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- The infundibulo-tuberal syndrome caused by craniopharyngiomas: clinicopathological evidence from an historical French cohort (1705-1973). [JOURNAL ARTICLE]
- Pituitary 2014 Dec 20.
Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs).A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era.Three major syndromes caused by CPs were categorized: pituitary syndrome (35 %), infundibulo-tuberal syndrome (52 %) and hypothalamic syndrome (49 %). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82 %). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001).This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.
- Current status on histological classification in Cushing's disease. [JOURNAL ARTICLE]
- Pituitary 2014 Dec 14.
Managing Cushing's disease remains a challenge. Surgery is the first option of treatment and it offers a high success rate. Even in cases where biochemical remission is not achieved, it is crucial to obtain surgical tissue for morphological diagnosis because the therapeutic approach can be modified according to the findings.A literature search was performed using PubMed for information regarding pathology and Cushing's disease.The histopathological features found in the pituitary gland of patients with Cushing's disease are presented.Different subtypes of ACTH-producing pituitary tumors are recognized and characterized. The significance of finding a normal pituitary gland with or without Crooke's changes is also discussed.
- Markers of early atherosclerosis, oxidative stress and inflammation in patients with acromegaly. [JOURNAL ARTICLE]
- Pituitary 2014 Dec 13.
Data regarding atherosclerosis in acromegaly is controversial in literature. We aimed to investigate the markers of early atherosclerosis, oxidative stress, inflammation and their relationships with each other in acromegaly.Thirty-nine patients with acromegaly and 40 control subjects were enrolled. Patients were classified into two groups; active acromegaly (AA) and controlled acromegaly (CA). Controls were matched by age, gender, body mass index and presence of cardiovascular risk factors. Flow mediated dilatation (FMD), carotid intima media thickness (CIMT), epicardial adipose tissue thickness (EAT) were measured and serum levels of oxidative stress parameters, high mobility group box 1 protein (HMGB1) and high sensitive CRP (hs CRP) were evaluated.Significantly decreased FMD, increased CIMT and EAT were found in patients with acromegaly compared to controls (p < 0.01, p < 0.05, p < 0.001, respectively). EAT correlated negatively with FMD (r = -0.24, p = 0.038) and positively with CIMT (r = 0.37, p < 0.01). Presence of acromegaly, hypertension and age were found to be the predictors of early atherosclerosis (p < 0.05). Hs CRP was decreased in AA compared to controls (p = 0.01). There were no significant differences for HMGB1 and oxidized LDL (ox-LDL) cholesterol levels and total antioxidant capacity (TAC) between AA, CA and controls (p > 0.05).Early atherosclerosis measured with FMD, CIMT and EAT may exist in acromegaly. However, decreased hs CRP and unchanged HMGB1, ox-LDL and TAC levels suggest that inflammation and oxidative stress do not seem to contribute to the development of atherosclerosis in these patients.
- Current drug withdrawal strategy in prolactinoma patients treated with cabergoline: a systematic review and meta-analysis. [JOURNAL ARTICLE]
- Pituitary 2014 Dec 12.
Cabergoline is a recommended first-line dopamine agonist for prolactinoma treatment, which is withdrawable for some cases. However, the optimal withdrawal strategy and the accurate recurrence rate associated with cabergoline withdrawal remains uncertain.To assess the current recurrence rate of hyperprolactinemia and possible favorable factors associated with cabergoline withdrawal in prolactinoma patients.The databases of PubMed, EMBASE, and Web of Science were searched up to May 2014 to identify studies containing data of recurrent hyperprolactinemia in prolactinoma patients after cabergoline withdrawal. Meta-analysis, including sensitivity analysis, meta-regression analysis, and subgroup analysis were performed.When the patients who received cabergoline withdrawal were pooled, it was found that the hyperprolactinemia recurrence rate was 65 % by a random effects meta-analysis [95 % confidence interval 55-74 %]. In a random effects meta-regression adjusting for optimal withdrawal strategies, CAB dose reduced to the lowest level before withdrawal was associated with treatment success (p = 0.006), whereas CAB treatment longer than 2 years showed no trend of effect (p = 0.587). Patients who received the lowest CAB dose and presented a significant reduction in tumor size before withdrawal were more likely to achieve the best success (p < 0.001).Our meta-analysis shows that hyperprolactinemia recurs after cabergoline withdrawal in a majority of patients. The probability of success favors patients who have achieved normoprolactinemia and considerable reduction in tumor size by low dose of cabergoline treatment. In addition, our study further suggests that a beneficial strategy is associated with tapering CAB dose before withdrawal but not with CAB treatment duration longer than 2 years.
- Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach. [JOURNAL ARTICLE]
- Pituitary 2014 Dec 10.
Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope.22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss).22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue.Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.
- New oral anticoagulants and pituitary apoplexy. [JOURNAL ARTICLE]
- Pituitary 2014 Nov 23.
- Update on radiation therapy in patients with Cushing's disease. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 31.
Radiation therapy is an important therapy for patients with Cushing's disease who are not in remission or relapse after transsphenoidal pituitary surgery and are not considered surgical candidates. The development of stereotactic radiation therapy, using gamma knife, linear accelerators or proton beam based methods, has enabled selective radiation delivery to the target while minimizing exposure of healthy tissues. In patients whose tumors are sufficiently distant from the optic apparatus, stereotactic radiation therapy can be delivered in a single session, a procedure termed radiosurgery, which significantly improves patient convenience.Original articles on radiation therapy in Cushing's disease, published during the past 12 months (2013-2014), were identified and pertinent data extracted.Recent studies have reported on the outcomes of patients with Cushing's disease who received mostly stereotactic radiation therapy. While tumor control has been excellent, biochemical remission was less consistently achieved. Some studies suggested that stereotactic radiation may lead to biochemical remission faster than conventional radiation therapy. In addition, retrospective data have suggested that withdrawing medical therapy around the time stereotactic radiation therapy is administered might lead to a faster biochemical response. Regardless of the radiation therapy method, biochemical recurrences may develop and these patients are at long-term risk of developing anterior hypopituitarism and require lifelong periodic endocrine follow-up. Other, less frequent complications may include cranial neuropathies, secondary tumor formation or temporal lobe necrosis. It is plausible that complications may be less frequent after stereotactic radiation therapy, but this requires confirmation.Radiation therapy is an effective second line therapy in patients with Cushing's disease. Ongoing refinements in delivery of radiation therapy are anticipated to lead to improved patient outcomes, but long-term follow-up data, including adequate control groups, are needed to fully investigate this possibility.
- Comparison of multifocal visual evoked potential, static automated perimetry, and optical coherence tomography findings for assessing visual pathways in patients with pituitary adenomas. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 28.
There have been no studies investigating the correlation between structural [thickness of the retinal nerve fiber layer (RNFL) as determined by optical coherence tomography (OCT)] and functional [Humphrey visual field (HVF) or visual evoked potential (VEP) amplitude] measures of optic nerve integrity in patients with pituitary adenomas (PA).Patients with PAs were recruited between September 2010 and September 2013. OCT, standard automated perimetry (SAP), and multifical VEP (mfVEP) were performed. Agreement between OCT, SAP, and mfVEP values in classifying eyes/quadrants was determined using AC1 statistics. Pearson's correlation was used to examine relationships between structural and functional data.In total, 88.7 % of the eyes tested showed abnormal SAP findings and 93.7 % showed abnormal mfVEP findings. Only 14.8 % of the eyes showed abnormal OCT findings. The agreement between SAP and mfVEP findings was 88.9 % (AC1 = 0.87). The agreement between OCT and mfVEP findings was 24.2 % (AC1 = -0.52), and that between OCT and SAP findings was 21.5 % (AC1 = -0.56). The correlation values between RNFL thickness and the functional measurements were -0.601 for the mfVEP score (P = 0.000) and -0.441 for the SAP score (P = 0.000). The correlation between the mfVEP and SAP scores was -0.617 (P = 0.000).mfVEP, SAP, and OCT provided complementary information for detecting visual pathway abnormalities in patients with PAs. Good agreement was demonstrated between SAP and mfVEP and quantitative analysis of structure-function measurements revealed a moderate correlation.
- Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy? [JOURNAL ARTICLE]
- Pituitary 2014 Oct 19.
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.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).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.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.
- Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 15.
Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up.To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time.We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time.From 83 patients initially with IGHD, 37 (45 %) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38 %) deficiencies developed followed by TSH (31 %), ACTH (12 %) and ADH deficiency (5 %). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002).Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.