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- Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas. [JOURNAL ARTICLE]
- Pituitary 2014 Mar 6.
The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and sub-total resection), and operative complications.Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis.Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21-3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24-6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00-4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24).Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate.
- Angiolipoma of the sellar region. [JOURNAL ARTICLE]
- Pituitary 2014 Feb 22.
- Central hypothyroidism in adults: better understanding for better care. [JOURNAL ARTICLE]
- Pituitary 2014 Feb 20.
Central hypothyroidism (CH) is a rare cause of hypothyroidism generally related to a hypothalamic-pituitary disorder or arising as an iatrogenic complication. In adults, CH may be secondary to quantitative and/or qualitative alterations in thyroid-stimulating hormone (TSH) secretion. The disease is difficult to diagnose clinically because it lacks specific clinical signs and these may be masked by other anterior pituitary hormone secretion deficiencies. In patients with long-standing and marked CH, a diagnosis may be made based on low free T4 levels and normal, low or moderately increased TSH levels. In patients with early-stage or moderate CH, exploration of the circadian TSH cycle, determination of TSH response after a TRH test or recombinant TSH injection, estimation of TSH index, or evaluation of peripheral indexes of thyroid hormone metabolism may be required to establish a diagnosis. Regarding treatment, patients should receive levothyroxine replacement therapy, but hormone objectives during follow-up need to be precisely determined in order to reduce cardiovascular risks and to improve the quality of life of patients.
- Pons herniation into skull base after cabergoline therapy of giant prolactinoma. [JOURNAL ARTICLE]
- Pituitary 2014 Feb 13.
Pons herniation after cabergoline therapy for giant prolactinoma is a complication not documented in literature.We report a medium aged patient who developed secondary hemiparesis after 18 months of medical treatment. MRI revealed pons herniation into the clivus. There was improvement with conservative treatment. Secuencial MRIs are presented showing the tumor at the moment of the diagnosis, tumor shrinkage and pons herniation.Some studies have shown that a significant and rapid tumor shrinkage resulting from treatment with cabergoline can occur and it is thought that some complications are related with this tumor regression, as in the presented case.
- Discordance between growth hormone and insulin-like growth factor-1 after pituitary surgery for acromegaly: a stepwise approach and management. [JOURNAL ARTICLE]
- Pituitary 2014 Feb 5.
Follow-up management of patients with acromegaly after pituitary surgery is performed by conducting biochemical assays of growth hormone (GH) and insulin-like growth factor-1 (IGF1). Despite concordant results of these two tests in the majority of cases, there is increasing recognition of patients who show persistent or intermittent discordance between GH and IGF1 (normal GH and elevated IGF1 or vice versa).In this narrative review, the last three decades materials on the issue of discrepancy between GH and IGF1 were thoroughly assessed.Various studies have obtained different discordance rates, ranging from 5.4 to 39.5 %. At present, despite the use of current sensitive assays and more stringent criteria to define remission, the rate of discordance still remains high. A number of mechanisms have been proposed to explain the postoperative discordance of GH and IGF1 including; altered dynamics of the GH secretion after surgery, early postoperative hormone assay, inaccurate or less sensitive tests and laboratory errors, too high cut-off point for GH suppression in the GH assays, GH nadir values not adjusted to age, sex, and body mass index, the influence of concomitant medication, co-existing physiologic and pathologic conditions, and many other proposed reasons. Nevertheless, the underlying mechanisms are still far from clear, and the solution continues to evade complete elucidation. Similarly, the impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear.As a challenging clinical problem, a stepwise evaluation and management of these patients appears to be more rational.
- Salivary cortisol is a useful tool to assess the early response to pasireotide in patients with Cushing's disease. [JOURNAL ARTICLE]
- Pituitary 2014 Jan 31.
Late night salivary cortisol (LNSC) is useful for diagnosing hypercortisolism and monitoring patients with Cushing's disease (CD) following pituitary surgery. It may also be a better index of cortisol secretion than serum cortisol or urinary free cortisol (UFC). No data regarding the role of LNSC in the early monitoring of patients with CD receiving drug therapy has been published. We investigated the value of LNSC in monitoring the short-term efficacy of pasireotide.Seven patients who were enrolled in a phase II study investigating the efficacy of pasireotide in CD (CSOM230B2208) were included in this analysis. Patients self-administered subcutaneous pasireotide 600 μg bid for 15 days. LNSC and UFC levels were assessed at baseline and day 15.At baseline, all patients had elevated LNSC which was correlated significantly with UFC levels (r = 0.97, P = .0002). At day 15, LNSC was reduced in six patients. LNSC decreases were observed from day 1 (-20 %) and persisted until day 15 (overall mean reduction from baseline -51 %), with the greatest decrease on day 5 (-58 %). At day 15, UFC levels were decreased in all patients and normalized in one that restored also salivary cortisol rhythm.In patients with CD, pasireotide rapidly reduced and normalized both UFC and LNSC levels. LNSC may be a simple, non-invasive biomarker to assess the early response to pasireotide, particularly in determining whether cortisol rhythm is normalized in patients with normalized UFC levels. Further studies are warranted.
- Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior. [JOURNAL ARTICLE]
- Pituitary 2014 Jan 28.
It is becoming evident that long non-coding RNAs (lncRNAs) participate in diverse biological processes via distinct mechanisms. Many lncRNAs have altered expression and likely to have functional roles in tumorigenesis. Although loss of maternally-expressed gene 3 (MEG3) expression has been detected in non-functioning pituitary adenomas (NFPAs), there are no published reports regarding the association between MEG3 expression and the invasive ability of NFPAs. Moreover, the roles of Hox transcript antisense intergenic RNA (HOTAIR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in NFPAs have not been examined. To investigate the role of MEG3, HOTAIR, and MALAT-1 in NFPA development and invasion.MEG3, HOTAIR, MALAT-1 and proliferating cell nuclear antigen (PCNA) were detected in 52 NFPA samples and seven normal human anterior pituitaries using real-time quantitative reverse transcription polymerase chain reaction.MEG3 lncRNA levels gradually decreased whereas HOTAIR lncRNA levels gradually increased from normal anterior pituitaries to non-invasive NFPAs to invasive NFPAs. There was a significant association between MEG3 (P < 0.01) and HOTAIR (P < 0.05) expression and the biological behavior of the tumor. Furthermore, PCNA mRNA levels markedly increased in invasive NFPAs compared to non-invasive ones (P < 0.01). In addition, PCNA mRNA negatively correlated with MEG3 lncRNA levels (P < 0.05).MEG3 and HOTAIR expression may correlate with NFPA development and invasion.
- Metastatic involvement of the pituitary gland: a systematic review with pooled individual patient data analysis. [JOURNAL ARTICLE]
- Pituitary 2014 Jan 21.
To report a rare case of pituitary metastasis (PM) from hepatocellular carcinoma (HCC) and help better understand the incidence of PM and its most common presenting symptoms through a pooled individual patient data analysis.Literature regarding PM was systematically reviewed with a pooled individual patient data analysis conducted. Pooled individual data analysis result is also compared with the result in a most recent systematic review.Our results demonstrate that the incidence of PM among all intracranial metastases is 0.87 % (95 % CI 0.56, 1.18); it is 1.9 % (95 % CI 1.46, 2.34) among all autopsied cancer cases; it is 11.56 % (95 % CI 7.08, 16.04) among all breast cancer patients who had hypophysectomies and 12.83 % (95 % CI 10.5, 15.16) among all autopsied breast cancer patients. The fixed effect model showed that the incidence of PM in breast cancer patients group is significantly higher (p < 0.001) with an odds ratio of 6.71 (95 % CI 4.24, 10.61). Breast and lung cancer are the most common primary cancer of PM with a percentage of 37.2 and 24.2 respectively. The next most common primary sites are prostate and kidney respectively, although the percentages for each are only about 5. Diabetes insipidus (DI) remains the most common symptom among all reported PM cases with a pooled incidence of 42.34 % (95 % CI 36.15, 48.53). Although not significant (χ(2) = 2.846, df = 1, p = 0.061), it is less common in the most recent reported cases which has a pooled incidence of 32.76 % (95 % CI 20.31, 45.21). DI is extremely rare in the reported PM cases from HCC (none of the eight cases presented with DI). The symptoms of anterior hypopituitarism (23.68 vs 39.66 %, p = 0.015), visual deterioration (27.89 vs 41.38 %, p = 0.039), cranial nerve palsies (21.58 vs 41.38 %, p = 0.003) and headaches (15.79 vs 32.76 %, p = 0.005) were reported significantly higher than previously described in the literature.Pituitary metastasis is rare in patients with cancer, and the pituitary gland is an uncommonly involved location in patients with intracranial metastases. With advanced diagnostic imaging techniques and increased awareness about the manifestation of sellar lesions, the incidence of cranial nerve palsies and anterior pituitarism are higher than reported. This information may allow earlier diagnosis of PM.
- Pituitary adenoma with gangliocytic component: report of 5 cases with focus on immunoprofile of gangliocytic component. [JOURNAL ARTICLE]
- Pituitary 2014 Jan 16.
Pituitary adenomas with gangliocytic component are rare tumors of the sellar region that are composed of pituitary adenoma cells and a ganglion cell component. Their histogenesis and hence nosology is not yet resolved because of the small number of cases reported and lack of large series in the literature.Herein we report five cases of pituitary adenoma with gangliocytic component to add knowledge to this rare neoplasm.Three cases are functional mammosomatotroph adenomas, one case is functional sparsely granulated somatotroph adenoma and the other is functional corticotroph adenoma. Gangliocytic component showed immunohistochemical expression of hormones in three cases. The ganglion cells were prolactin immunoreactive in case 1, GH and TSH immunoreactive in case 5 and showed expression of prolactin, TSH, ACTH and FSH in case 4. Three cases had undergone more than one surgery of which two had gangliocytic cells only in the recurrent tumors whereas the third case showed gangliocytic cells only in the initial tumor.The cases are discussed with clinical and histological features and a brief review of the literature considering the histogenesis is included.
- Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary. [JOURNAL ARTICLE]
- Pituitary 2014 Jan 9.
Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary.The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially.GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (p < 0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (p < 0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (p < 0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke's remnant, the putative pituitary stem cell niche, and in corticotropes.Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis.