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Transient Delayed Hyponatremia after Transsphenoidal Surgery: Attempting to Enlighten the Epidemiology and Management of a Still-Obscure Complication
No full textAlthough the occurrence of transient delayed hyponatremia after transsphenoidal surgery is well known, the need for more and better knowledge of this phenomenon remains. The vast majority of patients have asymptomatic hyponatremia, which explains the great disparities reported in the prevalence of the disorder, from 2% to 35% on the basis of different inclusion criteria.1-12 The more the patients perform daily venous samples for serum sodium assay during the postoperative period, the more frequent the occurrence of asymptomatic hyponatremia becomes, because a large number of cases will be discovered.4,11
It is well known that delayed hyponatremia after transsphenoidal surgery, defined as a serum sodium level of less than 135 mmol/L on or after postoperative day 3, usually occurs around postoperative day 7 (between 3 and 11 days after surgery) as an isolated entity or, much more rarely, as an interphase in the triphasic postoperative diabetes insipidus. As a result, hyponatremia often occurs when the patient already has been discharged, making the postoperative care troublesome. Furthermore, in the case of readmission because of delayed hyponatremia after transsphenoidal surgery, the cost of overall care of this patient population increases relevantly.
For a long time after Cusick et al.1 reported the inappropriate secretion of antidiuretic hormone (SIADH) as the possible cause of delayed symptomatic hyponatremia after transsphenoidal surgery in 1984, the debate regarding the pathophysiology of the disorder had a checkered history. Given the whole body of evidence collected during the last 3 decades, the syndrome of SIADH would seem the more plausible cause of hyponatremia in this setting1-12; however, some studies in which the authors suggest cerebral salt wasting syndrome (CSWS) as another possible cause have also been published.13,14 The most likely explanation for these puzzling findings is the difficulty from the patient bedside in evaluating the extracellular volume status, which highlights the real difference between these 2 conditions. On the other hand, when faced with a hyponatremic patient, the physician has to bear in mind that the clinical evaluation of the extracellular volume status is mandatory for a correct diagnosis and an effective treatment. Both SIADH and CSWS share similar laboratory tests (plasma osmolality, urinary osmolality, and urinary sodium concentrations) but differ in the extracellular volume status, which is expanded in the former (despite the patient is clinically euvolemic) and depleted in the latter.
Some retrospective studies have identified factors associated with increased risk for delayed hyponatremia after transsphenoidal surgery, including sex (female), tumor size, hypopituitarism, transient diabetes insipidus, and Cushing disease.5,6,8,10,13,15,16 Concerns have been raised, however, about the real impact of these findings, and no consensus exists. The group of patients affected with Cushing disease, for example, could represent a distinct cohort, in which the postoperative hyponatremia may have a different pathophysiology, namely the secondary adrenal insufficiency occurring after remission of Cushing disease. Keeping in mind, however, the relevant role of delayed hyponatremia in the postoperative management and the additional cost of this complication, there is no doubt that the identification of predictive factors may be relevant to identify patient subpopulations at greater risk and keep them under a strict surveillance after discharge.
In January 2016, Bohl et al.17 identified delayed symptomatic hyponatremia as the primary cause of unplanned readmission after transsphenoidal surgery for pituitary tumors. In their retrospective cohort of 303 patients, 27 (8.9%) were readmitted within 30 days. Of these, 15 (55.6%) had delayed hyponatremia. As a result, of all the patients discharged after pituitary surgery, 5% (15/303) were readmitted because of symptomatic hyponatremia. Other less-frequent causes of unplanned readmission were diabetes insipidus (4 cases), secondary adrenal insufficiency (2 cases), cerebrospinal fluid leak, epistaxis, cardiac arrhythmia, pneumonia, urinary tract infection, and hypoglycemia (1 case each). Another recent retrospective cohort of 466 consecutive patients who underwent endoscopic transsphenidal surgery showed a slightly greater readmission rate for epistaxis than hyponatremia (2.1% and 1.5%, respectively).18
Some years ago, we evaluated retrospectively the prevalence, risk factors, course, and management of symptomatic delayed postoperative hyponatremia in our cohort of 1098 consecutive patients who underwent pituitary surgery by endoscopic endonasal approach from 1998 to 2010, and the results of the study were presented in 2011 at the Italian Society of Endocrinology's 35th Meeting in Pescara, Italy. Ninety-five patients were excluded on the basis of the following exclusion criteria: postoperative triphasic diabetes insipidus, diuretic treatment, drug-induced SIADH, and scant laboratory data. Therefore, a total of 1003 patients (median age, 50 years, range, 3–89 years; 52% females; 87% pituitary adenomas; 5% craniopharyngiomas; 5% Rathke cleft cysts; 2% metastases; 1% meningiomas) were eligible for the study. Forty-one patients (4%) developed symptomatic delayed hyponatremia, which occurred after discharge in all patients but 3. Nadir of medians of serum sodium (124 mmol/L) occurred on postoperative day 8. Both the clinical assessment of extracellular volume status and laboratory tests were consistent with the diagnosis of hypotonic hyponatremia due to SIADH in all cases (no case of CSWS was recorded in our cohort). Age, tumor size, and tumor type (including corticotroph cell adenoma associated with Cushing disease) did not correlate with the development of symptomatic hyponatremia. Interestingly, female patients were more likely to develop symptomatic hyponatremia than males (female to male ratio: 3.1; P < 0.05). Fluid intake restriction was successfully used in 16 patients (39.1%); the remaining 25 (60.9.%) were treated with 3% NaCl hypertonic saline infusion (0.5–2 mL/kg/hour). No case of osmotic demyelination syndromes occurred. The recommended limits of correction in serum sodium concentration in the first 24 hours were 6–8 mmol/L. The apparently high percentage of patients treated with hypertonic saline was attributable to the inclusion criteria. Indeed, we evaluated only patients with symptomatic hyponatremia who were readmitted after transsphenoidal surgery. We continue to be successful in using the same protocol for the management of transient delayed hyponatremia after transsphenoidal surgery. As a matter of fact, the choice of treating patients with severe symptoms of hyponatremia (vomiting, abnormal somnolence, cardiorespiratory distress) with 3% NaCl hypertonic saline independently by the biochemical degree of hyponatremia is now accepted widely and the recommended limits of correction of serum sodium as well.19
To date, the systematic review recently published in WORLD NEUROSURGERY by Cote et al.20 represents a more accurate and updated review of the literature on the delayed hyponatremia after transsphenoidal surgery. The authors have chosen 10 studies for a total of 2947 patients. Despite some limitations of the studies, mainly from the heterogeneity of the including criteria, which makes the pool analysis not so meaningful as expected, the authors have found a number of predictive factors for developing delayed postoperative hyponatremia: young age, female sex, greater tumor size, greater rate of decline of serum sodium, and Cushing disease. Again, the heterogeneity of the inclusion criteria remains the main concern regarding the possibility of considering their findings to be conclusive. However, the systematic review of Cote et al. represents a key step toward improving the postoperative management of postoperative hyponatremia in patients undergoing transsphenoidal surgery. Furthermore, the authors encourage the research in this field, with the aim to recognize the causes and the mechanisms of this fascinating electrolyte disorder.
One way to do so is to design a large prospective cohort study that allows investigators to avoid confounding factors, such as uncertainties in the postoperative management of patients with Cushing disease, lack of assessment of extracellular volume status, and scant laboratory data (urinary osmolality and urinary sodium, for example, are mandatory for a correct diagnosis of hyponatremia, but these data sometimes have not been recorded in previous studies), in order to ascertain the epidemiology, the proper management, and the causes of this still-obscure and challenging postoperative complication
Terapia della pubertà precoce vera idiopatica. Descrizione di un caso clinico.
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Pituitary metastases: Role of surgery
No full textObjective: To evaluate the clinical and radiographic manifestations of pituitary metastases (PM), discuss the role of surgery, and briefly review the pertinent literature. Methods: At a single institution between January 1992 and July 2011, 15 patients with PM were surgically treated (all cases were confirmed by histologic analysis). Of patients, 14 complained of visual impairment, 8 complained of headache, 4 complained of ophthalmoplegia, and 11 complained of endocrine disturbances manifesting as diabetes insipidus (7 patients) and anterior hypopituitarism (4 patients). Results: After transsphenoidal surgery, visual disturbances improved in 12 cases, headache improved in 5 cases, and ophthalmoplegia improved in 2 cases. Endocrinologic function remained unchanged in all cases. The mean survival time was 11.8 months (range, 3-43 months); one patient still survives after 33 months. Conclusions: The study cohort includes patients representing two clinical situations: (i) patients with a preoperative suspicion of PM and (ii) patients in whom the metastasis was an unexpected finding during surgery performed for a presumed pituitary adenoma. The former situation is indicative of the possibilities and limits of surgery, which may confirm the diagnosis but is only palliative, improving quality of life without improving life expectancy. The latter situation reveals how misleading clinical and radiographic features of PM can be. Considering these results, surgical treatment of PM should be specifically decided based on patient performance status, tumor staging, and patient preference. © 2013 Elsevier Inc. All rights reserved
Syndrome of inappropriate antidiuresis as a maladaptive stress response shared by coronavirus disease 2019 and other cytokine storm disorders
No full textn.a
Tuberculum sellae meningioma growing during pregnancy: A difficult decision-making process
No full textA 43-yr-old woman presented to us 32 wk into her second pregnancy with a 2-wk history of progressive visual impairment (consisting of bitemporal emianopia and visual acuity decrease to 1/10 in the left eye and 4/10 in the right eye) due to a tuberculum sellae meningioma (TBM) (Fig. 1A). The diagnosis was based on the presence of typical radiological features of a meningioma overlying a normal-sized sella with a preserved pituitary gland. She was given oral dexamethasone to accelerate the fetal lung maturation. A healthy boy was born at 34 wk gestation by cesarean section. After delivery, visual disturbances did not improve, and the patient underwent an endoscopic transsphenoidal transplanum/transtuberculum approach (ETTA), obtaining radical removal of the meningioma. Histological examination showed a meningotheliomatous meningioma with marked expression of progesterone receptors (Fig. 2). The postoperative course was uneventful, and she was discharged home on d 5 with complete recovery of her visual function. The patient did not show hypothalamic/pituitary dysfunction during or after pregnancy. Three months later, magnetic resonance imaging confirmed the radical removal of the tumor (Fig. 1B). When last seen 5 months after surgery, she was in good clinical condition. To our knowledge, 13 other cases of TBM growing during pregnancy have been reported (1–4), but our patient was the first to be treated by ETTA, a minimally invasive approach that favored a prompt return home of the mother to her child. The high expression of progesterone receptor in the specimen (Fig. 2) confirms the physiopathological mechanism suggested by other authors to explain the rapid growth of the tumor during pregnancy (1–4). Interestingly, supporting this hypothesis, regression of multiple intracranial meningiomas after discontinuation of long-standing use of megestrol acetate has been recently reported (5)
Endoscopic transsphenoidal approach as a promising surgical option in the treatment of craniopharyngioma
Full text link10.1530/endoabs.32.P85
Pituitary centers of excellence
No full textTo the Editor:
We read with interest the article by McLaughlin and colleagues1 about Pituitary Centers of Excellence (PCOEs), along with the outstanding comments published in the same issue of the journal. We agree with the authors that PCOE may be defined as a cohesive team of specialists (neurosurgeons, endocrinologists, otorynolaryngologists, neuro-ophthalmologists, neuroradiologists, neuropathologists, radiation oncologists) who promote collaboration and apply best practices to improve results and overall outcomes in patients with pituitary tumors and related disorders. Again, in accordance with McLaughlin and colleagues, the 3 primary missions to be fulfilled by the centers to be recognized as a PCOE are the following: providing multidisciplinary, optimal clinical care to patients with pituitary tumors and related disorders; providing residency, fellowship training, and/or continuing medical education and patient support; and contributing to research in the field of pituitary disorders
The changing faces of corticotroph-cell adenomas: the role of proconvertase 1/3
No full textIntroduction: The possible change in the pattern of hormonal secretion by pituitary tumours is a very intriguing issue indeed, notably in the case of corticotroph-cell adenomas.
Methods/design: We retrospectively reviewed the records of 1259 consecutive endoscopic endonasal surgical procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were ACTH-secreting adenomas associated with Cushing’s disease (CD) and 44 were silent corticotroph-cell adenomas (SCA). During the follow-up, seven patients (four men and three women) showed a transformation of their clinical expression from SCA to CD or, more rarely, vice versa. Of these, to date only three patients with corticotroph-cell adenomas changing their pattern of hormonal secretion during the follow-up were re-operated. Then, we examined the expression of proconvertase 1/3 (PC1/3), which plays an important role in the POMC processing within the pituitary, in tissue specimens obtained from these three patients with SCA that had developed clinical and laboratory features of CD at the time of recurrence, using both immunohistochemistry and quantitative real time-PCR.
Results: The data indicated that the immunohistochemical PC1/3 expression was negative or weak and focally positive in tissue specimens obtained in the three patients at the time of first operation (SCA), whereas we observed a strong expression in the majority of the neoplastic cells in the same three patients at the time of recurrence, when they had become CD. The PC1/3 expression, as evaluated using immunohistochemistry, showed a significant correlation with the PC1/3 levels obtained by qRT-PCR in assessing the increase of PC1/3 expression from SCA to CD. Twelve cases of SCA without changing their phenotype during the follow-up were used as controls: both the immunohistochemical PC1/3 expression and level of PC1/3 obtained by qRT-PCR were absent or weak in scattered neoplastic cells.
Conclusion: This study provides insight into the crucial role of the PC1/3 in the mechanism(s) of transformation of phenotype from SCA to CD
The changing faces of corticotroph cell adenomas: the role of prohormone convertase 1/3
No full textThe spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing’s disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD
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