Predictive model of resection in endoscopic endonasal approach for pituitary adenomas based on anatomical limits.

INTRODUCTION: The aim of this project is to study several anatomical-radiological features of pituitary adenomas obtained from preoperative radiological images and to analyze their relationship with the extent of resection achieved through the endoscopic endonasal approach. The second objective was to create a prediction model of the extent of resection. MATERIAL AND METHODS: We retrospectively evaluated 105 patients. Tumor volume, Knosp grade, suprasellar-diaphragm coefficient and invasion of the posterior compartment have been analyzed. The extent of resection was assessed by analyzing the postoperative magnetic resonance. We created the predictive scale using statistically independent variables. RESULTS: When each of the variables has been studied individually, a statistically significant value of all of them is appreciated to obtain a complete resection. However, only the Knosp grade and the suprasellar-diaphragm coefficient had a statistically significant value as independent variables. The sum of the Odds Ratio obtained from the Knosp scale, and the suprasellar-diaphragm coefficient gives the probability of complete resection. A new set of cases was employed to validate the scale. CONCLUSIONS: The cavernous sinus invasion and the newly designed suprasellar diaphragm coefficient are directly related to the extent of resection in pituitary adenoma surgery performed by a transellar endoscopic approach. Moreover, based on both radiologic factors, a predictive scale may predict the probability of complete resection in a series of patients.

Utilidad de la neuromonitorización vagal continua en cirugía tiroidea: experiencia y resultados en un hospital de tercer nivel / The role of continuous vagal intraoperative nerve monitoring in thyroid surgery: experience and results in a third-level hospital

Resumen Objetivo: La lesión del nervio laríngeo recurrente es una grave complicación en cirugía tiroidea. El propósito del presente estudio es analizar la utilidad de la neuromonitorización vagal continua intraoperatoria en un hospital terciario. Materiales y Método: Estudio observacional, analítico y retrospectivo que recoge pacientes intervenidos de cirugía tiroidea con neuromonitorización en un período de 14 meses. La pérdida de señal se define como amplitud final nerviosa < 100 ^V, realizándose laringoscopia postquirúrgica ante la sospecha de lesión nerviosa. El análisis estadístico se realizó con el programa SPSS® V25,0, con p < 0,05. Resultados: Se incluyeron 120 pacientes intervenidos, registrándose en el 24,2% pérdida de señal. Factores de riesgo para lesión fueron bocio intratorácico (OR 5,31; IC 95% 1,56-17,99; p = 0,007), cirugía cervical previa (OR 5,76; IC 95% 0,64-51,97; p = 0,119) y patología maligna (OR 1,44; IC 95% 0,16-12,79; p = 0,743). Fue posible el cambio de estrategia quirúrgica en 7 casos. En el seguimiento posterior se cuantificó parálisis recurrencial transitoria en 27 pacientes y permanente en 4. Discusión: La neuromonitorización parece reducir la incidencia de parálisis laríngea porque aumenta la seguridad en la identificación del nervio recurrente y reduce su manipulación durante la cirugía. Conclusiones: La neuromonitorización intraoperatoria es útil para identificar el nervio laríngeo recurrente y advierte del riesgo potencial de lesión, permitiendo cambiar la estrategia quirúrgica para evitar la parálisis bilateral de cuerdas vocales.

Aim: Recurrent laryngeal nerve injury is a serious complication in thyroid surgery. The purpose of the present study is to analyze the use of intraoperative continuous vagal neuromonitoring in a tertiary hospital. Materials and Method: Observational, analytical and retrospective study that includes patients who underwent thyroid surgery with neuromonitoring in a period of 14 months. Loss of signal is defined as final nerve amplitude < 100 ^V, and postsurgical laryngoscopy is performed due to suspicion of nerve injury. Statistical analysis was performed with the SPSS® V25.0 program, with p < 0.05. Results: 120 operated patients were included, registering loss of signal in 24.2%. Risk factors for injury were intrathoracic goiter (OR 5.31; 95% CI 1.56-17.99; p = 0.007), previous cervical surgery (OR 5.76; 95% CI 0.64-51.97; p = 0.119) and malignant pathology (OR 1.44; 95% CI 0.16-12.79; p = 0.743). A change in surgical strategy was possible in 7 cases. In the subsequent follow-up, transient recurrent paralysis was quantified in 27 patients and permanent in 4. Discussion: Neuromonitoring seems to reduce the incidence of laryngeal paralysis because it increases the security in the identification of the recurrent nerve and reduces its manipulation during surgery. Conclusions: Intraoperative neuromonitoring is useful to identify the recurrent laryngeal nerve and warns of the potential risk of injury, allowing to change the surgical strategy to avoid bilateral vocal cord paralysis.

Impact of a clinical pathway on cardiovascular risk in patients with diabetes.

OBJECTIVES: Clinical pathways (CPs) are interventions that target the way clinical practice guidelines are applied. They can be implemented in different diseases, including diabetes. In this study we evaluated the impact of the implementation of a CP in the control of cardiovascular risk factors and the occurrence of new events in patients with type 2 diabetes. METHODS: A pre- and post-intervention population-based study in a Spanish region, conducted in 2014-2016. Variables before and after the intervention were: screening; good control of diabetes, dyslipidemia and hypertension; hypoglycemia and hyperglycemic decompensation; obesity; cardiovascular events; diabetic ketoacidosis; hyperglycemic and hypoglycemic coma. Proportional differences and parameters of clinical relevance (absolute and relative risk reduction, relative risk and number needed to treat) were calculated. RESULTS: The CP achieved an improvement in all outcomes, reducing events and increasing control of different cardiovascular parameters. The greatest improvement was in metabolic control (HbA1c) (37.1% in younger patients and 34.0% in older patients) and screening (5.4%). Indicators of clinical relevance showed that the CP was able to improve metabolic control of diabetes with little effort and great benefit. CONCLUSION: The CP was of considerable benefit to metabolic control as well as control of dyslipidemia and obesity. Screening for diabetes also benefitted. The CP decreased the incidence of events, especially of angina pectoris.

Proposal of a clinically relevant working classification of pituitary neuroendocrine tumors based on pituitary transcription factors.

The immunohistochemistry (IHC) characterization of pituitary transcription factors (PTFs) PIT1, TPIT, and SF1, which enable the identification of three different adenohypophyseal cell lines, has been incorporated into the latest classification system of the World Health Organization (WHO) for pituitary adenomas. This change overturns the concept of the adenoma as solely a hormone producer and classifies these tumors based on their cell lineage. The aim of the study was to provide a diagnostic algorithm, based on IHC expression of hypophyseal hormones with potential use in diagnostic practice, contributing to an improved classification of pituitary adenomas. Our sample included 146 pituitary adenomas previously classified based on hormonal subtypes by IHC (former 2004 WHO criteria) and re-evaluated after the IHC quantification of PIT1, TPIT, and SF1 expression, under WHO 2017 recommendations. We assessed the correlation between expression of PTFs and the classification as per hormonal IHC and correlated clinicopathological profiles based on PTFs. The IHC study of PTFs allowed reclassification of 82% of tumors that were negative for all pituitary hormones, with 21 positive cases for SF1 (reclassified as gonadotroph tumors), 1 positive case for TPIT (reclassified as a corticotroph tumor), and 4 positive cases for PIT1. Using SF1 enabled detection of a substantial portion of gonadotroph tumors, reducing the estimated prevalence of null cell tumors to less than 5%, and identification of plurihormonal pituitary neuroendocrine tumors with PIT1-SF1 coexpression and hormone-negative PIT1s, a group in which we did not observe differences in the clinical behavior compared with the rest of the tumors of the same cell lineage.Our results suggest that applying a diagnostic algorithm based on the study of PTFs could contribute to improving the classification of pituitary adenomas. By adding TPIT assessment, we propose a two-step algorithm, with hypophyseal hormones being used in a selective modality, depending on initial results.

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.

[Endonasal endoscopic surgery in pituitary adenomas: Surgical results in a series of 86 consecutive patients]. / Cirugía endoscópica endonasal en adenomas hipofisarios: resultados quirúrgicos en una serie de 86 pacientes consecutivos.

INTRODUCTION: The endoscopic endonasal approach has become the gold standard for the surgical treatment of pituitary adenomas. OBJECTIVES: The aim of this study is to present the results obtained in our hospital in purely endoscopic surgery of pituitary adenomas. METHODS: From February 2011 to August 2016, we conducted a prospective study on a series of 86 patients with pituitary adenoma, all of whom underwent surgery with a purely endoscopic endonasal approach. The 'four hands-two nostrils' technique was performed in all cases by a surgical team composed of an ENT surgeon and a neurosurgeon. Mean follow-up was 32 months. All patients were evaluated according to clinical, radiological and endocrinological criteria. RESULTS: In our series, 53% were women and 47% men. The age ranged from 14 to 84 years of age, with a mean of 54 years of age. The most common initial symptom was visual deficit (42%), followed by hormonal hyperfunction (21%), with acromegaly being the most common clinical syndrome. The most common tumours were non-functioning tumours (73%), while GH-secreting tumours (65%) were the most common functioning adenoma. Regarding tumour size, 76% were macroadenomas, 11% microadenomas and 13% giant adenomas. Approximately 63% of the adenomas exhibited suprasellar extension and 37% involved invasion of the cavernous sinus (Knosp grade ≥3). Total excision was achieved in 77% of the cases. After the intervention, visual improvement was achieved in 91% and remission of endocrine hyperfunction in up to a 73% of cases. The most common complication was anterior pituitary insufficiency of at least one axis (9%). There were no cases of postoperative cerebrospinal fluid fistula. CONCLUSIONS: In terms of surgical quality, our results are similar to those of published series, and demonstrate the efficacy and safety of the endoscopic endonasal approach as the surgical treatment of choice for pituitary adenomas. However, further studies with a higher sample size are necessary to obtain clinically significant results.

Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence.

Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion and recurrences. Angiogenesis is regarded as an essential step in the formation of solid tumors. The aim of this study is to find out whether angiogenic factors may have information about the aggressiveness of PA that could be useful in determining the frequency of follow-up and whether adjuvant therapy is necessary. In this retrospective descriptive study, we evaluated vascular endothelial growth factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46 human PA samples. Clinical data, histological subtype and radiologic characteristics were studied to determine the associations between the variables and the pre-operative behavior of the tumor. In addition, we monitored 12 patients without adjuvant post-operative therapies over 46 months after surgery, determining progression of tumor remnants and its association with these markers. VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF demonstrates different expression between histological subtypes (p = 0.036). The extension at magnetic resonance imaging showed that VEGF expression was related to suprasellar extension (p = 0.007), being expressed more on tumors with extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a 27.5 times increased risk of extrasellar growth when VEGF expression exceeds 0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results suggest that the expression of VEGF and its receptor could be a marker for poor outcome after partial tumor resection. These data should be considered in future studies evaluating angiogenic factors as therapeutic targets in patients with PA.

[Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas]. / Papel de pituitary tumour-transforming gene (PTTG) en los adenomas hipofisarios.

The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours.

Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens.

RATIONALE AND OBJECTIVE: The treatment of active moderate-severe Graves' ophthalmopathy (GO) is based on the administration of highdose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens. MATERIAL AND METHODS: We carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderatesevere GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv (n=13); and regimen B (16 weeks): 4 cycles of 15 mg/kg, followed by 4 cycles of 7.5mg/kg, for a cumulative dose of 90 mg/kg (range, 4.9-7.4 g) (n=11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence). RESULTS: Mild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension - with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p>0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO. CONCLUSIONS: The treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A.

[Hypogonadism, erectile dysfunction and endothelial dysfunction among HIV-infected men]. / Hipogonadismo, disfunción eréctil y disfunción endotelial en varones con infección por el virus de la inmunodeficiencia humana.

HIV-associated hypogonadism is known to be a prevalent endocrine disorder, with a multifactorial etiology. Low testosterone levels are associated with decreased muscle mass, exercise capacity loss, erectile dysfunction, cognitive impairment, depression and decreased quality of life. In the same way, hypogonadism in HIV-infected men is associated with decreased muscle mass quantity and function, changes in corporal fat mass distribution and quantity, secretion of adipocytokines and endothelial dysfunction. This combined effect renders the entire body less sensitive to insulin, promoting development of atherosclerosis and glucose metabolism disorders. The clinical presentation is non-specific and hypogonadism screening scales are not useful in this population. Diagnostic procedures must include determination of free testosterone (FTc) in any HIV-infected men at the time of first HIV diagnosis and periodically, because of the clinical implications and the absence of specific predictive disease factors. Substitutive hormonal treatment must be offered only for HIV-infected men with FTc under reference levels and when reversible causes have been ruled out. Metabolic impact of hypogonadism suggests the incorporation of low testosterone levels to the list of cardiovascular risk factor in HIV-infected men.

Primary hyperparathyroidism due to parathyroid carcinoma associated with pulmonary embolism.

Parathyroid carcinoma (PC) is an uncommon disease affecting 0.5-5% of all patients with primary hyperparathyroidism. PC is characterized by the association of severe symptoms of hypercalcemia, high serum calcium and parathyroid hormone (PTH) concentrations and a palpable neck mass. Definitive diagnosis can only be made by histological study after surgery. We report the case of a 77-year-old man admitted to our hospital due to pulmonary embolism and hypercalcemia. The patient was initially diagnosed with primary hyperparathyroidism, but displayed the atypical clinical features described above. Due to clinical suspicion of PC, a surgical procedure was carried out. Diagnosis of parathyroid carcinoma was confirmed by histopathologic study.

Clinical practice guideline for hypotalamic-pituitary disturbances in pregnancy and the postpartum period.

During pregnancy, the body undergoes a major adaptation process as a result of the interaction between mother, placenta and fetus. Major anatomical and histological changes are produced in the pituitary, with an increase of up to 40% in the size of the gland. There are wide variations in the function of the hypothalamus-pituitary-thyroid axis that effect iodine balance, the overall activity of the gland, as well as transport of thyroid hormones in plasma and peripheral metabolism of thyroid hormones. The incidence of goiter and thyroid nodules increases throughout pregnancy. The management of differentiated thyroid carcinoma should be individually tailored according to tumoral type and pregnancy stage. Given the effects of hypothyroidism on fetal development, both the diagnosis and appropriate therapeutic management of thyroid hypofunction are essential. The most important modification to the hypothalamus-pituitary-adrenal axis during pregnancy is the rise in serum cortisol levels due to an increase in cortisol-binding proteins. Although Cushing's syndrome during pregnancy is infrequent, both diagnosis and treatment of this disorder are especially difficult. Adrenal insufficiency during pregnancy does not substantially differ from that occurring outside pregnancy. However, postpartum pituitary necrosis (Sheehan's syndrome) is a well-known complication that occurs after delivery and, together with lymphocytic hypophysitis, constitutes the most frequent cause of adrenal insufficiency. The management of prolactinoma during pregnancy requires suppression of dopaminergic agonists and their reintroduction if there is tumoral growth. Notable among the neuropituitary disorders that can occur throughout pregnancy is diabetes insipidus, which occurs as a consequence of increased vasopressinase activity.

Clinical practice guideline for the diagnosis and treatment of hypophysitis.

Hypophysitis are a group of inflammatory lesions affecting the pituitary gland and pituitary stalk. These lesions should be included in the differential diagnosis of sellar masses. There are three types of primary hypophysitis: lymphocytic, granulomatous and xanthomatous. Lymphocytic hypophysitis is the most frequent form of chronic pituitary inflammation and is believed to have an autoimmune origin. This form characteristically affects women during the peripartum, with diverse types of pituitary deficiency, especially ACTH deficiency, and frequently there are other associated autoimmune processes. Lymphocytic hypophysitis can affect the anterior pituitary only, the infundibular stalk and posterior lobe of the pituitary (infundibuloneurohypophysitis), or the entire pituitary (panhypophysitis). Clinically, lymphocytic hypophysitis can manifest with compression symptoms, hypopituitarism, diabetes insipidus or hyperprolactinemia. The imaging technique of choice is magnetic resonance imaging, which helps to characterize the sellar lesion. Treatment includes replacement of the functional pituitary deficiency and the use of corticosteroids, generally at high doses. Surgical treatment is reserved for patients unresponsive to conservative therapy. Granulomatous hypophysitis can be of known etiology, whether infectious (currently highly infrequent) or non-infectious (ruptured Rathke's cyst, etc.). Granulomatous hypophysitis of unknown etiology is manifested by the presence of idiopathic granulomas. Xanthomatous hypophysitis is characterized by a histiocytic infiltrate with cystic characteristics on imaging. Secondary hypophysitis is due to pituitary inflammation caused by surrounding lesions or can form part of systemic diseases.

Silent corticotroph adenomas of the pituitary gland: apropos of two cases.

Clinically silent corticotroph adenomas are rare. The clinical course of these tumors varies: while some have an insidious course, others behave aggressively, especially during tumoral recurrence. Given the absence of clinical and biochemical features of hypercortisolism, the definitive diagnosis is histological.