Data of phosphoproteomic analysis of non-functioning pituitary adenoma.

Here we describe data of a comprehensive phosphoproteomic evaluation of 20 non-functioning pituitary adenomas (NFPAs). Peptides from 20 tumor samples were enriched with TiO2 beads and fractioned using bRPLC and subjected to high throughput LC-MS/MS-Orbitrap Fusion™ Tribrid™ Mass Spectrometer for analysis. Upto 5 precursor ions were selected for MS/MS analysis. Data was analyzed using MASCOT and SEQUEST. Bioinformatics tools Phosphosite Plus, Gene Ontology, DAVID, and KEGG were used to determine the biological significance of identified phosphoproteins. In this study, 2508 phosphopeptides corresponding to 1345 phosphoprotein were identified. The phospho EGFR, MEK, and STAT1/3, ß-Catenin, BRAF, and HSPB1 were significantly hyperphosphorylated in the recurrent group as compared to the non-recurrent NFPA. Identification of these phosphoproteins provides a roadmap for patient stratification, prognostication for recurrence and trials for targeted therapy.

Cavernous sinus syndrome: A prospective study of 73 cases at a tertiary care centre in Northern India.

OBJECTIVES: To study the clinical and etiological profile of patients with cavernous sinus syndrome (CSS) and identify factors which could determine the etiology and influence the outcome of these patients. PATIENTS AND METHODS: This prospective observational study included 73 consecutive patients satisfying the criteria of CSS (i.e. involvement of any 2 of the 3rd, 4th, 5th and 6th cranial nerves or any one of them with radiological evidence of cavernous sinus involvement). All these patients were subjected to detailed haematological, biochemical and radiological investigations and diagnosed and treated as per guidelines. The clinical and investigational data was recorded and analysed meticulously. RESULTS: A definitive etiological diagnosis of CSS could be achieved in 86% of patients. Tumours, fungal infections and Tolosa Hunt syndrome (THS) were most common causes. On univariate analysis, diabetes, severe vision loss (visual acuity of <3/60 in at least one eye), and presence of nasal discharge showed a significantly positive association with a fungal CSS. Evidence of paranasal sinusitis, bone erosion and ICA (internal carotid artery) involvement on Gadolinium enhanced MRI (magnetic resonance imaging) of brain were significantly associated with a fungal CSS (p=0.0001), whereas involvement of orbital apex had a negative association with a neoplastic etiology (p=0.014). On multiple logistic regression, orbital apex involvement on MRI was associated with diagnosis of THS (p=0.019, OR: 18.7; 95% CI: 1.6-217.4) while MRI evidence of paranasal sinusitis (p=0.014, OR: 45; 95% CI: 2.1-94.3) and bone erosion ((p=0.019, OR: 12.5; 95% CI: 1.5-103) correlated with diagnosis of fungal CSS. 65.2% of patients (fungal CSS- 70%) had a good prognosis at six months follow up. CONCLUSION: Most patients with CSS can be diagnosed accurately and managed properly with good outcomes.

Prostatic hyperplasia in acromegaly, a myth or reality: a case-control study.

CONTEXT: Disorders of the prostate gland are more prevalent in patients with acromegaly. GH-insulin-like growth factor 1 (IGF1) axis plays an additive role in prostatic growth and development. OBJECTIVE: To correlate the structural and histopathological changes of the prostate and prostatic symptoms with GH/IGF1 in patients with acromegaly. DESIGN: Case-control study, from January 2012 to November 2013. SETTING: Tertiary referral centre university hospital in Northern India. PATIENTS: Fifty-three men with acromegaly and 50 healthy men matched for age and BMI. MAIN OUTCOME MEASURES: International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, dimensions of the prostate on trans-rectal ultrasonography, parameters on uroflowmetry, and immunopositivity with anti-IGF1 antibody in prostatic tissue biopsies. RESULTS: Despite low serum testosterone levels (8.9 nmol/l vs 14.3 nmol/l, acromegaly vs control), patients with acromegaly had marginally higher IPSS, PSA levels, and grades of enlarged prostate and obstructive features on uroflowmetry compared with controls. Dimensions of the prostate on ultrasonography were also significantly higher in patients. These changes were present irrespective of age, current gonadal status, and disease activity. Evidence of prostatic hyperplasia on biopsy was seen in six of 14 patients (42.8%) who underwent prostatic biopsy while it was absent in the controls. Immunohistochemistry with anti-IGF1 antibody showed moderate positivity in all the 14 patients who underwent biopsy with benign prostatic hyperplasia, compared with mild positivity in 21% of controls. Similarly, 14 control patients with prostatic malignancies showed variable positivity, four patients had strong, two each had mild and moderate positivity, while six were negative. CONCLUSIONS: In patients with acromegaly, there is a higher frequency of structural changes in the prostate, along with greater prostatic volume and obstructive features, compared with healthy controls, irrespective of age, gonadal status, and disease activity.

Choice of fluid therapy in patients of craniopharyngioma in the perioperative period: A hospital-based preliminary study.

BACKGROUND: Electrolyte imbalance and acute diabetes insipidus (DI) are the most common complications in patients undergoing craniopharyngioma surgery. Improper management of water and electrolyte imbalance is common cause of morbidity and mortality. Data is sparse and controversial regarding the choice of fluid therapy in this population during perioperative period. METHODS: In this retrospective-prospective study involving 73 patients (58 retrospective), the type of fluid therapy was correlated with occurrence of hypernatremia, hyponatremia, DI, morbidity, and mortality. In the retrospective study, 48 patients received normal saline and 10 received mixed fluids as per the prevailing practice. In the prospective group, five patients each received normal saline, half normal saline, and 5% dextrose randomly. RESULTS: The sodium values were significantly higher in first 48 h in the group that received normal saline compared with other groups (P < 0.001). The use of normal saline was associated with higher incidence of hypernatremia, DI, and mortality (P = 0.05), while the group that received 5% dextrose was associated with hyponatremia, hypoglycemia, and seizures. There was no perioperative hypotension with use of any of the fluids. CONCLUSION: Our results indicate half normal saline was fluid of choice with diminished incidence of water and electrolyte abnormalities without increase in mortality during postoperative period.

Secretory meningioma: a diagnostic pitfall.

CONTEXT: Secretory meningioma is a rare subtype of meningiomas, displaying epithelial and secretory differentiation of meningothelial cells. It has unique radiological, morphological, and immunohistochemical features, but runs a benign course. Radiological picture because of the variable degrees of peritumoral edema can be confused with aggressive neoplasms. Morphologically, it is difficult to distinguish secretory meningioma from other tumors having a clear cell appearance and aggressive clinical behavior. MATERIALS AND METHODS: Retrospective analysis over a period of 16 years (1997-2012) brought out five cases diagnosed as secretory meningioma. The slides were restained and subject to special stains and immunohistochemistry and the clinical details were retrieved. RESULTS: On histopathology, the tumors showed a characteristic vacuolated appearance due to the presence of variably sized intracytoplasmic lumina. Another unique feature was the presence of hyaline inclusions within these intracytoplasmic lumina and in the intercellular spaces. These inclusions were periodic acid-Schiff positive diastase-resistant, yellowish-orange on Elastic Van Giesson stain and strongly carcinoembryonic antigen positive. CONCLUSION: Owing to its rarity and unique morphology secretory meningioma poses a diagnostic challenge to the pathologists. As this tumor follows a benign course, it is crucial to correctly diagnose this entity to avoid unnecessary over treatment.

Ruptured venous aneurysm of cervicomedullary junction.

BACKGROUND: Ruptured venous aneurysm is often seen with arterio-venous malformation (AVM) or developmental venous anomaly (DVA). However, isolated venous aneurysm is unusual. CASE DESCRIPTION: We present a case of ruptured venous aneurysm that presented with subarachnoid hemorrhage (SAH) and intraventricular hemorrhage (IVH). Digital substraction angiography (DSA) revealed a saccular contrast filling pouch in the left lateral aspect of cervicomedullary junction (CMJ). Endovascular intervention was not a viable option. During surgery, a saccular pliable structure approx. 1.5 × 1 cm was found in the subarachnoid space that was clipped and excised. There were no arterial feeders, no evidence of surrounding AVM, and no dilated perimedullary vein. CONCLUSION: This is perhaps the first reported case of ruptured venous aneurysm (without associated AVM) of CMJ, which was successfully managed surgically. The possible etiologies remain an unnoticed head trauma or a congenital vessel wall abnormality. Surgically clipping and excision remains the treatment of choice for such lesion.

Diagnostic utility of serum GH, IGF-1 and IGFBP3 in patients of acromegaly with uncontrolled diabetes: a pilot study.

PURPOSE: Diagnosis of acromegaly in presence of uncontrolled diabetes mellitus is not well validated. METHOD: The study included 10 patients of active acromegaly with uncontrolled blood glucose, 10 patients of type 2 diabetes mellitus with poor glycemic control and 10 healthy subjects. The growth hormone level following oral glucose tolerance test and insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) were done at baseline in all the 3 groups and it was repeated after short term glycemic control in type 2 diabetics and acromegalics with diabetics RESULTS: In the acromegalic group the basal GH value was very high (36.5 + 1.6) ng/ml and it was non-suppressible (32.5 + 1.43) ng/ml after OGTT. The mean IGF-1 and IGFBP-3 values were also high at baseline (208.38 + 38.51) ng/ml, and 7322 + 370 ng/ml respectively. In the non-acromegalic diabetic patients, the basal growth hormone value was marginally elevated (2.3 + 0.02) ng/ml. However, it was suppressible to 0.2 + 0.04 ng/ml after oral glucose load. In them the IGF-1 and IGFBP-3 values were not elevated and comparable to that of healthy controls. CONCLUSIONS: Basal serum GH and IGFBP-3 levels are not influenced by degree of glycemic control however serum IGF-1 levels should be interpreted with caution in patients of acromegaly with diabetes. Oral glucose load test has discriminating ability to diagnose acromegaly even with poorly controlled diabetes.

Congestive heart failure in acromegaly: A review of 6 cases.

BACKGROUND: Though cardiac involvement is common in acromegaly, overt congestive heart failure is uncommon. MATERIALS AND METHODS: This is retrospective analysis of hospital record between 1996 and 2007. We analyzed records of 150 consecutive patients with acromegaly. We included the patients with acromegaly those who had overt congestive heart failure either at presentation or during the course of illness for the present analysis. The diagnosis of acromegaly and congestive cardiac failure were based on standard criteria. RESULTS: Out of 150 patients with acromegaly, 6 patients had overt CHF (4.0%), of which 4 presented with the features of CHF and 2 developed during the course of illness. Three patients had hypertension and 1 had diabetes. Baseline echocardiography showed severe biventricular dysfunction and global hypokinesia in all. Angiography showed dilated hypokinetic left ventricle with normal coronaries in 3, it was confirmed at autopsy in 1. Three underwent trans-sphenoidal surgery, 1 received somatostatin analogue as primary treatment modality. Normalization of growth hormone and IGF-1 led to improvement in cardiac function in 1, 1 patient lost to follow up, and 4 died during the course of illness. In 1 patient, autopsy was performed and cardiac specimen revealed normal coronaries, concentric ventricular hypertrophy, and dilatation with myofibrolysis and interfascicular fibrosis. CONCLUSION: Prevalence of overt CHF is 4% in present series. Overt CHF carries poor prognosis and hence, this complication should be recognized at earliest, and medical management to normalized cardiac function should be given utmost priority.

Pituitary metastasis as a presenting manifestation of silent systemic malignancy: A retrospective analysis of four cases.

BACKGROUND: Pituitary metastasis as a presenting manifestation of silent systemic malignancy is rare. We describe four such cases. MATERIALS AND METHODS: Four patients (0.7%) of malignancy with pituitary metastasis out of 540 patients of sellar mass within a period of 10 years were analyzed for clinical, hormonal and radiological findings. RESULT: The age range of these patients was 39-60 years with lag time ranging from 2to 5 months. Pituitary pathology was presenting manifestation in all 4 patients including diabetes insipidus, ophthalmoplegia and variable anterior pituitary hormone deficiency. 2 patients had bronchogenic carcinoma and one each had squamous cell and adenocarcinoma with unknown primary. Diagnosis of pituitary metastasis was confirmed in three on pituitary mass histopathology and in one it was based on rapidly appearing mass in a short time. CONCLUSION: Rapidly appearing mass in the sellar region, short lag time,sudden onset of ophthalmoplegia, -symptoms and signs disproportionate to the size of mass, presence of diabetes insipidus and destroyed but normal sized sella should invoke the suspicion of pituitary metastasis.

Adolescent acromegaly: clinical parameters and treatment outcome.

BACKGROUND: Adolescent acromegaly is a rare disorder and these patients present with tall stature/gigantism, tumor mass effects and menstrual irregularities. PATIENTS AND METHODS: 34 consecutive (26 males) patients having onset of disease prior to 21 years of age were included in this retrospective analysis. Their clinical features and treatment outcome were studied. RESULTS: Mean age and lag time at presentation were 21.6 +/- 3.9 years and 5.1 +/- 3.5 years respectively. Common presenting manifestations included acral enlargement, tumor mass effects and menstrual irregularities. Mean height at presentation was 174.6 +/- 13.7 cms (range: 150-210 cm) and one third had gigantism (height > or =97th percentile, WHO growth charts). Hypertension and glucose intolerance were seen in 15% and 23.5% respectively. Mean nadir GH after glucose load was 58.2 +/- 13.7 ng/ml and IGF -1 was 534.8 +/- 132.8 ng/ml. Half of the patients had concomitant hyperprolactinemia. Almost all (97%) had macroadenoma and anterior pituitary hormone deficiencies were frequent (75%). Patients with gigantism were younger (19.6 +/- 4.9 vs. 22.6 +/- 2.9 years; p = 0.001), had higher GH values (66.68 +/- 27.22 vs. 53.98 +/- 15.99 ng/ml; p = 0.04) and hypogonadism was more common (90.9% vs. 56.5%, p = 0.03) than those with normal stature. 32 patients (94.1%) were treated primarily with surgery, 7 (21.9%) received post operative radiotherapy. Mean duration of follow up was 33.1 +/- 10.1 months. Only 30% had nadir GH values of <1 ng/ml. CONCLUSION: One third of adolescent patients had acrogigantism. These patients were younger, had higher GH levels and concurrent hypogonadism was more common. Cure could be achieved only in about one third of the patients.

Effect of pneumoperitoneum on intracranial pressure during supratentorial craniotomy: a case report.

Laparoscopic surgery has become the method of choice for many procedures previously performed by open techniques. However, its use in patients with a potentially decreased intracranial compliance warrants caution. We report a case of combined glioma excision and laparoscopic cholecystectomy procedures with evaluation of the effects of pneumoperitoneum on ICP and operative field. The clinical implications, safety and recommendations of conducting laparoscopic surgeries in neurosurgical patients are discussed. Performing pneumoperitoneum in patients with marginal intracranial compliance needs interdisciplinary discussions and ICP monitoring is mandatory.

Tamoxifen use in Indian women--adverse effects revisited.

BACKGROUND: Tamoxifen is generally considered a safe drug for Indian women with breast cancer. Indian women seem to tolerate tamoxifen therapy better than western women, but there are no data regarding safety and local adverse effect profiles in typical Indian populations. METHODS AND RESULTS: A total of 3,000 case records of patients who had received tamoxifen daily for any period of time, between January 1988 and December 2007, were identified for study. Hot flashes were reported by 800 (26%), mild vaginal dryness by 450 (15%) and vaginal discharge by 300 (10%), with vaginal bleeding experienced by 40 (1.3%) patients. A total of 1,100 (36.6%) asymptomatic patients had a thickened endometrium(defined as >8mm in thickness) on ultrasonography. Endometrial curettage was performed in all of these. None of the patients developed endometrial carcinoma. Fatty infiltration of liver was found in 1,440 (48%) patients with a mean time interval for development of 7 months (range 6-30 months). CONCLUSIONS: Fatty infiltration of liver is found in almost half of the Eastern Indian women who receive tamoxifen. Increased endometrial thickness, which remains asymptomatic, was documented in more than one third of patients on ultrasound examination. Tamoxifen seems to have a negligible potential for causation of uterine malignancies in eastern Indian women. Rates of hysterectomies in Indian patients on tamoxifen are substantially lower than those of western patients on tamoxifen.

Lead-induced peripheral neuropathy following Ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.

Shunt surgery effects on cerebrospinal fluid flow across the aqueduct of Sylvius in patients with communicating hydrocephalus.

We aimed to visualize and quantify the flow of cerebrospinal fluid (CSF) across the aqueduct of Sylvius in patients with communicating hydrocephalus using phase contrast MRI, and to evaluate the effect of ventriculoperitoneal (VP) shunt surgery on flow. We investigated aqueductal CSF flow using cine cardiac-gated phase contrast MRI in 10 normal volunteers and 10 patients with communicating hydrocephalus (who underwent VP shunt surgery). For qualitative evaluation, we used an in-plane phase contrast sequence in the midsagittal plane. Quantitative through-plane measurements were performed in the axial plane perpendicular to the aqueduct. The aqueduct area ranged from 0.02 cm(2) to 0.27 cm(2) in the shunt group; and from 0.01 cm(2) to 0.04 cm(2) in the control group (p<0.05). Aqueductal stroke volume (mean, standard deviation SD) ranged from 1.9 microL to 33.17 microL (17.41 microL, 10.1132) in the control group; and from 5.63 microL to 256 microL (87.20 microL, 79.0383) in the study group. Post-operatively the aqueductal stroke volume reduced significantly, ranging from 0.60 microL to 48.77 microL (13.19 microL, 18.08) (p<0.05). Peak systolic velocity (PSV) values in the patients before shunt surgery ranged from -1.05 cm/s to -8.10 cm/s (-4.39cm/s, 2.7619) and peak diastolic velocities (PDV) ranged from 0.62 cm/s to 5.16 cm/s (3.33 cm/s, 1.4451). Post- shunt; PSV values ranged from -0.37 cm/s to -3.90 cm/s (1.78 cm/s, 1.5143) and PDV range was 0.32 cm/s to 4.43 cm/s (1.78 cm/s, 1.6782). The post-operative reduction in velocity was significant (p<0.05). Thus, the aqueductal CSF flow after VP shunt was similar to flow in healthy volunteers.

Rational use of glucocorticoid during pituitary surgery--a pilot study.

BACKGROUND & OBJECTIVE: The conventionally used perioperative glucocorticoid replacement protocol in patients with pituitary tumours is far from optimal. In this study we evaluated the validity of a modified protocol for perioperative glucocorticoid replacement in non-functioning pituitary macroadenomas. METHODS: A total of 24 consecutive patients with non functioning pituitary macroadenomas were included in this interventional study. Patients with a pre-operative 0800 h cortisol of > or = 350 nmol/l (> or = 12.6 microg/dl) did not receive glucocorticoid replacement during perioperative (d(0)-d-(2)) period, while those with < or = 100 nmol/l (< or = 3.6 microg/dl) received glucocorticoid replacement. Those patients with 0800 h cortisol value between > 100-349 nmol/l (> 3.6-12.6 microg/dl) required them to undergo an insulin induced hypoglycaemia (IIH). In response to IIH, patients with a peak cortisol of < 550 nmol/l (< 19.8 microg/dl) received glucocorticoid replacement. Post-operatively, patients on day 3 with 0800 h cortisol of < or = 100 nmol/l (< or = 3.6 microg/dl) received hydrocortisone 10 mg/m(2) per day; those between > 100-449 nmol/l (> 3.6-16 microg/dl) received hydrocortisone replacement only if they had symptoms of adrenal insufficiency (AI) or during stress; while patients with > or = 450 nmol/l (> or = 16.0 microg/dl) did not receive any glucocorticoid replacement. Retesting was done at 12 wk in 23 subjects based on the algorithm. RESULTS: Pre-operatively, 8 (35%) patients were hypocortisolic and received glucocorticoid supplementation, thereby sparing 15 (65%) subjects from glucocorticoid replacement. On d(3) of surgery, 13 (57%) patients were hypocortisolic, but only 6 with serum cortisol of < or = 100 nmol/l (< or = 3.6 microg/dl), had symptoms and were substituted with glucocorticoid. Remaining seven patients, with serum cortisol between >100-349 nmol/l (> 3.6-12.6 microg/dl), were asymptomatic and advised glucocorticoid support only during stress but none required. Overall, 17 (74%) patients were spared from unnecessary glucocorticoid support. At 12 wk, 13 (57%) patients were hypocortisolic and only 6 either with serum cortisol level of < or = 100 nmol/l (< or = 3.6 microg/dl) or symptomatic for AI received glucocorticoids. Post-operative complications including diabetes insipidus and CSF leak remarkably decreased. INTERPRETATION & CONCLUSION: The protocol used was safe and spared unnecessary use of glucocorticoids peri- and post-operatively. However, more number of patients are to be studied to substantiate the validity of this protocol.

Imaging features of endolymphatic sac tumours: case report with review of literature.

Papillary endolymphatic sac tumours (ELSTs) are rare lesions of the temporal bone often confused with other more common entities. However, the radiologic differentiation is important for both surgical planning and also to alert the pathologist as regards the true origin. We present a case of a large ELST with some specific radiological findings.

Retroperitoneal plexiform neurofibroma mimicking psoas abscesses.

Retroperitoneal plexiform neurofibroma is a rare finding in neurofibromatosis type I, or von Recklinghausen's disease. A case of retroperitoneal plexiform neurofibroma mimicking psoas abscesses is reported here with its CT and MRI findings.