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 Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment  |
| 01/06/2017 00:00 |
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Abstract
Background
About 80% of prolactinomas respond to dopamine agonists (DA) with hormonal normalization and tumor shrinkage. Mechanisms of DA resistance include reduction of dopamine receptor subtype 2 (DRD2) expression, short and long isoform ratio and post-receptor mechanisms. It was suggested that polymorphisms in the gene encoding dopamine receptor subtype 2 gene (DRD2) could be associated with variable effectiveness of cabergoline (CAB).
Objective
To assess the influence of DRD2 polymorphisms in responsiveness of CAB treatment in patients with prolactinoma.
Study design and patients
Cross-sectional retrospective case?control study analyzing the frequency of five DRD2 polymorphisms in 148 patients with prolactinoma and 349 healthy subjects. The association of genetic variants and clinical characteristics with CAB responsiveness was performed in 118 patients (mean age at diagnosis 29 years; range 11?61 years) with hormonal evaluation. Patients with prolactin (PRL) normalization were considered as responders.
Results
No association in genotypes and allele proportions was found comparing patients and controls. On pharmacogenetic study, 118 patients on CAB were included and 20% were non-responders. No association was found between clinical characteristics (gender, age, PRL level and tumor size at diagnosis) and polymorphisms of DRD2 with CAB responsiveness. Otherwise, there was association between polymorphisms rs1076560 (allele A) and rs1800497 (allele T) and the presence of macroadenomas.
Conclusion
No correlation was found between DRD2 polymorphisms and CAB responsiveness in patients with prolactinoma. More data are necessary in order to assess the influence of DRD2 genotyping on DA treatment response.
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| Inhibition of neuronal nitric oxide synthase activity does not alter vasopressin secretion in septic rats |
| 01/06/2017 00:00 |
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Abstract
Background/Purpose
During the early phase of sepsis, hypotension is accompanied by increase of plasma vasopressin hormone (AVP) levels, which decline during the late phase. This hypotension is due in part to increase of nitric oxide (NO) synthesis by nitric oxide synthase (NOS) enzyme. Neuronal isoform of this enzyme (nNOS) is present in vasopressinergics neurons of hypothalamus, but its role in vasopressin secretion during sepsis is unknown.
Methods
We evaluated the role of nNOS in NO production and vasopressin secretion during sepsis. Wistar rats received 7-nitroindazole (50 mg/kg, i.p.), an inhibitor of nNOS activity, or vehicle and were submitted to septic stimulus by cecal ligation and puncture (CLP). At the time points 0, 4, 6, 18 and 24 h after sepsis induction the animals were decapitated and neurohypophysis and hypothalamus were removed for analysis of vasopressin content and NOS activity, respectively. Hematocrit, serum sodium, osmolality, proteins and plasmatic AVP were quantified.
Results
Mortality was not affected by 7-nitroindazole (7-NI). Sodium and plasma proteins levels decreased after CLP and the treatment anticipated the protein loss, and delayed serum sodium decrease. Septic animals treated with 7-NI showed decrease of osmolality 4 h after CLP. Nitric oxide synthase activity in hypothalamus increased at 4 and 24 h after CLP and was reduced with 7-NI. Neurohypophysis content of AVP diminished after CLP and 7-NI did not alter this parameter. Plasma AVP levels increased at 6 h and decreased 18 and 24 h after CLP. Treatment with 7-NI did not alter plasma vasopressin levels.
Conclusion
We concluded that nNOS does not have a substantial role in vasopressin secretion during experimental sepsis.
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| SOCS2 polymorphisms are not associated with clinical and biochemical phenotypes in acromegalic patients |
| 01/06/2017 00:00 |
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Abstract
Purpose
Suppressor of cytokine signaling 2 (SOCS2) is a STAT5b-regulated gene and one of its functions is to influence growth and development through negative regulatory effects on GH/IGF-1 pathway. So, we evaluate the potential influence of SOCS2 single nucleotide polymorphisms (SNPs) on clinical and laboratorial characteristics of a large cohort of Brazilian patients with acromegaly.
Methods
Four SOCS2 SNPs (rs3782415, rs3816997, rs3825199 and rs11107116) were selected and genotyped by real-time PCR using specific Taqman probe assays. A total of 186 patients (116 women, age range 26?88 years) were evaluated.
Results
No association of SOCS2 genotypes was observed with none of the following clinical and laboratorial characteristics: age, sex, body mass index, comorbidities, basal GH, oral glucose tolerance test GH nadir, IGF-I, ULNR-IGF-I.
Conclusion
Despite of the key role of SOCS2 in the regulation of GH receptor signaling, we did not find any significant association between SOCS2 polymorphisms and acromegaly.
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| White matter involvement on DTI-MRI in Cushing?s syndrome relates to mood disturbances and processing speed: a case-control study |
| 01/06/2017 00:00 |
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Abstract
Purpose
Cushing?s syndrome (CS) is an endocrine disorder due to prolonged exposure to cortisol. Recently, microstructural white matter (WM) alterations detected by diffusion tensor imaging (DTI) have been reported in CS patients, and related to depression, but other functional significances. remain otherwise unclear. We aimed at investigating in more depth mood symptoms in CS patients, and how these relate to cognition (information processing speed), and to WM alterations on DTI.
Methods
The sample comprised 35 CS patients and 35 healthy controls. Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, State-Trait Anxiety Inventory (STAI) to assess anxiety, and processing speed was measured by the Symbol Digit Modalities Test (SDMT). DTI studies were acquired using a 3-Tesla Philips-Achieva MR-facility. Voxelwise statistical analysis of fractional anisotropy (FA), mean, axial and radial diffusivities (MD, AD, RD) data were performed using FMRIB Software Library. Correlation analysis were obtained between mood and processing speed variables, and FA, MD, AD and RD values, taking both CS patients and healthy controls.
Results
Active, controlled and cured CS patients showed greater depression (F?=?12.4, p?<?0.001), anxious state (F?=?4.8, p?=?0.005) and anxious trait (F?=?9.6, p?<?0.001) scores, than controls. Using the entire sample, depression scores correlated negatively to FA and positively to RD values. Although there were no differences in processing speed between groups, SDMT scores correlated positively to both FA and AD values.
Conclusions
There were greater depressive and anxious symptoms in CS patients than in healthy controls, but no difference in processing speed. However, DTI is related to depression and information processing speed in CS.
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| Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells |
| 01/06/2017 00:00 |
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Abstract
Purpose
Endocrine disruptors are known to modulate a variety of endocrine functions and increase the risk for neoplasia. Epidemiological data reported increased prevalence of pituitary tumors in high industrial areas while genotyping studies showed that mutations in the aryl hydrocarbon receptor (AhR) interacting protein (AIP)?chaperone to the dioxin ligand AhR?gene are linked to predisposition to pituitary tumor development. Aim of the present study was to establish whether endocrine pollutants can induce cell proliferation in normal rat pituitary cells.
Methods
Pituitary primary cultures were incubated with 250, 650 and 1250 pM benzene or 2-ethyl-phthalate for up to 96 h and viability, energy content and cell proliferation assessed. Expression of pituitary tumor transforming gene (PTTG), cyclin D1 (Ccnd1), AhR and AIP was quantified by RT-qPCR.
Results
Incubation with benzene or 2-ethyl-phthalate increased viability and energy content in pituitary cells. The endocrine disruptors also increased cell proliferation as well as Ccnd1 and PTTG expression. Increased AhR and AIP expression was observed after incubation with the two pollutants.
Conclusions
Our findings indicate that benzene and 2-ethyl-phthalate activate AhR/AIP expression and stimulate proliferation in normal rat pituitary cells. This study is the first demonstration that pollutants can induce normal pituitary cells to proliferate and provides a link between epidemiological and genomic findings in pituitary tumors.
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| Two-dimensional speckle tracking echocardiography demonstrates no effect of active acromegaly on left ventricular strain |
| 01/06/2017 00:00 |
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Abstract
Background
Speckle tracking echocardiography (STE) allows for the study of myocardial strain (?), a marker of early and subclinical ventricular systolic dysfunction. Cardiac disease may be present in patients with acromegaly; however, STE has never been used to evaluate these patients.
Objective
To evaluate left ventricular (LV) global longitudinal strain in patients with active acromegaly with normal LV systolic function.
Design
Cross-sectional clinical study.
Methods
Patients with active acromegaly with no detectable heart disease and a control group were matched for age, gender, arterial hypertension and diabetes mellitus underwent STE. Global LV longitudinal ? (GLS), left ventricular mass index (LVMi), left ventricular ejection fraction (LVEF) and relative wall thickness (RWT) were obtained via two-dimensional (2D) echocardiography using STE.
Results
Thirty-seven patients with active acromegaly (mean age 45.6?±?13.8; 48.6% were males) and 48 controls were included. The mean GLS was not significantly different between the acromegaly group and the control group (in %, ?20.1?±?3.1 vs. ?19.4?±?2.2, p?=?0.256). Mean LVMi was increased in the acromegaly group (in g/m2, 101.6?±?27.1 vs. 73.2?±?18.6, p?<?0.01). There was a negative correlation between LVMi and GLS (r?=??0.39, p?=?0.01).
Conclusions
Acromegaly patients, despite presenting with a higher LVMi when analyzed by 2D echocardiography, did not present with impairment in the strain when compared to a control group; this finding indicates a low chance of evolution to systolic dysfunction and agrees with recent studies that show a lower frequency of cardiac disease in these patients.
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| Cholesterol granulomas presenting as sellar masses: a similar, but clinically distinct entity from craniopharyngioma and Rathke?s cleft cyst |
| 01/06/2017 00:00 |
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Abstract
Purpose
Cholesterol granulomas in the sella are rare and can mimic the appearance of craniopharyngioma or Rathke?s cleft cysts. Information regarding the clinical presentation, imaging characteristics, and clinical course of sellar cholesterol granulomas can help clinicians to differentiate these lesions from other sellar cystic lesions.
Methods
We present three cases of sellar cholesterol granulomas. A literature review was performed for all cases of sellar cholesterol granulomas with individual patient data reported.
Results
We identified 24 previously reported cases in addition to our three cases. Mean age was 36.6 years (range 5?68). There were 16 (59%) females. The most common (74%) presenting symptom was endocrinological deficits, typically either isolated diabetes insipidus (DI) or panhypopituitarism. Location was intrasellar in 3 (11%), suprasellar in 6 (22%), and intrasellar/suprasellar in 18 (67%) patients. Lesions were most commonly (83%) T1 hyperintense. Gross total resection was achieved in 16 (64%) and subtotal resection in 9 (36%) patients. Of the seventeen (63%) patients presenting with varying degrees of bitemporal hemianopsia, all had improvement in vision postoperatively. It is worth noting that no cases of preoperative hypopituitarism or DI improved postoperatively. Even though gross total resection was only achieved in 64%, there was only one recurrence reported.
Conclusion
Sellar cholesterol granulomas are characterized by T1 hyperintensity, younger age, and more frequent and severe endocrinological deficits on presentation. Our review demonstrates high rates of improvement of visual deficits, but poor rates of endocrine function recovery. Recurrence is uncommon even in cases of subtotal resection.
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| Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas |
| 01/06/2017 00:00 |
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Abstract
Purpose
The pathogenesis of pituitary adenomas (PA) is complex. Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analysed and correlated with tumour and patient characteristics.
Methods
74 pituitary tumour samples (48 non-functional PA, 26 functional PAs); Immunohistochemical analysis of protein expression, retrospective analysis of MR images and in vitro analysis of octreotide treatment was carried out on GH3 cells.
Results
PTTG expression was negatively associated with age and positively with PA size, regrowth and Ki-67 index. Cyclin D1 correlated with Ki-67 and tumour size. c-MYC negatively correlated with size of tumour and age; and correlated with PTTG expression. Somatostatin analogue treatment was associated with lower Ki-67, PTTG and Cyclin D1 expression while T2 hypointense PAs were associated with lower PTTG, cyclin D1, c-MYC and Ki-67. In vitro analyses confirmed the effect of somatostatin analogue treatment on Pttg and Cyclin D1 expression.
Conclusions
Interesting and novel observations on the differences in expression of tumour markers studied are reported. Correlation between Ki-67 expression, PTTG nuclear expression and recurrence/regrowth of PAs, emphasizes the role that Ki-67 and PTTG expression have as markers of increased proliferation. c-MYC and PTTG nuclear expression levels were correlated providing evidence that PTTG induces c-MYC expression in PAs and we propose that c-MYC might principally have a role in early pituitary tumorigenesis. Evidence is shown that the anti-proliferative effect of somatostatin analogue treatment in vivo occurs through regulation of the cell cycle.
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| Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis |
| 01/06/2017 00:00 |
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Abstract
Purpose
IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear.
Methods
In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence.
Results
APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases.
Conclusions
Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.
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| Sellar and clival plasmacytomas: case series of 5 patients with systematic review of 65 published cases |
| 01/06/2017 00:00 |
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Abstract
Purpose
Parasellar plasmacytomas are rare tumors localized to the sellar region arising from plasma cells. Knowledge of clinical, imaging, surgical, and pathological characteristics is limited to single case reports.
Methods
A retrospective analysis of five primary cases was conducted, followed by systematic review of English language articles using PubMed in accordance with PRISMA guidelines.
Results
Five primary case patients include four men and one woman, ages 60?77, followed up to 3 years. A systematic review identified 65 additional patients, of whom 65% presented with cranial nerve palsies and 15% with hypopituitarism. Sixteen percent had history of known multiple myeloma (MM) while 37% were diagnosed concurrently with MM on presentation of parasellar plasmacytoma. Imaging showed median tumor size of 38 mm (range, 4?70 mm), with MRI intensity similar to that of other sellar masses. Surgical biopsy with immunohistochemical studies confirmed plasmacytoma diagnosis. Eighty-one percent underwent parasellar radiotherapy, and chemotherapy initiated in 59% of the 69 patients with MM. Overall survival rate was 74% at follow-up (median 12 months), with 18% having parasellar recurrences and 38% progressing to systemic MM after presentation of a solitary plasmacytoma (median 3 months).
Conclusions
Parasellar plasmacytomas are rare tumors that should be considered in the differential diagnosis for lesions involving the sella and arising from the clivus, especially when cranial nerve paresis is apparent, even in the absence of known MM. Although recurrence rates for parasellar plasmacytoma is low, patients should be monitored for progression to MM. Treatment depends on the presence of systemic disease at diagnosis.
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| Adipsic diabetes insipidus in adult patients |
| 01/06/2017 00:00 |
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Abstract
Introduction
Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI.
Methods
A literature search was performed to review the background, etiology, management and associated complications of this rare condition.
Results
ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI.
Conclusion
The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.
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| Cross-sectional prevalence of pancreatic cystic lesions in patients with acromegaly, a single-center experience |
| 24/05/2017 00:00 |
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Abstract
Purpose
Acromegaly is a disease associated with an increased risk for several kinds of neoplasms including colon and thyroid cancer. Although the association between acromegaly and pancreatic neoplasms has not been elucidated, it has recently been reported that GNAS gene mutations were found in 58% of intraductal papillary mucinous neoplasms (IPMNs), which are representative pancreatic cystic lesions, suggesting a link between IPMNs and acromegaly. To assess the prevalence of pancreatic cystic lesions in patients with acromegaly, we performed a retrospective cross-sectional single institute study.
Methods
Thirty consecutive acromegalic patients (20 females and 10 males; mean age, 60.9?±?11.9 years) who underwent abdominal contrast-enhanced computed tomography or magnetic resonance imaging between 2007 and 2015 at Kobe University Hospital were recruited. We also analyzed the relationship between presence of pancreatic cystic lesions and somatic GNAS mutations in pituitary tumors.
Results
Seventeen of 30 (56.7%) patients studied had pancreatic cystic lesions. Nine of 17 patients (52.9%) were diagnosed with IPMNs based on imaging findings. These results suggest that the prevalence of IPMNs may be higher in acromegalic patients in acromegalic patients than historically observed in control patients (up to 13.5%). In patients with pancreatic cystic lesions, the mean patient age was higher and the duration of disease was longer than in those without pancreatic cystic lesions (67.0?±?2.3 vs. 53.0?±?2.7 years, p?<?0.001, 15.5?±?2.4 vs. 7.3?±?2.8 years, p?=?0.04). There were no differences in serum growth hormone levels or insulin-like growth factor standard deviation scores between these two groups (21.3?±?6.4 vs. 23.0?±?7.4 ng/ml, p?=?0.86, 6.6?±?0.5 vs. 8.0?±?0.6, p?=?0.70). Neither the presence of somatic GNAS mutation in a pituitary tumor nor low signal intensity of the tumor in T2 weighted magnetic resonance imaging was associated with the presence of pancreatic cystic lesions.
Conclusions
These data demonstrate that old or long-suffering patients with acromegaly have a higher prevalence of pancreatic cystic lesions. Moreover, the prevalence of pancreatic cystic lesions may be increased in acromegalic patients.
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| Pituitary dysfunction in granulomatosis with polyangiitis |
| 24/05/2017 00:00 |
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Abstract
Purpose
Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD).
Methods
A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed.
Results
The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding.
Conclusion
GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.
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| Perioperative hypothalamic pituitary adrenal function in patients with silent corticotroph adenomas |
| 20/05/2017 00:00 |
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Abstract
Background
Silent corticotroph adenomas (SCAs) are characterized by strong ACTH immunostaining without clinical manifestations of hypercortisolism. Patients with SCAs often present with mechanical symptoms related to tumor growth. This study investigates the hypothalamic pituitary adrenal axis (HPA) characteristics after adenomectomy in patients with SCAs.
Methods
Biochemical parameters of HPA function were monitored frequently after surgical resection of non-functioning macroadenomas. Levels of ACTH, cortisol, DHEA and DHEA-S were measured frequently for 48 h after adenomectomy. HPA data of patients with SCAs (n?=?38) were compared to others (Controls) with non-secreting, ACTH-negative immunostaining adenomas of similar age and gender distribution (n?=?182) who had adenomectomy.
Result
Plasma ACTH increased (P?<?0.0001) equally in patients with SCA and controls reaching a peak at 3 h (238?±?123 vs. 233?±?96 ng/L, respectively) after extubation declining thereafter to baseline values 24?36 h. Similarly, serum cortisol levels increased (P?<?0.0001) equally in both groups reaching a maximum at 7 h (36.8?±?13.9 vs. 39.3?±?13.3 ug/dL). Serum DHEA also increased (P?<?0.001) equally in both groups in parallel to the rise in serum cortisol. Serum DHEA-S levels similarly increased (P?<?0.001) from their respective baseline (105.9?±?67.5 and 106.5?±?58.7 ug/dL) reaching their peak (154.5?±?69.5 and 153.5?±?68.6 ug/dL; respectively) at 15 h after extubation. None of the patients acquired any hormone deficits.
Conclusions
Under the maximal stimulation of the peri-operative stress, HPA function in patients with SCA behaved in an identical manner to others with ACTH-negative macroadenomas. Thus, despite the strong ACTH-positive immunostaining of these tumors, SCAs are truly non- functional.
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| ?Ectopic? suprasellar type IIa PRL-secreting pituitary adenoma |
| 19/05/2017 00:00 |
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Abstract
Background
Ectopic pituitary adenomas (EPAs) are rare, and the suprasellar cistern seems to be the most common location. At this time, no detailed original classification, diagnosis, or treatment protocols for suprasellar pituitary adenomas (SPAs) have been described.
Case description
A 19-year-old man showed visual disturbances and lack of libido for 3 years, he suffered a sharp decline in vision with only light perception in the last week. Magnetic resonance imaging scans revealed a large suprasellar cystic lesion with a normal pituitary in the sella turcica. Endocrinological findings showed an extremely high prolactin level of 1250 ng/mL. Because of the sharp decline in vision, the patient underwent total removal of the suprasellar lesion using a transfrontal interhemispheric approach. The tumor pedicle originated in the lower pituitary stalk without any connection to the anterior pituitary gland in the sella turcica, while the diaphragma sellae was incomplete. Clinical and endocrinological cure criteria were fulfilled and postoperative pathology confirmed a prolactin-secreting pituitary adenoma.
Conclusion
Ectopic suprasellar pituitary adenomas (ESPAs) are extremely rare intracranial extracerebral tumors. SPAs can be classified into three types according to their origin and their relationship with surrounding tissue. Only type III is theoretically a true ectopic, based on previous reports. Thus, ESPAs are uncommon compared to other EPAs. Our case is the first reported case of a type IIa ?E?SPA and the first description of this subtype classification until now. The pars tuberalis may be different from the pars distalis, and each subtype of adenohypophyseal cells may have different migration characteristics, which leads to different proportions of each hormone-secreting subtype in SPAs and EPAs. Transsphenoidal surgery is minimally invasive, but transcranial surgery may remain a universal option for the treatment of suprasellar lesions.
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| Prolactinoma management: predictors of remission and recurrence after dopamine agonists withdrawal |
| 18/05/2017 00:00 |
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Abstract
Objective
Prolactinomas are the most common functional pituitary tumour. Dopamine agonists (DA) are its principal treatment. The criteria that should guide therapy withdrawal and the factors that influence disease remission or relapse are not yet fully established. Our purpose is to evaluate the proportion of patients who attempted DA withdrawal, and to identify the factors that influence clinicians to try it. In addition, we aim to study the factors that are involved in prolactinoma remission/relapse after therapy withdrawal.
Methods
We retrospectively evaluated 142 patients with prolactinoma diagnosis who had been treated exclusively with DA. Firstly, the patients were divided in two groups, according to whether DA withdrawal had been attempted, or not, and the factors that might predict clinicians? decision to discontinue the therapy were then analysed. Secondly, patients who attempted withdrawal were further divided into two subgroups, based on their remission or relapse status and predictors of remission were evaluated.
Results
DA withdrawal was attempted in 35.2% of our patients. Females, subjects with lower initial serum prolactin (PRL) levels, those with microadenomas and those with longer treatment duration all had a higher probability of seeing their therapy discontinued. In the withdrawal group, the remission rate was 72%. Macroprolactinomas relapse more often than microprolactinomas (p?<?0.05). The recurrence group had higher median initial serum PRL levels and a lower mean duration of therapy, however these variables did not reach statistical significance.
Conclusion
We found a low percentage of attempt of withdrawal of DA therapy in the subjects with prolactinoma. Our data confirms that DA therapy can be discontinued with a high remission rate. Tumour size was the main variable that affected the withdrawal outcome in our patients.
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| Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke?s cell morphology |
| 21/04/2017 00:00 |
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Abstract
Purpose
MCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as a relevant prognostic biomarker in a variety of cancers, including pituitary adenomas. The purpose of this study was to assess whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort of ACTH-immunopositive adenomas.
Methods
Tissue samples were obtained intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were assessed by immunohistochemical staining, while the expression of miR-106b-5p, miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR performed on RNA isolated from FFPE tissues.
Results
We have found a significant increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7 was ubiquitously overexpressed in Crooke?s cell adenomas. The expression of miR-93-5p was significantly elevated in invasive compared to noninvasive tumors. In addition, all four microRNAs from the miR-106b~25 cluster displayed marked upregulation in Crooke?s cell adenomas. Remarkably, MCM7 and miR-106b-5p both strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25 cluster expression was able to accurately differentiate invasive from noninvasive tumors and had a significant discriminatory ability to predict postoperative tumor recurrence/progression.
Conclusions
miR-106b~25 and its host gene MCM7 are potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas. Additionally, they are both significantly upregulated in rare Crooke?s cell adenomas and might therefore contribute to their aggressive phenotype.
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| Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy |
| 18/04/2017 00:00 |
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Abstract
Purpose
In pituitary apoplexy (PA), there are preliminary reports on the appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of this study was to evaluate the incidence and clinical significance of SSMT in patients with PA and a control group of surgically treated non-functioning pituitary adenomas (NFPAs).
Methods
Retrospective review of clinical and imaging variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic regression was used to identify factors associated with SSMT.
Results
There were 50 NFPA and 47 PA patients. PA patients were managed conservatively (N?=?11) or surgically (N?=?36). The median sphenoid sinus mucosal thickness was greater in the PA than NFPA groups (2.0 vs. 0.5 mm; p?<?0.001). In multivariate analysis of both the PA and NFPA groups, the presence of PA was the only factor associated with SSMT (OR 0.043, 95% CI 0.012?0.16; p?<?0.001). In multivariate analysis of the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR 0.12, 95% CI 0.026?0.54; p?=?0.006) and a more severe grade of apoplexy (OR 7.29, 95% CI 1.10?48.40; p?=?0.04), were associated with SSMT.
Conclusion
The incidence of SSMT is higher in patients with PA, especially during the acute phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory and/or infective changes.
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Pituitary 