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Background: Utilizing endoscopes in surgery offers advantages and concerns, including potential nasal function impacts. Hyposmia following Transseptal Transsphenoidal hypophysectomy ranges from 0% to 2.2%. Debates persist about managing the M.T. in endoscopic sinus surgery due to its impact on nasal function. While preservation is recommended for sinonasal health, debates continue, as certain cases require resection. Our meta-analysis aims to compare turbinate resection and preservation effects on olfactory function., Methods: We searched five electronic databases to collect all relevant studies. Records were screened for eligibility. Data were extracted from the included studies independently. Our continuous outcomes were pooled as standardized mean difference with 95% CI. Statistical analyses was done by RevMan., Results: Our meta-analysis included four studies involving 235 patients (81 males). Evaluating changes in olfaction scores, two one-month studies (82 patients) revealed no significant difference between preservation and resection groups (Std.MD = 0.05[-0.39, 0.50], p  = 0.81). For three-month assessments (146 patients), SNOT tests indicated no significant difference (Std.MD = 0.21, 95% CI[-0.11, 0.54], p  = 0.20). Two studies used other tests on 70 patients at three months, yielding no significant difference (Std.MD = 0.13, 95% CI [-0.35, 0.62], p  = 0.59). Two six-month studies (72 patients) similarly found no significant difference (Std.MD = 0.09, 95% CI [-0.39, 0.56], p  = 0.72)., Conclusion: Our meta-analysis involving 235 patients examined olfaction score changes over various time frames in trans-nasal trans-sphenoidal pituitary surgeries. No significant differences were observed between turbinate preservation and resection groups at one month, three months, or six months post-surgery.

Objective: To characterize the clinical features, neurological examination findings, diagnostic imaging results, histopathological findings, and outcome following transsphenoidal hypophysectomy (TSH) in dogs with nonfunctional sellar masses (NFSM)., Study Design: Multi-institutional retrospective study., Methods: Medical records of dogs that underwent TSH for a NFSM were reviewed for clinical signs, physical and neurological examination findings, diagnostic imaging results, endocrine testing, surgery reports, and outcome. Magnetic resonance (MR) imaging was rereviewed, and tumors were classified using the previously described system according to pituitary tumor extension and vascular involvement. Owners of dogs that survived to discharge were contacted., Results: The majority of dogs presented for mentation change (12/15). The mean pituitary to brain ratio (P/B ratio) was 1.05 (0.6-1.4). Eight dogs had a tumor imaging classification of 5B. Eleven dogs were diagnosed with a nonfunctional pituitary adenoma (NFPA). Perioperative mortality was 33% (5/15). The median survival for all dogs was 232 days (0-1658). When dogs that did not survive to discharge were excluded, the median survival time was 708 days. Seven of 10 dogs that survived the perioperative period received adjunctive therapy. Owner assessment of outcome was excellent (6/7) to good (1/7)., Conclusion: The common presenting complaint for dogs with large NFSM causing mass effect was mentation changes. Dogs with NFPA that survived to discharge and received adjunctive therapy had good to excellent outcomes., Clinical Significance: Transsphenoidal debulking with adjunctive therapy can be considered for the treatment of NFSM causing clinical signs of mass effect in dogs. Successful long-term outcomes are possible., (© 2022 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Context: Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy., Objective: This work aimed to identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment., Methods: A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology., Results: Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion., Conclusion: CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1)., Methodology: Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients' dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed., Results: A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4-37.7, p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs., Conclusions: First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term., (© 2021. The Author(s).)

Purpose: Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia., Methods: After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset., Results: Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25 days postoperatively and persisted for 5.54 days. The lowest average blood sodium level was 123.9 mEq/L, which occurred at 7.49 days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2 days post-TSS was also an independent predictor of postoperative hyponatremia onset., Conclusion: DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas., (© 2021. Italian Society of Endocrinology (SIE).)

For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey's general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.

Purpose: Intercavernous sinuses (ICSs) are physiological communications between the cavernous sinuses. The ICSs run between the endosteal and meningeal layers of the dura mater of the sella turcica. Whereas the anterior and posterior ICSs have been frequently described, the inferior ICS (iICS) has been less well studied in the literature; however, poor awareness of the ICS's anatomy can lead to serious problems during transsphenoidal, transsellar surgery. The objective of the present anatomical study was to describe the iICS in detail., Methods: The study was carried out over a 6-month period in a university hospital's anatomy laboratory, using brains extracted from human cadavers. The brains were injected with colored neoprene latex and dissected to study the iICS (presence or absence, shape, diameter, length, distance between inferior and anterior ICSs, distance between inferior and posterior ICSs, relationships, and boundaries)., Results: Seventeen cadaveric specimens were studied, and an iICS was found in all cases (100%). The shape was variously plexiform (47.1%), filiform (35.3%), or punctiform (17.6%). The mean ± standard deviation diameter and length of the iICS were 3.75 ± 2.90 mm and 11.92 ± 2.96 mm, respectively. The mean iICS-anterior ICS and iICS-posterior ICS distances were 5.36 ± 1.99 mm and 7.03 ± 2.28 mm, respectively., Conclusion: The iICS has been poorly described in the literature. However, damage to the iICS during transsphenoidal, transsellar surgery could lead to serious vascular complications. A precise radiological assessment appears to be essential for a safe surgical approach.

Importance: Iatrogenic olfactory dysfunction after endoscopic transsphenoidal hypophysectomy (ETSH) is an overlooked complication without elucidated risk factors., Objective: To assess the independent prognostic role of demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative parameters in patient-reported postoperative olfactory dysfunction, and to explore the association between anatomical measurements of the skull base and sinonasal cavity and postoperative olfactory dysfunction., Design, Setting, and Participants: This retrospective cohort study in a tertiary care medical center enrolled consecutive patients with primary sellar lesions who underwent ETSH between January 1, 2015, and January 31, 2019. Patients were excluded if they underwent multiple sinonasal surgical procedures, presented with a sellar malignant neoplasm, required an expanded transsphenoidal approach, had nasal polyposis or a neurodegenerative disease, or sustained traumatic brain injury. After undergoing medical record review and telephone screening, patients were asked to participate in a 3-item telephone survey., Main Outcomes and Measures: The primary outcome was the Clinical Global Impressions change in smell rating, a validated transitional patient-reported outcome measure. Patients rated their change in smell before and after ETSH on a 7-point Likert scale, with the following response options: (1) much better, (2) somewhat better, (3) slightly better, (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, or (7) much worse. Responses of slightly worse, somewhat worse, and much worse were surrogates for postoperative olfactory dysfunction status. Patient medical records, preoperative imaging scans, operative notes, and pathology reports were reviewed., Results: Of the 147 patients (mean [SD] age, 54 [15] years; 79 women [54%]) who responded to the telephone survey, 42 (29%) reported olfactory dysfunction after ETSH. Median (interquartile range [IQR]) time between the ETSH completion and survey response was 31.1 (21-43) months. On multivariable analysis, abdominal fat grafting (adjusted relative risk [aRR], 2.95; 95% CI, 1.89-4.60) was associated with postoperative olfactory dysfunction, whereas smoking history (aRR, 1.54; 95% CI, 0.95-2.51) demonstrated a clinically meaningful but imprecise effect size. A more obtuse angle between the planum sphenoidale and face of the sella turcica on sagittal imaging was protective (aRR, 0.98; 95% CI, 0.96-0.99). Increased number of months after the ETSH was associated with patient-reported normosmia (aRR, 0.93; 95% CI, 0.91-0.95). In contrast, other comorbidities; intraoperative variables such as turbinate resection, nasoseptal flap, and mucosal or bone grafting; histological variables such as pathology and proliferative index; and postoperative variables such as adjuvant radiotherapy were not associated with postoperative olfactory dysfunction., Conclusions and Relevance: This study found that abdominal fat grafting, acute skull base angle, and smoking history appeared to be clinically significant risk factors for patient-reported postoperative olfactory dysfunction. Increased time after ETSH may be associated with better olfactory outcomes.

A 57-year-old woman presented with severe lethargy, dizziness and nausea 1 week after transsphenoidal resection of a growth hormone secreting pituitary adenoma. She was found to have severe hyponatremia of 115 mmol/L. Importantly, she was neurologically intact and clinically euvolaemic. Her fluid intake was restricted and her sodium levels increased to 131 mmol/L over 4 days. She made a full recovery.She was diagnosed with isolated second-phase diabetes insipidus, a state of symptomatic hypoosmolar hyponatremia that usually occurs 7-10 days after transsphenoidal surgery. The sodium levels improve with fluid restriction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Recombinant human growth hormone (rhGH) replacement therapy is often prescribed in patients with nonfunctioning pituitary adenoma (NFPA) or craniopharyngioma., Objective: To study whether rhGH therapy in patients with adult growth hormone deficiency (AGHD) increases the risk of pituitary tumor recurrence., Design: Retrospective, observational study., Setting: Tertiary care center., Patients: We studied 283 consecutive patients with AGHD due to NFPA or craniopharyngioma between 1995 and 2018., Intervention: rhGH treatment at standard doses was initiated in 123 patients (43.5%). The remaining 160 patients served as controls., Main Outcome Measure: Risk of tumor recurrence in rhGH-treated and control patients., Results: In univariate analysis, recurrence of the pituitary tumor was less frequent in rhGH-treated patients (19.5%) than in controls (29.7%; hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.32-0.86; P = .01). Multivariate Cox analysis demonstrated that the risk of tumor recurrence was associated with detection of residual disease at the baseline magnetic resonance imaging (HR 9.17; 95% CI, 4.88-17.22; P < .001) and not having performed radiotherapy (HR 16.97; 95% CI, 7.55-38.16; P < .001), while rhGH treatment was no longer associated with a lower risk of recurrence (HR 0.82; 95% CI, 0.47-1.44; P = .50)., Conclusions: We found no association between rhGH replacement and the risk of tumor recurrence in patients with AGHD caused by NFPA or craniopharyngioma. These data add to the mounting evidence that rhGH therapy has a neutral effect on the recurrence of pituitary tumors., Précis: Replacement therapy with rhGH is prescribed to patients with adult growth hormone deficiency. Our study found no increased risk of pituitary tumor recurrence., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There remains considerable variation in the extent of sinonasal preservation during the approach for endoscopic transsphenoidal hypophysectomy (TSH). We advocate for a minimally destructive approach utilizing turbinate lateralization, small posterior septectomy, no ethmoidectomy, and preservation of nasoseptal flap (NSF) pedicles bilaterally. Due to these factors, this approach may affect the rates of postoperative rhinosinusitis. The objective of this study is to define the rates of postoperative rhinosinusitis in patients undergoing this approach., Methods: Single institution, retrospective chart review of patients undergoing TSH from 2005 to 2018., Results: A total of 415 patients were identified and 14% developed an episode of postoperative rhinosinusitis within 3 months. These patients were significantly more likely to have had a history of recurrent acute or chronic rhinosinusitis. Most cases were sphenoethmoidal sinusitis managed with 1 to 2 courses of antibiotics. Of patients with postoperative rhinosinusitis, most did not undergo NSF. Average follow-up was 38 months. Six patients (1.4%) underwent post-TSH functional endoscopic sinus surgery (FESS). Average time from TSH to FESS was 26.3 months. Two of these patients had a history of prior chronic rhinosinusitis without polyposis. Two patients underwent revision TSH for recurrent tumor as the primary indication for surgery at time of FESS. Twenty-two-item Sino-Nasal Outcome Test (SNOT-22) scores generally increased immediately postoperatively, but frequently decreased below preoperative level by the time of last follow-up, regardless of whether patients developed rhinosinusitis., Conclusion: Sinonasal preservation during TSH is associated with a low rate of postoperative rhinosinusitis requiring FESS and excellent long-term patient reported outcomes. We continue to advocate for sinonasal preservation during pituitary surgery., (© 2019 ARS-AAOA, LLC.)

Context: The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas., Objective: To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients., Methods: Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses., Results: A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results., Conclusions: In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists., (© Endocrine Society 2019.)

Introduction: Transsphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0,5-15% in the main published series., Objectives: The primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication., Methods: The data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed., Results and Conclusions: The incidence of postoperative CSF leakage in our series was 2,3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumors with suprasellar extension (P<.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (P<.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development., (Copyright © 2019 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: The aim of this study was to describe the anaesthetic management and perianaesthetic complications encountered during hypophysectomy surgery in acromegalic cats. We explored relationships between animal demographic data, the anaesthetic protocol used and presence of perioperative complications., Methods: Cats having undergone hypophysectomy surgery for the treatment of feline acromegaly at a single veterinary referral hospital were identified from hospital records. The anaesthesia records and clinical notes of these animals were retrospectively reviewed. Descriptive statistics were produced and binary logistic regression run to assess for any relationship between patient factors, anaesthetic management and complications during the perioperative period., Results: Perianaesthetic complications identified included hypothermia, hypotension, bradycardia and airway obstruction. Mortality at 24 h post-anaesthesia was 8%. The use of alpha (α) 2 agonists was associated with a lower incidence of hypotension. Fentanyl infusion was associated with a higher incidence of airway obstruction compared with remifentanil. Subjectively assessed anaesthetic recovery quality had an association with the number of days spent in the intensive care ward postoperatively., Conclusions and Relevance: The anaesthetic management described seems effective for hypophysectomy surgery in cats. Intraoperative complications were common and, while not apparently associated with 24 h patient outcome, drugs and equipment to manage these complications should be available.

Background: Combined central diabetes insipidus and cerebral salt wasting syndrome is a rare clinical finding. However, when this happens, mortality is high due to delayed diagnosis and/or inadequate treatment., Case Presentation: A 42-year-old white man was referred to neurosurgery due to a non-functional pituitary macroadenoma. He underwent a partial resection of the tumor on July 2, 2015. On the day following surgery he presented polyuria with sodium 149 mEq/L, plasma osmolality 301 mOsm/kg, and urine osmolality 293 mOsm/kg. He started nasal desmopressin 0.05 mg/day with good response. He was already on dexamethasone 4 mg and levothyroxine 75 mcg due to hypopituitarism after surgery. On July 9 he became confused. Cerebral computed tomography was performed with no significant changes. His natremia dropped to 128 mEq/L with development of polyuria despite maintenance of desmopressin dose. His hemoglobin and hematocrit rose from 9.1 g/L to 11.6 g/L and 27.5 to 32.5, respectively. His thyroid function was normal and he was on hydrocortisone 30 mg/day. At 12 p.m. 150 mg/hydrocortisone infusion was initiated, but sodium did not increase. Plasma and urine osmolality were 264 mOsm/kg and 679 mOsm/kg, respectively. At 4 p.m. hydrocortisone was increased and hypertonic saline replacement started. Two hours later he was dehydrated with polyuria and vomiting, and natremia of 124 mEq/L. Hyponatremia was very resistant to treatment despite hypertonic saline replacement, hence desmopressin was suspended. The following day, urine spot analysis showed that natriuresis was 63 mEq/L with serum sodium 132 mEq/L. This was interpreted as a cerebral salt wasting syndrome and control was achieved with aggressive hypertonic saline replacements and fludrocortisone 0.1 mg/three times a day., Conclusions: We present a rare case of a patient with diabetes insipidus and cerebral salt wasting syndrome, who was successfully treated. Hyponatremia in a patient with diabetes insipidus may erroneously be interpreted as inadequate diabetes insipidus control or as syndrome of inappropriate antidiuretic hormone secretion, leading to therapeutic errors. Thus, all clinical and analytical data should be evaluated together for early and correct diagnosis.

Objective: Pituitary abscess (PA) is a rare but serious intrasellar disorder with potentially high disability and mortality. Secondary PA after transsphenoidal surgery (TS) is extremely rare, and only a few case reports have been identified in the literature. This study explored the salient clinical manifestations and etiologies to determine appropriate treatment., Methods: A retrospective review of 6832 consecutive patients who had undergone TS for pituitary diseases in Peking Union Medical College Hospital between 2003 and 2017 was performed. Demographics, previous medical and surgical history, clinical presentation, imaging features, and treatment details of 23 patients who had been diagnosed with secondary PA after TS among the cohort were reviewed., Results: Among these patients, the original pituitary lesion before TS included Rathke's cleft cyst (8 patients, 34.8%), nonfunctioning pituitary adenoma (11 patients, 47.8%), and somatotropic adenoma (4 patients, 17.4%). The diameter of the original pituitary lesion ranged from 11 to 47 mm. About 52% of secondary PAs occurred within a half a year after surgery. Based on the history of TS, clinical presentation, biochemical testing, and typical imaging features, the preoperative diagnosis rate was as high as 78%., Conclusions: Although rare, secondary PA should be included in the differential diagnosis of intrasellar lesions after TS. Patients with an initial diagnosis of Rathke's cleft cyst or pituitary macroadenoma were more likely to have PA after TS. Adequate surgical drainage combined with microbiology-guided antibiotic therapy is the first choice for treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Patients undergoing transsphenoidal pituitary surgery (TSS) are at risk for several serious complications, including the syndrome of inappropriate antidiuretic hormone and subsequent hyponatremia., Objective: In this study, we examined the effect of 1 week of post-discharge fluid restriction to 1.0 L daily on rates of post-operative readmission for hyponatremia., Methods: We retrospectively analyzed all patients undergoing TSS from 2008 to 2014 and prospectively recorded patient data from 2015 to 2017. Patients were divided into a control cohort (2008-2014), who were discharged with instructions to drink to thirst; and an intervention cohort (2015-2017) who were instructed to drink less than 1.0 L daily for 1 week post-operatively., Results: This study included 788 patients; 585 (74.2%) in the control cohort and 203 (25.8%) in the intervention cohort. Overall, 436 (55.3%) were women, the median age was 47 (range 15-89), and average BMI was 29.4 kg/m 2 (range 17.7-101.7). Patients were relatively well matched. Of patients in the intervention group, none was readmitted for hyponatremia (0/203), compared to 3.41% (20/585) in the control group (p = 0.003). Patients in the intervention group also had significantly higher post-operative week one sodium levels (140.1 vs 137.5 mEq/L; p = 0.002). No fluid balance complications occurred in patients who followed this protocol., Conclusion: Hyponatremia can be a life-threatening complication of TSS, and prevention of readmission for hyponatremia can help improve patient safety and decrease costs. Mandatory post-discharge fluid restriction is a simple and inexpensive intervention associated with decreased rates of readmission for hyponatremia and normal post-operative sodium levels.

Purpose: Silent corticotroph adenomas (SCAs) are clinically silent and non-secreting, but exhibit positive adrenocorticotropic hormone (ACTH) immunostaining. We characterized a single center cohort of SCA patients, compared the SCAs to silent gonadotroph adenomas (SGAs), identified predictors of recurrence, and reviewed and compared the cohort to previously published SCAs cases., Methods: Retrospective review of SCA and SGA surgically resected patients over 10 years and 6 years, respectively. Definitions; SCA-no clinical or biochemical evidence of Cushing's syndrome and ACTH positive immunostaining, and SGA-steroidogenic factor (SF-1) positive immunostaining. A systematic literature search was undertaken using Pubmed and Scopus., Results: Review revealed 814 pituitary surgeries, 39 (4.8%) were SCAs. Mean follow-up was 6.4 years (range 0.5-23.8 years). Pre-operative magnetic resonance imaging demonstrated sphenoid and/or cavernous sinus invasion in 44%, 33% were > 50% cystic, and 28% had high ACTH levels pre-operatively. Compared to SGAs (n = 70), SCAs were of similar size and invasiveness (2.5 vs. 2.9 cm, p = 0.2; 44 vs. 41%, p = 0.8, respectively), but recurrence rate was higher (36 vs. 10%, p = 0.001) and more patients received radiation therapy (18 vs. 3%, p = 0.006). Less cystic tumors (0 vs. 50%, p < 0.001) and higher pre-operative ACTH levels (54 vs. 28 pg/ml, p = 0.04) were predictors of recurrence for SCAs., Conclusion: This review is unique; a strict definition of SCA was used, and single center SCAs were compared with SGAs and with SCAs literature reviewed cases. We show that SCAs are aggressive and identify predictors of recurrence. Accurate initial diagnosis, close imaging and biochemical follow up are warranted.

Purpose: Remission from Cushing disease (CD) after pituitary adenoma resection may be predicted by a postoperative reduction in serum cortisol level. A 2008 consensus statement recommends assessing morning cortisol levels during the first postoperative week, and replacing glucocorticoid (GC) if cortisol nadir of < 2 or < 5 µg/dL is achieved. We sought to evaluate adherence to consensus recommendations following adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma resection at our tertiary medical center, and assess time to cortisol nadir to better define the window for assessment and intervention., Methods: We retrospectively analyzed data extracted from in-hospital electronic medical records for CD surgeries between January 1991 and September 2015. We compared cortisol levels and collection times, ACTH measurement, and postoperative and discharge GC treatment before and after consensus statement publication in July 2008., Results: 107 surgeries were performed in 92 patients with CD. After 2008, more surgeries had at least one cortisol value assessed (67.9% before vs. 91.3% after, p = 0.033), with median initial cortisol measurement at 14 h post-surgery. However, ACTH measurement remained unchanged (42.9% vs. 43.5%; p > 0.99). Cortisol collection during GC treatment tended to increase (32.7% vs. 57.1%; p = 0.068). Of surgeries performed without prior GC treatment, 31.7 and 55.0% had a cortisol nadir of < 2 and < 5 µg/dL, respectively, within 72 h postoperative., Conclusions: Our physicians were more diligent in measuring in-hospital postoperative cortisol levels consistent with 2008 consensus recommendations. Better management of cortisol measurements and their timing is an opportunity for improvement.

Objectives: To determine if the consistency of pituitary adenomas can be predicted based on a preoperative MRI study and to assess the surgical outcome of firm pituitary adenomas., Materials and Methods: One hundred consecutive patients with pituitary adenomas and suprasellar extension were operated by a transsphenoidal approach from July 2003 to December 2006. In addition to the neurological examination, the patients were evaluated by ophthalmological, endocrinological and radiological workups. The signal intensity of the lesion on T2WI and other dimensions of the tumors were included in the MRI study., Results: There were 52 male and 48 female patients with a mean age of 42.47 years. The mean diameter of the tumor was 32.97mm and the mean SSE was 14.95mm. Six out of 100 patients had firm adenomas peroperatively. Only one of the six patients had isointense SI on T2 WI. Of these 6 patients, total excision was performed in 1 patient, subtotal in 3 patients and partial excision in 2 patients. Among the six patients with firm adenomas, 4 had preoperative hypopituitarism (P<0.001). There was a statistically significant correlation between consistency and the postoperative permanent hypopituitarism (P<0.001). The average follow up was 43.5 months. The literature is reviewed and various aspects of pituitary adenoma consistency are discussed., Conclusions: With the present study, the consistency of pituitary adenomas cannot be reliably predicted based on a preoperative MRI study. Patients with firm adenomas likely to have more incidence of preoperative hypopituitarism and postoperative permanent hypopituitarism., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Clinically non-functioning pituitary adenomas (NFPAs) are among the most common tumors in the sellar region. These lesions do not cause a hormonal hypersecretion syndrome, and are therefore found incidentally (particularly microadenomas) or diagnosed based on compressive symptoms such as headache and visual field defects, as well as clinical signs of pituitary hormone deficiencies. Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or their subunits and are therefore called gonadotropinomas, while 30% of them show no immunostaining for any hormone and are known as null cell adenomas. The diagnostic approach to NFPAs should include visual field examination, an assessment of the integrity of all anterior pituitary hormone systems, and magnetic resonance imaging of the sellar region to define tumor size and extension. The treatment of choice is transsphenoidal resection of the adenoma, which in many instances cannot be completely accomplished. The recurrence rate after surgery may be up to 30%. Persistent or recurrent adenomas are usually treated with radiation therapy. In a small proportion of these cases, drug treatment with dopamine agonists and, to a lesser extent, somatostatin analogs may achieve reduction or at least stabilization of the tumor., (Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.)

In patients undergoing endoscopic transsphenoidal hypophysectomy, the nasal mucosa is often infiltrated with local anesthetic solutions that contain epinephrine to aid hemostasis. This may, however, result in hemodynamic changes, especially hypotension. We characterized the cardiovascular changes using a LiDCOrapid monitor in 13 patients after the infiltration of 4% articaine containing 1:200,000 epinephrine. Nine (69%) had a >20% decrease in mean arterial pressure at a median time of 116 seconds after the infiltration of articaine with epinephrine. Analysis of the cardiac output data revealed that this was caused by a sustained reduction in systemic vascular resistance. The arterial blood pressure normalized over a period of 60 to 90 seconds secondary to increases in stroke volume and heart rate producing an elevation in cardiac output. Transient hypotension following the infiltration of epinephrine-containing local anesthetics may be caused by epinephrine stimulation of β2-adrenoceptors producing vasodilation.

Aim: Major complications of microscopic transnasal hypophyseal surgery (MTHS), such as cerebrospinal fluid rhinorrhea, carotid injury, and optic nerve injury, are very rare. However, late rhinological complications can be ignored because they are a minor cause of morbidity compared with major complications. In this study, we extensively examined postoperative rhinological complications in patients who underwent MTHS for pituitary adenoma., Material and Methods: Thirty-one patients diagnosed with pituitary adenoma, who underwent MTHS and whose preoperative nasal examinations were recorded between January 2007 and January 2014, were included in the study. A detailed rhinological examination of the patients was performed., Results: A total of 12 of 31 patients (38.7%) had a perforated nasal septum, and synechiae were detected in the nasal cavities of 13 patients (42%). Anosmia occurred in three patients, hyposmia in two, and a nasal tip deflection and saddle nose deformity were detected in one patient with a perforated nasal septum. No perinasal loss of sense, oronasal fistula, or purulent secretion in the nasal cavity was found in any patient., Conclusion: The nasal structures, particularly the nasal septum mucosa, should be treated gently during MTHS. The nasal stages of the operation should be performed with the help of an otolaryngologist until adequate experience is gained.

Introduction: The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery., Methods and Result: A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later., Conclusion: If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Total hypophysectomy it is a classical procedure that currently has many indications especially in patients with Cushing syndrome without good endocrine control. Expanded endonasal endoscopic techniques grant us an alternative standpoint to the classic trans-sphenoidal microscopic approach and a comprehensive assessment of the process METHOD: The author provides technical nuances and describe step by step the radical endoscopic hypophysectomy. The study of cadaveric specimens adds clarifying dissections., Conclusions: Radical hypophysectomy is an easily replicable and safe procedure. The most important morbidity is the intraoperative cerebrospinal fluid (CSF) leakage, which is inherent to this technique and can be successfully prevented with a pedicled nasoseptal flap reconstruction.

Context: Acromegaly is a systemic disorder caused by a GH-secreting pituitary adenoma. As with other rare diseases, acromegaly registries developed in various European countries have provided us with important information., Objective: The objective of the study was to analyze the epidemiological, clinical, biochemical, and therapeutic data from the Mexican Acromegaly Registry (MAR)., Setting: The setting of the study was a nationwide patient registry., Design and Methodology: The MAR was created in 2009. It gathers data from 24 participating centers belonging to three different institutions using a specifically designed on-line platform. Only patients diagnosed after 1990 were included in the program., Results: A total of 2057 patients (51% female, mean age at diagnosis 41.1 ± 24.5 y) have been registered for an estimated prevalence of 18 cases per 1 million inhabitants. Hypertension, glucose intolerance, diabetes, and dyslipidemia were present in 27%, 18.4%, 30%, and 24% of the patients, respectively. The IGF-1 level at diagnosis and the concomitant presence of hypertension were significantly associated with the development of diabetes. Transsphenoidal surgery was the primary treatment in 72% of the patients. Pharmacological treatment, mostly with somatostatin analogs, was administered primarily and adjunctively in 26% and 54% of the patients, respectively. Treatment choice varied among the three participating institutions, with the predominance of pharmacological therapy in two of them and of radiation therapy in the third. Therapeutic outcomes were similar to those reported in the European registries., Conclusions: The MAR is the largest and first non-European registry of the disease. Our findings highlight important within-country differences in treatment choice due to variations in the availability of resources.

Cerebral vasospasm following transsphenoidal hypophysectomy is an exceedingly rare but serious complication with high morbidity and mortality. The initial signs and symptoms of cerebral vasospasm following transsphenoidal hypophysectomy are changes in mental status, motor deficits, and speech difficulties. Symptomatic vasospasm is difficult to reverse despite treatment and often only resolves with time. Furthermore, most transsphenoidal hypophysectomy patients have been discharged before the onset of vasospasm, so when they do present it is often in a fulminant form and recalcitrant to available treatments.All previously reported patients of cerebral vasospasm following transsphenoidal hypophysectomy were status postresection of a pituitary macroadenoma. The authors report the first patient of vasospasm following transsphenoidal hypophysectomy in the treatment of lymphocytic hypophysitis; a rare inflammatory disorder characterized by lymphocytic infiltration of the pituitary gland causing destruction glandular tissue.

Purpose: Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications., Methods: We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27-61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2-4.2 mIU/L), with median fT4 2.52 ng/dL (0.9-1.7 ng/dL)., Results: Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease -72%), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach., Conclusions: Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50%). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.

Purpose: To compare hypothalamus-pituitary-adrenal (HPA) axis integrity at diagnosis and recovery after transsphenoidal surgery (TSS), in acromegaly patients, compared with tumor size matched non-functioning adenoma (NFA) patients., Methods: A retrospective 7-year evaluation of acromegaly patients, who underwent TSS with 52 weeks follow-up at a single institution, was undertaken. 50 acromegaly with complete follow-up data at all points and 50 NFA patients were matched for tumor size; HPA axis was similarly assessed pre-operatively and at 6, 12 and 52 weeks post-operatively. Recovery of HPA axis and gender specific prevalence of adrenal insufficiency (AI), were analyzed in both groups. We also studied AI in acromegaly patients requiring medical therapy post-operatively vs those in remission after surgery., Results: AI remained less prevalent in acromegaly vs NFA (acromegaly, p = 0.01; NFA, p = 0.15) at 52 weeks after surgery, although the prevalence of AI decreased in both groups from baseline by 52 weeks. Additionally, recovery from baseline AI was significantly greater by 52 weeks in acromegaly patients over NFA patients (p = 0.001). Recovery of HPA axis in acromegaly patients remained significant (p = 0.03) despite the need for medical therapy. AI at baseline was proportionately more prevalent in acromegalic males at baseline (p = 0.002) but no gender difference was apparent at 52 weeks (p = 0.35). Conversely, in NFA patients, no gender difference was apparent pre-operatively (p = 0.49), but AI was more prevalent in males at 52 weeks (p = 0.001)., Conclusion: In the longest comparative study to date using a standard assessment modality, HPA axis recovery was more frequent in acromegaly compared to NFA patients, independent of tumor size, cavernous sinus invasion (CSI), and body mass index (BMI). HPA axis integrity must be carefully and periodically monitored in acromegaly patients during short- and long-term follow-up to prevent overtreatment with glucocorticoids.

Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome.

Fluid and electrolyte imbalances are the most frequent complications following pituitary surgery. Among the several patterns of occurrence, hyponatremia can occur in an isolated fashion or as part of a bi- or triphasic pattern. The frequency of hyponatremia after trans-sphenoidal surgery is between 2% and 25%, according to the literature. However, these numbers are probably underestimating the real prevalence, since mild hyponatremia does not lead to symptoms and measurement of sodium level. No association has been described between entity of the pituitary tumor or tumor size and hyponatremia. Therefore no predictors exist to determine patients with a higher risk for electrolyte imbalances after surgery. However, since delayed hyponatremia occurs mainly around the 8-10th day after surgery, routine measurement of sodium should be recommended on the day of hospital dismission. In case of a symptomatic hyponatremia, insufficiency of the corticotrophe pituitary function as the leading differential diagnosis needs to be ruled out. If the patient is euvoleme, pretest probability of syndrome of inadequate antidiuretic hormone production (SIADH) is very high and therapy may be started according to this. In case of SIADH, therapeutic options include fluid restriction or vaptane therapy. Only in severe cases infusion of hypertonic saline is appropriate. Usually SIADH following pituitary surgery is a self-limiting condition and will cease within 2-5 days.

A 61-year-old woman developed bilateral decreased vision within 30 hours of uncomplicated trans-sphenoidal pituitary adenoma resection. Postoperative computed tomography of the brain was consistent with overpacking of the sella turcica with a fat graft. The patient was urgently taken back to the operating room for fat graft reduction and her vision improved., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Fifteen years ago orexins were identified as central regulators of energy homeostasis. Since then, that concept has evolved considerably and orexins are currently considered, besides orexigenic neuropeptides, key modulators of sleep-wake cycle and neuroendocrine function. Little is known, however, about the effect of the neuroendocrine milieu on orexins' effects on energy balance. We therefore investigated whether hypothalamic-pituitary axes have a role in the central orexigenic action of orexin A (OX-A) by centrally injecting hypophysectomized, adrenalectomized, gonadectomized (male and female), hypothyroid, and GH-deficient dwarf rats with OX-A. Our data showed that the orexigenic effect of OX-A is fully maintained in adrenalectomized and gonadectomized (females and males) rats, slightly reduced in hypothyroid rats, and totally abolished in hypophysectomized and dwarf rats when compared with their respective vehicle-treated controls. Of note, loss of the OX-A effect on feeding was associated with a blunted OX-A-induced increase in the expression of either neuropeptide Y or its putative regulator, the transcription factor cAMP response-element binding protein, as well as its phosphorylated form, in the arcuate nucleus of the hypothalamus of hypophysectomized and dwarf rats. Overall, this evidence suggests that the orexigenic action of OX-A depends on an intact GH axis and that this neuroendocrine feedback loop may be of interest in the understanding of orexins action on energy balance and GH deficiency.

Objective: Acromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality., Design and Methods: The mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis., Results: Twenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43-1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (P=0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06-28.77, P=0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56-309.04, P=0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease., Conclusions: Therapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients.

Introduction: Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS)., Design: Retrospective comparative matched case-control study., Patients & Methods: 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated., Results: Compared to matched controls ACT patients had higher HbA1c levels (6.9±1.4 vs. 5.5±0.7% (p<0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2% (p=0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89±9 vs. 79±11 mmHg (p=0.001), prevalence of LVH (41.7 vs. 1.7% (p<0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0% (p=0.03)), higher HbA1c levels (6.8±1.3 vs. 5.5±0.7% (p=0.0005)) and a higher FS (21.2±9.7 vs. 12.4±7.7% (p=0.002), OR 1.11 [1.02-1.21] (p=0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1% (p<0.0001)) and HbA1c levels (6.4±1.2 vs. 5.5±0.8% (p=0.006)) were found compared to controls., Conclusion: When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: For secondary adrenal insufficiency (SAI), established biochemical parameters for dosage control are lacking and no optimal substitution dosage and daily distribution have been determined yet. Therefore, in clinical practice, the individual total dose is often adjusted based on patients' subjective well-being., Design: Effects of three standard glucocorticoid replacement regimens on psychological variables were assessed in patients with SAI based on a randomized double-blind study design., Methods: SAI patients (n=18) were treated with three different established glucocorticoid replacement regimens in a randomized, double-blind, crossover study (treatment A, hydrocortisone 10 mg-placebo-5 mg-placebo; treatment B, hydrocortisone 10 mg-5 mg-placebo-5 mg; and treatment C, prednisone 5 mg-placebo-placebo-placebo). Following each 4-week replacement regimen, quality of life (SF-36) and emotional distress (brief symptom inventory (BSI)) were assessed along with diurnal changes in current well-being (Bf-S) and alertness (Stanford Sleepiness Scale (SSS)) using validated questionnaires, and additionally compared with patient (patients with pituitary disease and adrenal sufficiency) and healthy control groups., Results: SAI patients showed improvements in physical quality of life (i.e. SF-36 physical function, P<0.05; physical role function, P<0.05) and current well-being (at 1800 h, P<0.05) under treatment A (hydrocortisone 10-0-5-0 mg) compared with the other replacement regimens. Quality of life and current well-being were significantly impaired compared with healthy controls but did not differ from patient controls., Conclusions: Although the observed improvements in psychological parameters were comparatively small, our results indicate beneficial effects of a 10-0-5-0 mg hydrocortisone replacement regimen. Nevertheless, treatment effects were insufficient to restore subjective health compared with healthy controls, indicating the need for improved replacement regimens and supportive psychosocial interventions in SAI patients.

Both stiffness and strength of bones are thought to be controlled by the "bone mechanostat". Its natural stimuli would be the strains of bone tissue (sensed by osteocytes) that are induced by both gravitational forces (body weight) and contraction of regional muscles. Body weight and muscle mass increase with age. Biomechanical performance of load-bearing bones must adapt to these growth-induced changes. Hypophysectomy in the rat slows the rate of body growth. With time, a great difference in body size is established between a hypophysectomized rat and its age-matched control, which makes it difficult to establish the real effect of pituitary ablation on bone biomechanics. The purpose of the present investigation was to compare mid-shaft femoral mechanical properties between hypophysectomized and weight-matched normal rats, which will show similar sizes and thus will be exposed to similar habitual loads. Two groups of 10 female rats each (H and C) were established. H rats were 12-month-old that had been hypophysectomized 11 months before. C rats were 2.5-month-old normals. Right femur mechanical properties were tested in 3-point bending. Structural (load-bearing capacity and stiffness), geometric (cross-sectional area, cortical sectional area, and moment of inertia), and material (modulus of elasticity and maximum elastic stress) properties were evaluated. The left femur was ashed for calcium content. Comparisons between parameters were performed by the Student's t test. Average body weight, body length, femur weight, femur length, and gastrocnemius weight were not significantly different between H and C rats. Calcium content in ashes was significantly higher in H than in C rats. Cross-sectional area, medullary area, and cross-sectional moment of inertia were higher in C rats, whereas cortical area did not differ between groups. Structural properties (diaphyseal stiffness, elastic limit, and load at fracture) were about four times higher in hypophysectomized rats, as were the bone material stiffness or Young's modulus and the maximal elastic stress (about 7×). The femur obtained from a middle-aged H rat was stronger and stiffer than the femur obtained from a young-adult C rat, both specimens showing similar size and bone mass and almost equal geometric properties. The higher than normal structural properties shown by the hypophysectomized femur were entirely due to changes in the intrinsic properties of the bone; it was thus stronger at the tissue level. The change of the femoral bone tissue was associated with a high mineral content and an unusual high modulus of elasticity and was probably due to a diminished bone and collagen turnover.

Introduction: Endoscopic, transnasal management of pituitary gland neoplasms is a widely accepted alternative to the traditional microscopic approach. This study aimed to determine outcomes and complication rates for the largest UK series of endoscopic, trans-sphenoidal hypophysectomies reported to date., Methods: We performed a retrospective analysis of 136 primary resections and 35 revision cases performed at a tertiary referral centre., Results and Analysis: Total tumour resection was confirmed in over 85 per cent of primary and revision cases, with biochemical remission in 60 per cent. The incidence of complications such as epistaxis, sphenoid sinus problems, endocrine insufficiency, visual disturbance, post-operative haemorrhage, cranial nerve injury and mortality was significantly lower, compared with similar series using the microscopic approach., Conclusion: Despite its steep 'learning curve', our series demonstrates that the endoscopic approach not only allows superior anatomical visualisation and therefore facilitates full oncological resection of tumours, but also reduces the incidence of peri-operative complications.

Object: Craniopharyngiomas are benign tumors but their close anatomical relationship with critical neurological, endocrine, and vascular structures makes gross-total resection (GTR) with minimal morbidity difficult to achieve. Currently, there is controversy regarding the extent, timing, and modality of treatment for pediatric craniopharyngioma., Methods: The authors performed a systematic review of the published literature on pediatric craniopharyngioma to determine patterns of clinical practice and the reported outcomes of standard treatment strategies. This yielded 109 studies, which contained data describing extent of resection for a total of 531 patients. Differences in outcome were examined based upon extent of resection and choice of radiation treatment., Results: Gross-total resection was associated with increased rates of new endocrine dysfunction (OR 5.4, p < 0.001), panhypopituitarism (OR 7.8, p = 0.006), and new neurological deficits (OR 9.9, p = 0.03) compared with biopsy procedures. Subtotal resection (STR) was not associated with an increased rate of new neurological deficits. Gross-total was associated with increased rates of diabetes insipidus (OR 7.7, p = 0.05) compared with the combination of STR and radiotherapy (RT). The addition of RT to STR was associated with increased rates of panhypopituitarism (OR 9.9, p = 0.01) but otherwise similar rates of morbidities., Conclusions: Although subject to the limitations of a literature review, this report suggests that GTR is associated with increased rates of endocrinopathies compared with STR + RT, and this should be considered when planning goals of surgery.

Sleep is characterized by a reduced response to external stimuli and a particular form of electroencephalographic (EEG) activity. Sleep is divided into two stages: REM sleep, characterized by muscle atonia, rapid eye movements, and EEG activity similar to wakefulness, and non-REM sleep, characterized by slow EEG activity. Around 80% of total sleep time is non-REM. Although it has been intensely studied for decades, the function (or functions) of sleep remains elusive. Sleep is a highly regulated state; some brain regions and several hormones and cytokines participate in sleep regulation. This mini-review focuses on how pituitary hormones and cytokines regulate or affect sleep and how sleep modifies the plasma concentration of hormones as well as cytokines. Also, we review the effects of hypophysectomy and some autoimmune diseases on sleep pattern. Finally, we propose that one of the functions of sleep is to maintain the integrity of the neuro-immune-endocrine system., (© 2012 New York Academy of Sciences.)

We report here a rare case of a young male patient presenting with a Multiple Endocrine Neoplasia Type 1 - prolactin-secreting pituitary carcinoma, controlled long-term after temozolomide withdrawal. Initial presentation was pituitary apoplexy leading to surgery. Dopamine agonists and radiotherapy allowed control of prolactin secretion and pituitary remnant. Metastasis appeared 10 years after initial presentation, leading to the diagnosis of pituitary carcinoma. At that time, dopamine agonists were no more effective; temozolomide, an oral alkylating agent, was administered for 24 cycles, and allowed decrease of the volume of the pituitary lesion and metastases. The patient is still currently followed in our department, 3 years after temozolomide withdrawal: prolactin level and pituitary tumor volume remain controlled without any chemotherapy. To our knowledge, this is the first case of MEN1 prolactin secreting pituitary carcinoma controlled long-term after temozolomide discontinuation., (Copyright © 2012. Published by Elsevier Masson SAS.)

Transsphenoidal surgery is the mainstream in the management of sellar and anterior fossa diseases. However, textiloma, as known as cotton left behind during an operation, is rarely reported as a complication of transsphenoidal surgery. In this paper, we present a case of textiloma after transsphenoidal surgery. The patient had been suffering progressive blurred vision and she received transsphenoidal surgery for the diagnosis of pituitary tumor. However, the intermittent headaches persisted for half a year after the surgery. The subsequent images revealed a rim-like enhanced tumor in the sellar region. The retained cotton material was found when she underwent transcranial surgery. The etiology and management of textiloma are discussed, and the relevant literature also reviewed.