Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

Anatomía radiológica del seno esfenoidal: análisis en 120 pacientes intervenidos / Radiologic anatomy of sphenoidal sinus, analysis of 120 surgically intervened patients

Introducción: La patología tumoral hipofisiaria es una consulta frecuente en Neurocirugía. La vía de abordaje a elegir preferentemente es transesfenoidal. Por esto, es de suma importancia conocer la anatomía de los senos paranasales cuando se planifica este abordaje. Materiales y Métodos: Se describe la anatomía radiológica de estudios por Tomografía Computada (TC) y Resonancia Magnética (RM) de 120 pacientes con diagnóstico de adenoma hipofisiario, que se sometieron a cirugía transesfenoidal de hipófisis, prestando especial interés en la morfología de las cavidades paranasales esfenoidales. Resultados: Tipo de neumatización: preselar 25 por ciento y postselar 75 por ciento; Septos: simples 45 por ciento y múltiples 55 por ciento; diámetros promedio: antero-posterior 2,3 cm, transverso: 3,3 cm y vertical: 2,25 cm. Los Senos esfenoidales con neumatización postselar tienen un diámetro anteroposterior significativamente mayor (P < 0,005) que los preselares. Los senos esfenoidales con septo simple tienen un diámetro transverso significativamente mayor (P < 0,007) que los con múltiples septos. El 50 por ciento de los septos siguen una trayectoria paramediana, y el 50 por ciento se desvía hacia una de las arterias carótidas. Conclusión: se confirma la gran variación anatómica del seno esfenoidal siendo independiente del sexo del paciente, además hemos constatado que la relación establecida por los septos intraselares con elementos vasculares intracraneales es muy variable, siendo este hallazgo de suma importancia en la planificación preoperatoria. Los hallazgos realizados por Tomografía computada (TC), pueden ser homologables a lo descrito por otros autores en disecciones cadavéricas.

Introduction: The pituitary tumor pathology is a common query in Neurosurgery. The choice of approach is transsphenoidal preferably, so it is extremely important to know the anatomy of the sinuses when planning this approach. Materials and Methods: We describe the radiological anatomy studies Computerized tomography (CT) and Magnetic Resonance (MR) of 120 patients with pituitary adenoma who underwent transsphenoidal pituitary surgery, with special attention to the morphology of the sphenoid sinuses. Results: Neumatization type: pre-sellar 25 percent and 75 percent post-sellar; Septa: Single 45 percent, multiple 55 percent, mean diameters: 2.3 cm anteroposterior, transverse: 3.3 cm and vertical: 2.25 cm. The sphenoid sinuses with postsellar neumatization have anteroposterior diameter significantly higher (P < 0.005) than the pre-sellar. The sphenoid sinuses are single septum transverse diameter significantly higher (P < 0.007) than those with multiple septa. The 50 percent of the septa paramedian follow a path, and 50 percent is diverted to one of the carotid arteries. Conclusion: Results support the large sphenoid sinus anatomical variation is independent of patient sex, and we found that the relationship established by the intrasellar septa with intracranial vascular elements is very variable, this finding being paramount in preoperative planning. The findings by computed tomography (CT) may be comparable to that described by other authors in cadaveric dissections.

Reconstruction and measurement of cranial CT images of safety distance and angle in unilateral nasal transsphenoidal approach for pituitary surgery / 吉林大学学报(医学版)

Objective To measure the reconstructed cranial CT images,and to clarify the safety range of unilateral nasal transsphenoidal approach for pituitary surgery.Methods 100 normal pituitary cranial CT images were randomly selected,and the three-dimensional reconstruction was performed by using the CT images of perpendicular and parallel to the edge of the two eyes as base line, and the distance and angle in unilateral nasal transsphenoidal approach for pituitary surgery from the sagittal plane in the middle of the nasal meatus and the plane through the tip of the nose and both ends of dorsum sellae were measured,respectively. The angles and distances were compared when grouped the data by gender and age. Results Angle A1 (the angle between the tip of the nose and the tuberculum sellae and saddle back root line in the sagittal plane)in the sagittal plane of the middle nasal meatus was (11.22±1.35)°,95% confidence interval was 8.92°-13.76°degrees;the distance D1(the distance on the line between tuberculum sellae and saddle back root, and the line was formed by the plate contained the angle A1 and sellar floor)was (16.71 ± 2.07)mm,95% confidence interval was 13.11-19.93 mm.Angle A2 (the angle between the tip of the nose and the saddle back ends)which was in the plane through the tip of the nose and both ends of dorsum sellae was (8.91±1.19)°,95% confidence interval was 7.12°-10.72°;the distance D2(the distance on the line between the saddle back ends,and the line was formed by the plate contained the angle A2 and sellar floor)was (14.23±2.09)mm,95% confidence interval was 10.81-17.92 mm. The four parameter data was normally distributed,and there was no significantly statistic difference between different gender and ages (P>0.05).Conclusion The angle of the movement for unilateral nasal transsphenoidal approach for pituitary surgery operation in the sagittal plane in the middle of the nasal meatus should be less than (11.22 ± 1.35)°,and the distance of the movement should be less than (16.71±2.07)mm. The angle of the movement in the plane through the tip of the nose and both ends of dorsum sellae should be less than (8.9 1 ± 1.1 9 )°, and the distance of the movement should be less than (14.23±2.09)mm.

Outcomes following Purely Endoscopic Endonasal Resection of Pituitary adenomas.

Background: The use of endoscope for the management of pituitary adenoma is not new. The better magnification and illumination provided by the endoscope gives better outcome than microscopic pituitary surgery. Objective: To find out the benefits of endoscope in relation to microscopic surgery. Materials and Methods: We performed 45 cases of pituitary adenoma surgery by endoscopic endonasal approach from July 2008 to July 2010. Results: Forty five cases underwent endoscopic transsphenoidal approach. Gross total removal was done in 35 cases and subtotal removal was done in 10 cases. Residual tumours were seen in 10 cases (22%) in postoperative follow-up MRI scan. Visual improvement was satisfactory, and hormonal improvement of functional adenoma was nice. Postoperative visual acuity and visual field were improved in 75% cases. There were 37% cases of temporary diabetes insipidus and about 4.5% cases of permanent diabetes insipidus. The average duration of follow-up was 20 months. One patient required reexploration to correct visual deterioration in the immediate postoperative period. There were 4.5% cases of CSF leak and 6.6% mortality. Mortality was due to electrolyte imbalance and improper management of infection and hydrocephalus. Conclusion: Endoscopic endonasal pituitary surgery now has become a gold standard surgery for most of the pituitary adenomas because of its better advantages in relation to microscopic surgery and less complications and less hospital stay.

Avaliação do eixo hipotálamo-hipófise adrenal no diagnóstico e na remissão da doença de Cushing / Assessment of the hypothalamic-pituitary-adrenal axis in Cushing's disease diagnosis and remission

A doença de Cushing (DC) permanece um desafio médico com muitas questões ainda não respondidas. O sucesso terapêutico dos pacientes com DC está ligado à correta investigação do diagnóstico síndrômico e etiológico, além da experiência e talento do neurocirurgião. A adenomectomia hipofisária transesfenoidal constitui-se no tratamento de escolha para a DC. A avaliação da remissão da doença no pós-operatório e da recorrência em longo prazo constitui um desafio ainda maior. Especial destaque deve ser dado para o cortisol sérico no pós-operatório como marcador de remissão. Adicionalmente, o uso de corticoide exógeno no pós-operatório apenas em vigência de insuficiência adrenal tem sido sugerido por alguns autores como requisito essencial para permitir a correta interpretação do cortisol sérico nesse cenário. Neste artigo, revisamos as formas de avaliação da atividade da DC e os marcadores de remissão e recidiva da DC após a realização da cirurgia transesfenoidal.

Cushing's disease (CD) remains a medical challenge, with many questions still unanswered. Successful treatment of CD patients is closely related to correct approach to syndromic and etiological diagnosis, besides the experience and talent of the neurosurgeon. Pituitary transsphenoidal adenomectomy is the treatment of choice for DC. Assessment of remission after surgery and recurrence in the long term is an even greater challenge. In this regard, special attention should be paid to the role of postoperative serum cortisol as a marker of CD remission. Additionally, the postoperative use of exogenous glucocorticoids only in cases of adrenal insufficiency has been suggested by some authors as an essential practice to enable the use of serum cortisol in this scenario. In this article, we review the forms of evaluation of DC activity, and markers of remission and relapse of CD after transsphenoidal surgery.

Rathke's cleft cyst and partial feet adactyly: an unusual association

A 53 year-old woman presented a recurrent bifrontal headache of 2 years duration and bilateral progressive visual disturbance. The clinical and neurological examination showed a bilateral feet adactyly and bitemporal hemianopsia. The brain MRI demonstrated a Rathke's cleft cyst. The patient was operated by a transnasal endoscopic approach. It seems that this unusual association has never been described before.

Mulher de 53 anos com história recorrente de cefaléia com duração de 2 anos bilateral e progressiva, acompanhada de distúrbios visuais. O exame clinico e neurológico mostrou uma adactilia dos pés e hemianopsia bitemporal. A ressonância nuclear magnética cerebral mostrou um cisto de Rathke. A paciente foi operada por via transnasal endoscópica. Aparentemente esta é a primeira vez que esta associação é descrita na literatura.

Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4 percent and 28.6 percent (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9 percent vs. 73.9 percent; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4 percent (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.

O tratamento de escolha para a doença de Cushing (DC) ainda é a cirurgia transesfenoidal (CTE) para ressecção do adenoma hipofisário produtor de ACTH. Porém, a indicação de uma segunda CTE representa uma questão controversa, tanto nos pacientes não curados após a primeira cirurgia quanto nos casos de recidiva. Neste trabalho, relatamos os resultados da CTE em 108 pacientes com DC (totalizando 117 cirurgias). O tempo médio de seguimento foi de 6 anos. Critérios de cura: ocorrência de insuficiência adrenal (clínica ou laboratorial), período de dependência ao glicocorticóide, supressão do cortisol sérico pós-1 mg de dexametasona overnight e remissão clínica do hipercortisolismo. Foram avaliados 103 pacientes com DC submetidos à primeira CTE. Quatorze pacientes foram submetidos a uma segunda CTE (5 já tinham sido operados em outros centros; a primeira cirurgia não fora curativa em 5; 4 pacientes com recidiva da DC). Índices de cura: 85,4 por cento e 28,6 por cento (p < 0,001) após a primeira e segunda CTE, respectivamente. Nos microadenomas, remissão maior que nos macroadenomas (94,9 por cento vs. 73,9 por cento; p = 0,006). Nos pacientes com imagem hipofisária negativa, cura foi de 71,4 por cento (p = 0,003; vs. micro). Complicações pós-operatórias: diabetes insipidus transitório e definitivo, hipopituitarismo, acidente vascular cerebral e um óbito. Apenas a ocorrência de hipopituitarismo foi mais freqüente após a segunda CTE (p = 0,015). Assim sendo, a CTE para a DC representa uma terapêutica efetiva e segura. Os melhores índices de cura foram obtidos na primeira cirurgia e em microadenomas. O baixo índice de cura após a segunda CTE sugere que esta abordagem não deve ser considerada uma boa opção terapêutica quando a primeira cirurgia não for curativa.