Pre-and post-surgical non-functional pituitary adenomas and their relationship with high levels of serum glucose.

OBJECTIVES: This clinical, analytical, retro-prospective, auto-controlled, not randomized, and not blinded study, aimed to investigate the association of changes in the serum glucose levels with the pre-and-post changes in the size tumor in mm3 in the Non-Functional pituitary adenomas. METHODS: Pre-and post-surgical MRI, as well as the measurements in the serum glucose levels and immunohistochemical techniques were performed in all the patients in the study, with a mean followed-up until 208.57 days. A comparison was made between the reductions in tumor size of hormonally active pituitary adenomas (HSPAs) vs NFPAs. RESULTS: Seventy-four patients were included in this study, of whom, 46 were NFPAs. The decrease in the NFPAs tumor size after surgery was statistically significant (P ≤ 0.0001). The Mean of the differences of both type of tumors in mm3 were -9552 ± 10287. Pre-surgery, the mean of the HSPAs were 8.923 ± 2.078; and the NFPAs were 14.161 ± 1.912. The differences in the tumor size were statistically significant (p = 0.039). Post-surgical, the mean of the HSPAs were 2.079 ± 971, with a (p = 0.14): and the NFPAs were 4.609 ± 1.205. After surgery of the NFPAs, most of the patients-maintained serum levels ≤ 100 mg/dL, with a statistical significance (P ≤ 0.0003). CONCLUSION: This study demonstrates for the first time the correlation between the presence of pre-and post- surgical changes in the NFPAs, with modifications in the levels of serum glucose, and the comparison, pre- and post-surgical between the tumor size of HSPAs and NFPAs.

Postoperative Third Nerve Palsy after Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma: Elucidating its Mechanism.

Third nerve palsy is a rare complication of transsphenoidal surgery and has been merely mentioned in different studies, but there is not any rigorous analysis focusing on this particular complication. The purpose of this study is to analyze this complication after transsphenoidal surgery for a pituitary adenoma to better understand its pathophysiology and outcome. The authors retrospectively analyzed 3 cases of third nerve palsy selected from the 377 patients operated via a transsphenoidal route between 2012 and 2021 at FLENI, a private tertiary neurology and neurosurgical medical center located in Buenos Aires, Argentina. The three patients who presented this complication were operated on via an endoscopic approach. It was observed that an extension into the cavernous sinus (Knosp grade 4) and to the oculomotor cistern was present in the three patients. The deficit was apparent immediately after surgery in two patients. For these two patients, the supposed mechanism of ophthalmoplegia was an intraoperative nerve lesion. The other patient became symptomatic in the 48 h following the surgery. The mechanism implied in this case was intracavernous hemorrhagic suffusion. The latter patient completely recovered the third nerve deficit in the 3 months that followed, while the other two recovered after 6 months postoperative. Oculomotor nerve palsy after transsphenoidal surgery is a very rare complication and appears to be transient in most cases. The invasion of both the cavernous sinus and the oculomotor cistern seems to be a major factor in its physiopathology and should be preoperatively analyzed on magnetic resonance imaging (MRI); recognizing such extension should play an important role in the surgeon's operative considerations.

Pregnancy after pituitary surgery does not influence the recurrence of Cushing's disease.

PURPOSE: Pregnancy is associated with the activation of the hypothalamus-pituitary-adrenal axis, which can cause a misdiagnosis of Cushing's syndrome. The aim of this study is to evaluate the impact of pregnancy after pituitary surgery on the recurrence rate in Cushing's disease (CD) patients. METHODS: This was a retrospective study in a tertiary center. Between 1990 and 2020, 355 CD patients underwent pituitary surgery. Of those, we included 113 female patients who were ≤ 45 years old (median age of 32 years, 14-45), PS remission, a follow-up of ≥6 months (median of 122 months, 6-402) and an available obstetric history. Recurrence was defined as the diagnosis of Cushing's syndrome via at least two altered first-line methods. The patients were divided into two subgroups according to pregnancy: no pregnancy or pregnancy prior to CD diagnosis (NP/PP) and pregnancy after CD pituitary surgery (PA). RESULTS: Overall, recurrence occurred in 43 out of 113 patients (38%). A higher recurrence rate was seen in the PA subgroup (11/22, 50%), but there was no significant difference between the NP/PP subgroup (32/91, 35%). No difference in survival-free recurrence (SFR) was found between NP/PP and PA subgroups. The lower SFR was related to a higher PS plasma ACTH and normal pituitary at pathological analyses. CONCLUSIONS: There was no difference in the recurrence rate in patients according to pregnancy history. Other studies with higher numbers of patients are needed to confirm these data.

Endoscope-assisted contralateral transmaxillary approach to the clivus and the hypoglossal canal: technical case report.

Clival lesions are still considered surgically complex due to their anatomical location. Critical structures, such as the internal carotid arteries (ICAs), cavernous sinuses, cranial nerves, and brainstem, may be encased within the lesion. Although advances in endoscopic endonasal approaches have provided new routes to these lesions, exposure and resection of clival tumors through the endonasal route remain a technical challenge. Here, the authors report a left-sided endoscopic transmaxillary approach to access the right aspect of the clivus and the hypoglossal canal.A 35-year-old woman presented with progressive right 6th cranial nerve palsy. MRI revealed a contrast-enhancing right petroclival chondrosarcoma that involved Meckel's cave and extended into the right hypoglossal canal. An endoscopic-contralateral-transmaxillary approach through a left sublabial incision was used to access the right petroclival region and right hypoglossal canal. A left maxillary osteoplastic flap was elevated to expose the left maxillary sinus. This was followed by a left medial maxillectomy, gaining access to the left posterior nasal cavity. The posterior third of the left inferior turbinate and nasal septum were removed to access the right side of the petroclival region. Near-total resection was achieved without any vascular or neurological complications. A thin shell of residual tumor was left behind due to involvement of vital structures, such as the ICA, and further treated with proton-beam radiotherapy.The endoscopic-contralateral-transmaxillary approach provides a direct surgical corridor and good lateral visualization of the skull base vasculature. This approach allows wide maneuverability around the ICA and hypoglossal canal, which, in this case, allowed maximal tumor resection with full preservation of neurological function.

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.

Postoperative Diabetes Insipidus and Hyponatremia in Children after Transsphenoidal Surgery for Adrenocorticotropin Hormone and Growth Hormone Secreting Adenomas.

OBJECTIVES: To define the incidence and risk factors of postoperative sodium alterations in pediatric patients undergoing transsphenoidal surgery (TSS) for adrenocorticotropic hormone and growth hormone secreting pituitary adenomas. STUDY DESIGN: We retrospectively reviewed 160 patients ≤18 years of age who had TSS for pituitary adenomas at our institution from 1999 to 2017. Variables included daily serum sodium through postoperative day 10, urine specific gravity, and medications administered. We examined associations between sex, repeat surgery, manipulation of the posterior pituitary (PP), tumor invasion into the PP, tumor type and size, cerebrospinal fluid (CSF) leak, lumbar drain insertion, body mass index, puberty, and development of diabetes insipidus (DI) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). RESULTS: Mean age was 12.9 ± 3.4 years (female = 81). Patients had adrenocorticotropic hormone (150/160) and growth hormone (10/160) producing adenomas. Forty-two (26%) patients developed DI. Among the 37 of 160 who required desmopressin acutely, 13 of 37 required it long term. Risk of long-term need for desmopressin was significantly higher in patients who had CSF leak 9 of 48 (P = .003), lumbar drain 6 of 30 (P = .019), manipulation 11 of 50 (P < .001), or invasion 4 of 15 (P = .022) of the PP. Sixty patients developed hyponatremia, 19 because of SIADH, 39 to hypotonic fluids and 2 to cerebral salt wasting syndrome. Patients with SIADH were placed on fluid restriction; 1 received salt tablets. CONCLUSIONS: Among 160 children who underwent TSS for pituitary adenomas, the incidence of DI and SIADH after TSS was 26% and 14%, respectively. Combined risk factors for DI and/or SIADH include female sex, manipulation of and/or tumor invasion into the PP, and CSF leak or lumbar drain. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00001595 and NCT00060541.

Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing's disease harbouring microadenomas or macroadenomas.

PURPOSE: Pituitary macroadenomas (MACs) represent 10-30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients. METHODS: Retrospective study with 317 CD patients (median 32 years old, range 9-71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC. RESULTS: Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI. CONCLUSIONS: Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate.

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.

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.

Long-term control of macroprolactinomas.

Hyperprolactinemia is the most prevalent hypothalamic-pituitary dysfunction, with prolactinomas being its main cause. Microprolactinomas (diameter < 10 mm) represent approximately 60% of the prolactin-secreting adenomas, and are far more common in women than in men, whereas macroadenomas have roughly the same prevalence in both genders. The treatment of patients harboring macroprolactinomas is highly gratifying, with more than 80% of them adequately controlled by dopamine-agonist (DA) drugs: cabergoline being the most efficacious to date. Emerging evidence points to remission of the disease after long-term DA therapy in a significant number of patients. The remaining cases, mainly those with enclosed tumors, may be treated successfully by pituitary surgery. Radiotherapy is reserved for cases with dopaminergic drug resistance not surgically cured. The development of new therapeutic approaches may turn the control of the subset of macroprolactinomas refractory to both DA and surgery into reality.

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.