaluados. En conclusión, la prevalencia de alteraciones palpables de la glándula tiroides no cambió en laúltima década. Esta investigación realizada en una población correctamente seleccionada constituye una herramienta útil para referencias futuras como población control en Argentina.

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

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.

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.

Patients infected with human immunodeficiency virus (HIV) have a higher prevalence of thyroid dysfunction when compared with the general population. The most frequently observed manifestations are euthyroid sick syndrome, Graves´ disease and subclinical hypothyroidism. The relationship between the use of highly active antiretroviral therapy and the increased prevalence of thyroid dysfunction has been demonstrated in several series of patients. Grave’s disease is recognized as a consequence of immune restitution syndrome. Besides, several studies have suggested an association between hypothyroidism and the use of nucleoside reverse transcriptase inhibitors, particularly stavudine and non-nucleoside reverse transcriptase inhibitors such as efavirenz. Further studies could provide additional evidence of the need for routine assessment of thyroid function in HIV-infected patients.

Los pacientes con infección por el virus de inmunodeficiencia humana (HIV) tienen una mayor prevalencia de disfunción tiroidea cuando se los compara con la población general. Las manifestaciones más frecuentemente observadas son: el síndrome del eutiroideo enfermo, la enfermedad de Graves y el hipotiroidismo subclínico. La relación entre el uso de la terapia antirretroviral y el incremento en la prevalencia de alteraciones tiroideas fue demostrada en varias series de pacientes. La enfermedad de Graves se reconoce claramente como una consecuencia del síndrome de restitución inmune. Además, existen estudios que sugieren una relación entre hipotiroidismo y el uso de inhibidores nucleósidos de la transcriptasa reversa, en particular estavudina y el inhibidor no nucleósido de la transcriptasa reversa efavirenz. Nuevos estudios podrán aportar evidencia adicional sobre la necesidad de evaluaciones rutinarias de la función tiroidea en pacientes infectados por HIV.

OBJETIVO: O objetivo deste estudo foi determinar se o câncer de tiroide não medular (CNMF) é mais agressivo do que o câncer esporádico de tiroide. SUJEITOS E MÉTODOS: Comparamos o comportamento clínico e a evolução de 16 portadores de CNMF de sete famílias não relacionadas com 160 CP (câncer papilífero) esporádicos de nosso serviço. RESULTADOS: As únicas diferenças nas características basais dos grupos eram: malignidade bilateral 38% vs. 24%, respectivamente (p = 0,03), e metástases linfonodais, 57,1% vs. 39%, respectivamente (p = 0,01). Em relação à evolução, 9 (56,2%) pacientes com CNMF ficaram livres de doença, um paciente faleceu devido ao CP (6%) e 6/16 (37,5%) apresentavam persistência da doença. No grupo de CP esporádicos, 87 (54%) foram considerados livres de doença, 11 (7%) morreram em decorrência do CP e 62 (38%) apresentavam persistência da doença (p = ns). CONCLUSÃO: Apesar da elevada incidência de metástases linfonodais nos pacientes com CNMF, essa situação não parece alterar a evolução dos dois grupos em longo prazo.

OBJECTIVE:The purpose of this study was to determine whether familial non-medullary thyroid cancer (FNMTC) is more aggressive than sporadic thyroid cancer. SUBJECTS AND METHODS: We compared the clinical behavior and outcome of 16 subjects with FNMTC from 7 unrelated kindred with those observed in 160 subjects with sporadic PTC (SPTC) from our database. RESULTS: The only different baseline characteristics observed between both groups were: bilateral malignancy, 38% vs. 24%, respectively (p = 0.03), and lymph node metastasis, 56.2% vs. 39%, respectively (p = 0.01). Considering the outcome, in the FNMTC, 9 (56.2%) patients were rendered free of disease, one patient died from thyroid cancer (6%), and 6/16 (37.5%) had persistent disease. In the SPTC Group, 87 (54%) patients were considered free of disease, 11 (7%) died due to PTC, and 62 (38%) had persistent disease (p = ns). CONCLUSIONS: Despite the higher incidence of lymph node metastasis in FNMTC patients this situation seemed not to alter the compared outcome.

In the familial form of papillary thyroid cancer (PTC), two or more members of the same family have to be affected with PTC. Prevalence is around 5% of all PTC. We performed a clinical analysis in 79 relatives of 16 patients of 7 unrelated kindred with the diagnosis of familial papillary thyroid carcinoma (FPTC). The results were compared with a control group. Thyroid palpation and TSH and TPO-Ab assessment was carried out in the relatives without a diagnosed PTC. Additionally, molecular analysis was performed in the sixteen affected patients. Clinical screening of the 79 family members showed the presence of goiter in 22/79 (29 %). This frequency was much higher than that observed in the control group (8.7%), p < 0.001. Hypothyroidism was found in 4 of the relatives (5%) vs. 2.5% observed in the control group, p < 0.01, and anti-thyroid antibodies (TPO-Ab) were positive in 14% of the relative's group vs. 10 % in the control group, (p = NS). In the molecular analysis, only a protooncogene TRK rearrangement was observed in family # 6. In conclusion, we found a higher incidence of goiter and hypothyroidism in the relatives of patients with FPTC. Nevertheless, TPO-Ab frequency was not different. No molecular abnormalities were indicative of a specific pattern in this subset of patients with FPTC.

En la forma familiar del carcinoma papilar de tiroides (CPT), dos o más miembros de la misma familia deben presentar CPT. Esta entidad ocurre en aproximadamente el 5% de todos los CPT. En este estudio, realizamos una evaluación de 79 familiares de 16 pacientes con diagnóstico de carcinoma papilar familiar (CPF) provenientes de 7 familias diferentes. Los resultados se compararon con los hallados en un grupo control. Se realizó palpación tiroidea y medición de TSH y anticuerpos anti-tiroperoxidasa (TPO-Ab) en todos los familiares. Además, se llevó a cabo el análisis molecular en los 16 sujetos que presentaban el diagnóstico de CPF. La evaluación de los 79 familiares de estos pacientes demostró la presencia de bocio en 22/79 (29%). Esta frecuencia fue mucho mayor que la observada en el grupo control (8.7%), p < 0.001. Se diagnosticó hipotirodismo en 4 familiares (5%) vs. 2.5%, observado en el grupo control, p < 0.01, y los TPO-Ab fueron positivos en 14% de los familiares vs. 10% del grupo control, (p = ns). En el análisis molecular, solamente se halló un rearreglo del protoncogen TRK en una de las 7 familias con CPF. En conclusión, hallamos una elevada prevalencia de bocio e hipotiroidismo en los familiares de pacientes con CPT. Sin embargo, la frecuencia de autoinmunidad no fue diferente. No se hallaron alteraciones moleculares distintivas en estos pacientes con CPF.

Paciente de 29 anos foi encaminhada ao Hospital de Clínicas por causa de convulsões generalizadas. Apresentava hipertiroidismo tratado com metimazol (MMI). A ressonância magnética mostrava quatro lesões metastáticas cerebrais. Possuía bócio com nódulo frio e linfonodo palpável ipsilateral. Usando 5 mg de MMI, a paciente apresentava hipertiroidismo subclínico e TRAb = 47,8% (normal < 10%). A tomografia computadorizada também mostrava metástases pulmonares. A paciente foi submetida a tiroidectomia total com dissecção cervical modificada e recebeu dose acumulada de radioiodo de 700 mCi durante o período de dois anos. Foi analisado o DNA extraído de tecido emblocado em parafina do tumor, do linfonodo metastático e de tecido tiroidiano não-tumoral. Foram encontradas mutações pontuais em dois genes: uma substituição do genótipo selvagem CAA no códon 61 de /N-RAS/ por CAT, substituindo a glicina pela histidina (G61H) e uma substituição da seqüência normal GCC no códon 623 do gene TSHR por TCC, trocando a alanina pela serina (A623S). Não foram encontradas mutações no tecido não-tumoral. Estudos in vitro mostraram ativação constitutiva de TSHR. Já que esta mutação ativadora de TSHR foi incapaz de atingir o final da cascata PKA no tecido tumoral, sugere-se que um mecanismo de cross-signaling possa explicar o desvio da cascata do receptor de TSH para outra mais proliferativa, envolvendo MAPKinase e levando ao comportamento mais agressivo deste câncer papilífero.

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

We investigated 252 non-obese female subjects aged 13-39 years to evaluate if an exaggerated descent of sex hormone binding globulin (SHBG) levels during adolescence can play a role in the development of hirsutism. Body hair was assessed according to Ferriman and Gallwey (FG), with a stringent criterion of normality of < 4. In 13-14 years girls, SHBG and free testosterone (FT) levels were similar in "hirsute" girls (FG > 4) and controls (FG < 4, regular menstrual cycles, no acne). In 15-18 years girls, SHBG values were lower in "hirsute" girls, FT levels were similar in both groups, FG correlated inversely with SHBG. In 19-39 yr women, FT levels were higher in "hirsute" subjects, SHBG values were similar in both groups, FG correlated positively with FT. Lowest SHBG values were observed at 15-18 years, but the slope of the decrease from 1314 years values was greater in the "hirsute" group. FT values increased progressively with age, but the increase was greater in the "hirsute" group. Those results suggest an important role of SHBG decrease in adolescence vs. a more accentuated testosterone increase in adults, as factors conditioning the development of hirsutism in these two different periods of life.

Se investigaron 252 mujeres con peso normal, de 13 a 39 años de edad, para evaluar si un descenso exagerado en los niveles de la globulina transportadora de hormonas sexuales ("sex hormone binding globulin"; SHBG) puede tener un rol en el desarrollo de hirsutismo. Este signo fue evaluado con la escala de Ferriman y Gallwey (FG), empleando un criterio riguroso de normalidad < 4. En niñas de 13-14 años, tanto SHBG como la testosterona libre ("free testosterone"; FT) fueron similares en niñas "hirsutas" (FG > 4) y controles (FG < 4, ciclos menstruales regulares, sin acné). En adolescentes de 15-18 años, los valores de SHBG fueron menores en las "hirsutas", los niveles de FT fueron similares en ambos grupos y el índice de FG correlacionó inversamente con SHBG. En las mujeres de 19-39 años, los niveles de FT fueron mayores en las "hirsutas", los valores de SHBG fueron similares en ambos grupos y FG correlacionó positivamente con FT. Los valores más bajos de SHBG se observaron entre 15 y 18 años, pero la pendiente de disminución a partir de los valores de 13-14 años fue mayor en el grupo de "hirsutas". Los valores de FT se incrementaron progresivamente con la edad, pero el aumento fue mayor en el grupo de "hirsutas". Estos resultados sugieren un rol importante del descenso de SHBG en la adolescencia vs. un incremento más acentuado de los niveles de testosterona en las adultas, como factores que condicionan el desarrollo del hirsutismo en esos dos diferentes periodos de la vida.

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 more marked 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 re-evaluated 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.

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.