Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Pituitary gigantism: a case series from Hospital de San José (Bogotá, Colombia)

ABSTRACT Introduction Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. Materials and methods Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. Results All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. Conclusions This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.

Adenomas hipofisarios en pacientes añosos / Pituitary adenomas in elderly patients

Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospectivo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.

Pituitary adenomas in elderly patients

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenomas. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57%, respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenomas and normal visual field were periodically controlled, and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.1 months). We did not observe tumor progression in elderly patients with non-functioning adenomas and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.

Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospecti vo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.

A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors’ experience. Arch Endocrinol Metab. 2016;60(4):374-90.

Paresia del III par craneal como manifestación de un corticotropinoma silente / Third nerve palsy as an expression of a corticotroph adenoma

Silent corticotroph adenomas (SCA) are pituitary adenomas inmunoreactive to ACTH without hormonal overproduction and they form the 3 percent of the pituitary adenomas. Unlike the ademonas that cause the Cushing’s disease, frequently the SCA are aggressive macroademonas and their clinical expressions are the compromise of nearby structures with or without pituitary apoplexy. Frequently, the treatment chosen is a surgical procedure, albeit the total resection difficulties. The SCA are not diagnosed until an anatomopathological and immunohistochemical study is carried out. In this document, a case study of a woman diagnosed with a clinically silent macrocorticotroph adenomadiscovered by a third nerve palsy is explained.

Análisis de un registro de adenomas pituitarios / Analysis of a pituitary adenoma registry

Dada la complejidad que reviste el enfoque diagnóstico y terapéutico de los tumores pituitarios, el registro y análisis de la experiencia clínica acumulada es de gran ayuda en la toma de decisiones. En este trabajo se informan datos clínico-terapéuticos, extraídos de un registro computarizado, sobre 519 de un total de 670 pacientes con adenomas pituitarios. Trescientos cuarenta y cinco fueron mujeres (66%) y 174 varones (34%), de 14 a 80 años de edad. El diagnóstico final fue: acromegalia en 176, enfermedad de Cushing en 153, prolactinoma en 101 y adenoma clínicamente no-funcionante (ANF) en 89. La edad media al momento del diagnóstico de acromegalia fue 43.9 ± 13.5 (16-80), para enfermedad de Cushing 35.7 ± 12.9 (14-72), para prolactinomas 30.0 ± 13.4 (15-79) y para ANF 52.1 ± 15.2 (17-79) años. La creación de un registro institucional de tumores de hipófisis es un instrumento de gran utilidad para el análisis de la experiencia adquirida y constituye una herramienta valiosa para mejorar la estrategia terapéutica, optimizar la relación costo/beneficio y mejorar el cuidado del paciente. Contribuye a la docencia médica, tanto en el pre como en el posgrado y da base a la realización de trabajos de investigación clínica, aportando a la difusión y transferencia de conocimientos.

Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations. We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry. Three hundred and forty five were females (66%) and 174 males (34%), aged 14-80. Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89. Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours. The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care. It greatly contributes to teaching medical students as well as to post-graduate physicians and provides a basis for developing clinical research.

Hiponatremia sintomática como forma de presentación clínica de un macroadenoma hipofisiario: Comunicación de tres casos / Hyponatremia associated to pituitary adenomas: Report of three patients

Severe hyponatremia occurring as the presenting feature of hypopituitarism secondary to pituitary adenomas is rare. We report three patients with this condition: Two elderly males (74 and 78 year-old) presenting with impaired consciousness and low plasma sodium after an episode of diarrhea and a 56-year-old male presenting with impaired consciousness after an episode of vomiting. All had clinical features of hypopituitarism and pituitary adenomas were found on imaging studies. Two were subjected to a trans sphenoidal resection of the adenoma.

El incidentaloma hipofisario / Hypophyseal incidentalomas

El rápido desarrollo y la gran precisión en las técnicas de imagen han fomentado el hallazgo incidental de lesiones asintomáticas de la hipófisis que imponen un reto de manejo tanto para el clínico como para el neurocirujano. Estas masas llamadas incidentalomas se encuentran en cerca de 10% de las resonancias magnéticas realizadas en individuos sanos. Hasta ahora no se conoce con exactitud la historia natural de estas lesiones. Algunas no se modifican con el tiempo, e incluso disminuyen espontáneamente de tamaño, mientras que otras tienen el riesgo de aumentar de volumen y producir síntomas por efectos de masa o hipersecreción hormonal. Esta revisión pretende dar a conocer el consenso actual en cuanto a las estrategias diagnósticas y terapéuticas en el paciente con incidentaloma hipofisario. Se hace énfasis en los factores, ya sea clínicos, bioquímico-hormonales o imagenológicos, que por sí mismos sugieren un alto riesgo de crecimiento tumoral.

The rapid development of highly accurate imaging techniques, has led to the discovery of asymptomatic lesions within the pituitary gland that constitute a significant challenge for clinicians and neurosurgeons. These lesions found incidentally are termed incidentalomas and can be observed in approximately 10% of MRI studies performed among healthy subjects. The natural course of these lesions has not been clearly defined. Although some of these masses do not change in size overtime and some may even shrink spontaneously, others have the potential risk to increase in volume and cause symptoms associated with mass effect or hormonal hypersecretion. This review describes the current therapeutic and diagnostic consensus in incidentaloma management, and places special emphasis on hormonal and imaging factors suggestive of high risk tumors.

Silent corticotroph adenomas

Silent corticotroph pituitary adenomas (SCA) are defined as pituitary adenomas showing positive staining for adrenocorticotrophic hormone in immunohistochemical studies, but not associated with perioperative clinical or laboratory features of hypercortisolaemia. They account for 1.1-6 percent of surgically removed pituitary adenomas. Currently, two distinct pathologic subtypes of SCA are recognised. Their pathogenesis remains unclear. They present with local mass effects (headache, visual deterioration, cranial nerve palsies, endocrine dysfunction). The lack of manifestations of cortisol excess has not been conclusively explained. In surgical series, most tumours are macroadenomas with suprasellar extension present in 87-100 percent of the cases; this is in contrast to Cushing's disease, which is mostly attributed to microadenomas. Surgery remains the main therapeutic approach. Attempts to identify predictors of recurrence have not been successful. Management and follow-up protocols should be planned taking into account their potential aggressive behaviour, particularly upon recurrence. The development of florid pituitary Cushing's syndrome and local recurrence followed by metastatic disease (occasionally outside the central nervous system) have been rarely reported.

Adenomas corticotróficos silenciosos (ACS) são definidos como adenomas hipofisários que apresentam coloração positiva para o hormônio adrenocorticotrófico em estudos imuno-histoquímicos, mas não são associados com achados clínicos ou laboratoriais peri-operatórios de hipercortisolemia. São responsáveis por 1,1-6 por cento dos adenomas hipofisários removidos cirurgicamente. Atualmente, dois subtipos patológicos distintos de ACS são reconhecidos, mas sua patogênese permanece obscura. Eles se apresentam com efeitos de massa local (cefaléia, deterioração visual, paralisia de nervos cranianos, disfunção endócrina). A ausência de manifestações de excesso de cortisol não é suficientemente explicada. Em séries cirúrgicas, a maioria dos tumores são macroadenomas com extensão suprasselar, presente em 87-100 por cento dos casos, em contraste com a doença de Cushing, que é principalmente atribuída a microadenomas. A cirurgia continua a principal ação terapêutica. A tentativa de se identificar preditores de recorrência tem sido mal sucedida. Protocolos de manejo e acompanhamento devem ser planejados levando-se em consideração o seu comportamento potencialmente agressivo, particularmente na recorrência. Raramente tem sido reportado o desenvolvimento de síndrome de Cushing hipofisária florida e recorrência local, seguida de doença metastática (ocasionalmente fora do sistema nervoso central).

Adenomas hipofisários produtores de glicoproteínas: patogênese, diagnóstico e tratamento / Glycoprotein-secreting pituitary adenomas: pathogenesis, diagnosis and treatment

Os adenomas hipofisários produtores de glicoproteínas compreendem duas entidades clínicas e patológicas distintas: os adenomas gonadotróficos e os tirotróficos. Embora possam ser agrupados por produzirem hormônios e/ou sub-unidades que são glicoproteínas, esses tumores se originam em tipos celulares distintos (gonadotrofos e tirotrofos) que são apenas remotamente relacionados. Os gonadotróficos estão entre os adenomas hipofisários mais comuns, correspondendo à grande maioria dos assim chamados adenomas "não-funcionantes", silenciosos ou clinicamente não-secretores, enquanto os tirotróficos são extremamente raros e clinicamente se apresentam com hipertiroidismo por secreção inapropriada de TSH. Nesse artigo, os autores revisam aspectos epidemiológicos, patológicos, patogenéticos, clínicos, diagnósticos e terapêuticos desses adenomas. Uma ênfase maior foi dada à patogênese molecular dos tumores hipofisários em geral, buscando, sempre que possível, contrastar as alterações moleculares encontradas nesses adenomas com outros tipos de adenomas hipofisários. No lado mais prático, a experiência dos autores de mais de duas décadas no diagnóstico e tratamento desses tumores na Unidade de Neuroendocrinologia da Unifesp, foi criteriosamente utilizada para discutir a literatura disponível nesses tópicos.

Avaliaçäo da resposta terapêutica aos análogos da somatostatina em uma linhagem de tumores hipofisários somato-mamotróficos transplantáveis do rato

Foram avaliados os efeitos de um análogo da somatostanina, a octreotida, sobre a secreção hormonal e a proliferação celular de tumores hipofisários do rato, secretores de PRL (SMtTW2) ou GH e PRL (SMtTW10), considerados como modelos experimentais de adenomas mamo-somatotróficos. Os tumores primários foram espontâneos, e transplantados sob a cápsula renal de ratos Wistas-Furth-Ico. Os ratos transplantados com os tumores SMtTW2, secretaram apenas PRL. Os animais transplantados com os tumores SMtTW10 apresentaram, no quarto mês do experimento, níveis de GH e de PRL, superiores a 5000 ug/l e 200 ug/l, respectivamente. Neste período, os ratos receberam uma única injeção subcutânea de Octreotida 100 ug/kg e os níveis plasmáticos de GH e de PRL foram determinados após 60 minutos. Visando avaliar os efeitos do tratamento crônico com octreotida, sobre a secreção hormonal e o crescimento tumoral, os animais foram distribuídos em grupos pareados para a idade, que receberam diferentes regimes de tratamento, por um período de três meses[...] Em conclusão, os tumores mamo-somatotróficos SMtTW10 expressam receptores funcionais, que permitem os efeitos agudos da Octreotida sobre a secreção hormonal. A ausência destes efeitos, na vigência de um tratamento crônico, deve-se provavelmente, a um processo de dessensibilização que poderia ocorrer em qualquer etapa da via de sinalização intra-celular, ou os receptores para a somatostatina expressos nos tumores, não apresentam sensibilidade adequada à octreotida

Tratamento medicamentoso dos tumores hipofisários: parte I: prolactinomas e adenomas secretores de GH / Drug therapy of hypophyseal tumors: part I: prolactinomas and GH secretory adenomas

O recente desenvolvimento de novas drogas, particularmente os análogos da somatostatina (SRIFa), representou um grande processo na terapia dos tumores hipofisários. Os SRIFa mostram-se bastante eficazes na normalizaçäo dos níveis de GH e IGH- 1 em acromegálicos e podem ser uma alternativa para a cirurgia transesfeinodal, mas seu uso como terapia primária da acromegalia fica limitado pelo pequeno efeito dessas drogas na reduçäo das dimensöes do tumor. Os resultados preliminares com os antagonistas do receptor de GH, como o pegvisomant, säo bastante animadores. Tais drogas permitem a normalizaçäo do IGF-1 e melhora clínica em mais de 80 por cento dos casos; entretanto, nao causam reduçäo tumoral. Agonistas dopaminérgicos (DA) represemtam a terapia de escolha para microprolactinonas sintomáticos e macroprolactinomas, permitindo normalizaçäo dos níveis da prolactina e reduçäo do volume do adenoma na maioria dos pacientes . Podem também ser eventualmente eficazes em acromegálicos, sobretudo naqueles com adenomas co-secretores de prolactina e níveis näo muito elevados de GH e IGF-1. Devido a sua maior eficácia e maior tolerabilidade, a carbegolina representa o DA de escolha para o manuseio dos prolactinomas e da acromegalia.

Adrenocortical tumors in children

Childhood adrenocortical tumors (ACT) are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of Sao Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations) and selected genetic syndromes (Beckwith-Wiedemann syndrome) have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing). Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S), which are abnormal in approximately 90 percent of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Effect of post-operative thyroid hormone therapy on the recurrence of benign thyroid nodules. A study in Thai patients.

The efficacy of postoperative thyroid hormone treatment in prevention of recurrent thyroid nodule is still controversial. In order to investigate this effect in Thai patients, a retrospective study was performed on files of 321 post-operative patients with benign thyroid nodules, who were either on thyroid hormone treatment or not after surgery, and were followed-up for at least 1 year. The longest follow-up period was 15 years after surgery. The recurrence of nodules was determined by palpation. It was found that the recurrent rate in patients with adenoma who did not receive post-operative thyroid hormone treatment was 20 per cent (16/82 cases) while there was no recurrence at all (0/25 cases) in the treatment group (p < 0.05). The recurrent rate was 22 per cent (31/141 cases) in patients with nodular goitre who did not receive post-operative thyroid hormone treatment and 7 per cent (5/73 cases) in those with treatment (p < 0.001). In the group of patients without post-operative thyroid hormone treatment, for both the group of patients with adenoma and that with nodular goitres, the recurrence was found to occur as late as more than 10 years after surgery.