Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Pituitary Dysfunction in Idiopathic Intracranial Hypertension: An Analysis of 80 Patients.

BACKGROUND: Empty sella is a commonly described imaging entity in patients with idiopathic intracranial hypertension (IIH). Though menstrual and hormonal disturbances have been associated with IIH, available literature lacks systematic analysis of pituitary hormonal disturbances in IIH. More so, the contribution of empty sella in causing pituitary hormonal abnormalities in patients of IIH has not been described. We carried out this study to systematically assess the pituitary hormonal abnormalities in patients with IIH and its relation to empty sella. METHODS: Eighty treatment naïve patients of IIH were recruited as per a predefined criterion. Magnetic resonance imaging (MRI) brain with detailed sella imaging and pituitary hormonal profile were done in all patients. RESULTS: Partial empty sella was seen in 55 patients (68.8%). Hormonal abnormalities were detected in 30 patients (37.5%), reduced cortisol levels in 20%, raised prolactin levels in 13.8%, low thyroid-stimulating hormone (TSH) levels in 3.8%, hypogonadism in 1.25%, and elevated levels of gonadotropins were found in 6.25% of participants. Hormonal disturbances were independent and were not associated with the presence of empty sella (p = 0.493). CONCLUSION: Hormonal abnormalities were observed in 37.5% patients with IIH. These abnormalities did not correlate with the presence or absence of empty sella. Pituitary dysfunction appears to be subclinical in IIH and responds to intracranial pressure reduction, not requiring specific hormonal therapies.

Effects of metformin on clinical, hormonal and relevant gene expression parameters in patients with acne: an observational study.

BACKGROUND: Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with polycystic ovarian syndrome (PCOS). However, the benefits of metformin in patients with acne in general are not well established. AIM: To study the effectiveness of metformin treatment in patients with acne but who do not have PCOS and to understand the mechanisms of action of metformin in acne not related to PCOS. METHOD: In this observational study, 30 patients with clinically confirmed acne vulgaris were treated with metformin (1000 mg daily) for 3 months without any other topical or systemic active intervention for their acne. The effect of metformin at the clinical, hormonal and genetic level was assessed. RESULTS: Metformin monotherapy significantly (P < 0.001) decreased the global acne grading score for acne followed by a marginal increase in insulin; with a significant (P = 0.03) increase in insulin-like growth factor-1 (IGF-1). A significant (P < 0.001) decrease in free androgen index resulting from a significant (P < 0.001) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. Homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box protein O1 (FOXO1) expression was significantly (P = 0.006) downregulated with metformin treatment at the mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely HMGCR, SQLE and ACSL5 (P = 0.001, P = 0.03, P = 0.03, respectively) were also downregulated. CONCLUSION: Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FOXO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.

Giant skull base mass need not be a tumor - a rare presentation of IgG4-related disease.

BACKGROUND: Giant intracranial 'IgG4-related' lesions are uncommon. They may present as pachymeningitis or localized mass. Here we report, probably, the largest IgG4 skull base mass ever to be reported. CASE: A 40-year male presented with headache, diplopia, right-sided sensori-neuronal hearing loss, and left spastic hemiparesis. Magnetic resonance imaging showed a lesion of 8.5 cm extending from the paranasal sinuses to the right petroclival region with uniform contrast enhancement and T2 hypointensity. Endonasal biopsy revealed respiratory epithelium with fibrosis, and lymphoplasmacytic infiltrate having IgG4 positive cells >30/HPF suggestive of 'IgG4-related' disease. Serum IgG4 was within normal levels. With oral prednisolone 60 mg given daily for 6 weeks and then tapered off over 8 weeks, he improved symptomatically. CONCLUSION: Though rare, 'IgG4-related' disease can also present as a giant skull base mass and should be kept as a differential to fungal granulomas and meningiomas. As they improve dramatically with medical management, extensive skull base resection should not be planned before obtaining a tissue biopsy, especially when there is extension into paranasal sinuses and T2 hypointensity.

Baseline renal dysfunction determines mortality following parathyroidectomy in primary hyperparathyroidism: analysis of Indian PHPT registry.

INTRODUCTION: Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited. MATERIAL AND METHODS: This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy. RESULTS: The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1-13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m2) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42-5.84)], anaemia [HR 2.45 (1.11-5.42)] and pancreatitis [HR 2.65 (1.24-5.66)] on univariate and renal dysfunction [HR 3.33 (1.13-9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values. CONCLUSIONS: Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.

Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome.

PURPOSE: Sheehan's syndrome (SS) is characterised by chronic pituitary insufficiency following a vascular insult to the pituitary in the peripartum period. There is a lack of substantial evidence on the long-term hepatic and cardiac consequences in these patients, following hormone replacement. METHODS: Patients with a diagnosis of SS were recruited for the study. Detailed clinico-biochemical and radiological evaluation were performed in all patients (n = 60). Hepatic and cardiac complications were assessed using fibroscan and echocardiography (2D speckle-tracking) respectively, in a subset of patients (n = 29) as well as age-and BMI-matched controls (n = 26). Controlled attenuation parameter (for steatosis) and liver stiffness measurement (for fibrosis) were used to define non-alcoholic fatty liver disease (NAFLD). Diastolic cardiac function was evaluated using standard criteria and systolic function by ejection fraction and global longitudinal strain (GLS). RESULTS: The mean age of the cohort was 42.7 ± 11.6 years. Multiple (≥ 2) hormone deficiencies were present in 68.8% of patients, with hypothyroidism (91.4%), hypocortisolism (88.3%), and growth hormone (GH) deficiency (85.7%) being the most common. At a mean follow-up of 9.8 ± 6.8 years, NAFLD was present in 63% of patients, with 51% having severe steatosis, which was predicted by the presence of GH deficiency and higher body mass index. Though the ejection fraction was similar, increased left ventricular GLS (18.8 vs. 7.7%) was present in a significantly higher number of patients versus controls. CONCLUSION: NAFLD, especially severe hepatic steatosis, is highly prevalent in SS. Subclinical cardiac systolic dysfunction (impaired GLS) is also more common, but of mild intensity.

The role of steroid receptors, peptides and growth factors in the aetiopathogenesis of idiopathic gynecomastia.

Idiopathic gynecomastia is a diagnosis of exclusion. We aimed to evaluate the role of steroids, peptides and growth factors in these patients. Those with bilateral idiopathic gynecomastia (n = 29) (Simon's grade IIb or III) who underwent gland excision were evaluated by immunohistochemical techniques using semi-quantitative grading for oestrogen receptor (ER), progesterone receptor (PR), aromatase, androgen receptor (AR), peptides (IGF-1, IGF-2, HER-2, parathyroid-hormone related peptide [PTHrP]) and growth factors (EGFR, TGFß). The cohort comprised 29 patients, with a mean age of 25.3 ± 5.1 years and a mean body mass index of 27.2 ± 2.3 kg/m2 . Grade IIb gynecomastia was present in 79.1% and moderate-to-severe insulin resistance (HOMA-IR >3) in 53.7% of patients. ER expression was positive in 100% samples, followed by AR (96.5%), aromatase (96.5%) and PR (93.1%). IGF-1 was expressed in 86.2% of the cohort, IGF2 in 27.5% and HER-2 in only two samples, with both showing weak immunoexpression. None of the patients had positive expression of EGFR, TGF-ß or PTHrP. There was no association between immunoexpression and gynecomastia grade. This study demonstrates the predominant role of oestrogen, aromatase and insulin resistance in the aetiopathogenesis of idiopathic gynecomastia and implicates the paracrine hyperestrogenic milieu in its causation as circulating hormones were normal.

Effects of metformin on experimentally induced acne on rabbit ear.

Evidence for the effectiveness of metformin in the treatment of acne is limited. To assess its efficacy, comedones were experimentally induced in young New Zealand rabbit ear using Isopropyl Myristate (IM) followed by metformin treatment (30 mg/kg bodyweight) for 60 days with continued IM application. In another group, to check whether metformin pre-treatment affects subsequent comedone development by IM, metformin was given for 14 days and then withdrawn (14 days) followed by comedone development with IM and metformin treatment. At different time points, dermatoscopic images of rabbit ear were taken for clinical assessment. Blood and biopsy samples were taken for hormonal assessment, histological examination and gene expression. Histologically confirmed acne model was developed in rabbit ear. Follicular size increased significantly (p = 0.0004 in both groups) upon IM application. Metformin significantly decreased comedones size as observed in dermatoscopic (p = 0.0003 in group I, p = 0.0190 in group II) and histological examination (p = 0.0313 in group I and II). However, size of comedones developed after metformin pretreatment was significantly (p < 0.0001) smaller. The lipid content of sebaceous glands decreased with metformin without any significant changes in the assessed hormones and genetic expression. Overall, metformin was found to be clinically effective in experimentally induced acne and can be used in humans.

Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome.

OBJECTIVE: To examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size. METHODS: This was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma). RESULTS: CD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m2; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005). CONCLUSION: Our cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.

Differential independent impact of the intraoperative use of navigation and angled endoscopes on the surgical outcome of endonasal endoscopy for pituitary tumors: a prospective study.

Despite widespread popularity of navigation and angled endoscopes in endonasal endoscopy, there are hardly few studies on their efficacy with the extent of resection or retreatment. This is probably the first study to assess the independent impact of these adjuncts among pituitary tumors. Patients with pituitary tumors undergoing endonasal endoscopy were prospectively studied for their demographics, clinico-radiological features, intraoperative use of navigation, and angled endoscopes, in relation to gross total resection (GTR), near total resection (NTR), endocrine remission, and retreatment. Pertinent statistical analyses were performed. Among a total of 139 patients, navigation and angled endoscopes could be used in 54 and 48 patients, respectively, depending upon their availability rather than chosen as per the case. There was no significant difference in baseline characteristics in relation to their use. The surgeon's perception of immediate benefit was noted among 51.9% while using navigation. The use of angled endoscopes towards the end of resection could help with additional tumor removal in 62.5% of patients. Overall, the use of navigation resulted in a significantly higher GTR (80.8% vs. 59.7%, OR 2.83, p = 0.01), a higher GTR/NTR (86.5% vs. 70.8%, OR 2.65, p = 0.04), and a lower retreatment rate (7.7% vs. 20.8%, OR 3.15, p = 0.05) than the others. In functioning tumors with cavernous sinus invasion, navigation had significantly increased remission rates (69.2% vs. 0%, p = 0.03). The use of angled endoscopes yielded a significantly higher GTR/NTR (91.7% vs. 70.6%, p = 0.04) and a lower retreatment rate (0% vs. 15.7%, p = 0.05) among only non-functioning adenomas. In multivariate analyses, the use of neuronavigation had a significant association with both GTR and retreatment rates (p values 0.005 and 0.02 respectively), independent of other confounding factors. The elective intraoperative use of navigation has a significant independent impact on the extent of resection and retreatment overall. While navigation results in better remission rates among functioning tumors with cavernous sinus invasion, angled endoscopy has a significant association with surgical outcomes in non-functioning tumors.

Effectiveness of dietary diabetes insipidus bundle on the severity of postoperative fluid imbalance in pituitary region tumours: A randomized controlled trial.

AIM: To test the effectiveness of nurse-led dietary diabetes insipidus (DI) bundle on the severity of postoperative fluid imbalance in pituitary region tumours. DESIGN: Blinded randomized controlled trial. METHODS: Patients aged 18-65 operated for sellar-suprasellar tumours in an Indian tertiary care centre were enrolled through total enumeration sampling and underwent randomization with allocation concealment during Sep 2018-Feb 2019. Pre-operative DI, postoperative ventilation, renal failure or decompensated diabetes mellitus were excluded. Patients in the intervention group received a nurse-led DI bundle (validated by three Delphi rounds) with four dietary components: intake of only water during thirst and avoidance of the following-added salt, high-protein foods and caffeinated drinks. Treating clinicians and the investigator assessing outcome were blinded about enrolment. Urine output, serum sodium, vasopressin requirement and hospital stay were assessed as primary outcomes. The outcome measures were monitored daily till the 6th postoperative day. Analyses were performed on 'intention-to-treat' basis, irrespective of compliance. Independent t-test and Chi-square test were used. RESULTS: Of the initial 63 patients, 50 fulfilling criteria were randomized to two groups and assessed over six days yielding 150 patient-days per group. There were no significant baseline differences between groups. The mean daily urine output was significantly lower in the DI bundle group than in control, both overall and among endonasal operated pituitary adenomas [3000.09(462.7) vs. 4095.71(896.4)ml & 2987.14(419.5) vs. 4064.73(1051)ml], with the greatest difference on the second postoperative day. Though hypernatraemia in controls became most prominent during days 2-3 and resolved in a week, it was significantly lower in the intervention group (12.7% vs. 30.7% overall, 11.4% vs. 29.4% endonasal adenomas). The need for vasopressin analogues and hospital stay were also significantly lower with DI bundle (p < 0.001). CONCLUSION: This is probably the first ever report of dietary DI bundle among operated pituitary patients, which seem to flatten the DI trend with significant benefits in polyuria, hypernatraemia, vasopressin requirement and hospital stay. TRIAL REGISTRATION: CTRI/2018/07/015127 of ICMR. IMPACT: The nurse-led dietary DI bundle has effectively reduced the severity of DI among operated pituitary patients with significant benefits in polyuria, hypernatraemia, vasopressin requirement and hospital stay. Its implementation is simple and easy to carry out, especially in resource-constrained institutions, where continuous monitoring and repeated serum sodium estimation are difficult.

Eumycetoma of the Foot due to Fusarium solani in a Person with Diabetes Mellitus: Report of a Case and Review of Literature.

Eumycetomas are chronic suppurative granulomas caused by fungi characterised by invasive tumefactive lesions, sinuses and discharging grains. Herein, we describe a case of pedal eumycetoma due to Fusarium solani sensu stricto in a person with diabetes mellitus. A 45-year-old gentleman presented with an insidious onset swelling over his right foot with nodules and discharging grains. He had received itraconazole and anti-tuberculous therapy elsewhere, without response. Re-evaluation included a biopsy which confirmed eumycetoma and newly diagnosed diabetes. Surgical excision followed by histopathological, microbiological and multigene sequencing analyses [translation elongation factor, calmodulin and internal transcribed spacer region of rDNA] of the mould on culture were performed. Histopathology revealed septate fungal hyphae amidst a dense inflammatory infiltrate (Splendore-Hoeppli) reaction. Oral voriconazole was started and good glycemic control attained. Tissue growth sequences showed > 99% similarity with Fusarium solani sensu stricto. Antifungal susceptibility testing showed lowest MIC to voriconazole (0.5 mg/L). The patient showed excellent response to combined therapeutic modality with a near-complete resolution in size of lesion and obliteration of sinuses following 4 months of therapy and is planned for prolonged voriconazole therapy till complete radiological resolution. Diabetes predisposes to fungal infections of foot but eumycetomas are uncommon. Combined surgery and antifungals can improve morbidity and avoid amputations.

Metformin upregulates mitophagy in patients with T2DM: A randomized placebo-controlled study.

Impaired mitochondrial autophagy (mitophagy) and NLRP3 inflammasome activation have been incriminated in the pathogenesis of T2DM. Metformin besides being an insulin sensitizer also induces autophagy; however, its effect on mitophagy and NLRP3 activation in patients with T2DM still remains elusive. Forty-five drug-naïve T2DM patients with HbA1C 7%-9% (53-75 mmol/mol) were randomly assigned to receive either metformin, voglibose, or placebo for 3 months, and were also recommended for lifestyle intervention programme (n = 15 each). Mitochondrial oxidative stress (MOS) parameters, qPCR and immunoblotting of mitophagy-related markers (PINK1, PARKIN, MFN2, NIX, LC3-II, LAMP2), p-AMPKα (T172), and NLRP3 proteins, as well as transmission electron microscopy (TEM) for assessing mitochondrial morphology were performed in the mononuclear cells of study patients. Both metformin and voglibose showed a similar efficacy towards the reduction in HbA1c and MOS indices. However, multivariate ANCOVA divulged that mRNA and protein expression of mitophagy markers, NLRP3 and p-AMPKα (T172), were significantly increased only with metformin therapy. Moreover, PINK1 expression displayed a significant positive association with HOMA-ß indices, and TEM studies further confirmed reduced distortions in mitochondrial morphology in the metformin group only. Our observations underscore that metformin upregulates mitophagy and subsequently ameliorates the altered mitochondrial morphology and function, independent of its glucose-lowering effect. Further, restoration of normal mitochondrial phenotype may improve cellular function, including ß-cells, which may prevent further worsening of hyperglycaemia in patients with T2DM.

Intracranial Germinoma Masquerading as Secondary Granulomatous Hypophysitis: A Case Report and Review of Literature.

Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.

ACTH increment post total bilateral adrenalectomy for Cushing's disease: a consistent biosignature for predicting Nelson's syndrome.

PURPOSE: Nelson's syndrome (NS) is regarded as an aggressive complication of total bilateral adrenalectomy (TBA) for Cushing's disease (CD). This challenge may be addressed by using clinical criteria to guide frequency of neuroimaging to enable timely management of NS and also avoid unnecessary frequent imaging. METHODS: All patients (n = 43) with CD subjected to TBA over 35 years at a tertiary care centre were included. NS was defined as a newly appearing or expanding (> 2 mm) pituitary adenoma with or without ACTH levels exceeding 500 pg/ml. Pre-and post-TBA parameters like clinical symptomatology, cortisol, ACTH and radiology were analysed for the prediction of NS. RESULTS: NS developed in 39.5% (n = 17) patients with a median follow-up of 7 years. Half of them had new appearance, while rest had an expansion of pre-existing pituitary tumour. Majority (90%) had ACTH above 500 pg/ml. On Cox proportional hazards analysis, frequent discriminatory features of protein catabolism (≥ 4) (HR 1.15, CI 0.18, 7.06), proximal myopathy (HR 8.82, CI 1.12, 69.58) and annual ACTH increment of 113 pg/ml (HR 12.56, CI 1.88, 88.76) predicted NS. First post-operative year ACTH indices predicting NS included ACTH rise of 116 pg/ml and absolute ACTH of 142 pg/ml (sensitivity, specificity exceeding 90%). Annual ACTH increment exceeding 113 pg/ml, ≥ 4 discriminatory features and uncontrolled hypertension had the best overall prediction. CONCLUSION: Patients who developed NS had higher rebound rise of ACTH following TBA and a more severe disease phenotype at baseline. Consistent ACTH increment can be used as a marker for predicting the development of NS.

Pendular See-Saw Nystagmus: A Rare Presenting Manifestation of Craniopharyngioma.

Pendular see-saw nystagmus is an extremely rare form of nystagmus characterised by cyclical movement of the eyes with a conjugate torsional component and a disjunctive vertical component. Intorsion and elevation of one eye is accompanied by simultaneous extorsion and depression of the contralateral eye. Most commonly it results from a suprasellar/parasellar mass compressing the meso-diencephalic region. Herein, we report a case of a 5-year-old girl who presented with pendular see-saw nystagmus secondary to a craniopharyngioma. The nystagmus resolved following excision of the lesion.

Parathyridaria percutanea and Subcutaneous Phaeohyphomycosis.

Parathyridaria percutanea is an emerging fungus causing subcutaneous phaeohyphomycoses in renal transplant recipients in India. We identified P. percutanea from a patient with subcutaneous phaeohyphomycosis. From our culture collection, we identified the same fungus from 4 similar patients. We found 5 cases previously described in literature.

Clinical evaluation of 4D MRI in the delineation of gross and internal tumor volumes in comparison with 4DCT.

PURPOSE: To evaluate clinical utility of respiratory-correlated (RC) four-dimensional magnetic resonance imaging (4DMRI) for lung tumor delineation and motion assessment, in comparison with the current clinical standard of 4D computed tomography (4DCT). METHODS AND MATERIALS: A prospective T2-weighted (T2w) RC-4DMRI technique was applied to acquire coronal 4DMRI images for 14 lung cancer patients (16 lesions) during free breathing (FB) under an IRB-approved protocol, together with a breath-hold (BH) T1w 3DMRI and axial 4DMRI. Clinical simulation CT and 4DCT were acquired within 2 h. An internal navigator was applied to trigger amplitude-binned 4DMRI acquisition whereas a bellows or real-time position management (RPM) was used in the 4DCT reconstruction. Six radiation oncologists manually delineated the gross and internal tumor volumes (GTV and ITV) in 399 3D images using programmed clinical workflows under a tumor delineation guideline. The ITV was the union of GTVs within the breathing cycle without margin. Average GTV and motion range were assessed and ITV variation between 4DMRI and 4DCT was evaluated using the Dice similarity index, mean distance agreement (MDA), and volume difference. RESULTS: The mean tumor volume is similar between 4DCT (GTV4DCT  = 1.0, as the reference) and T2w-4DMRI (GTVT2wMR  = 0.97), but smaller in T1w MRI (GTVT1wMR  = 0.76), suggesting possible peripheral edema around the tumor. Average GTV variation within the breathing cycle (22%) in 4DMRI is slightly greater than 4DCT (17%). GTV motion variation (-4 to 12 mm) and ITV variation (∆VITV =-25 to 95%) between 4DCT and 4DMRI are large, confirmed by relatively low ITV similarity (Dice = 0.72 ± 0.11) and large MDA = 2.9 ± 1.5 mm. CONCLUSION: Average GTVs are similar between T2w-4DMRI and 4DCT, but smaller by 25% in T1w BH MRI. Physician training and breathing coaching may be necessary to reduce ITV variability between 4DMRI and 4DCT. Four-dimensional magnetic resonance imaging is a promising and viable technique for clinical lung tumor delineation and motion assessment.

Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study.

PURPOSE: Endocrinal insufficiency caused by vasculotoxic snake envenomation is under-recognized and is mostly confined to a specific geographic area. We conducted a prospective study to determine the prevalence and pattern of pituitary-target gland insufficiencies caused by snake envenomation. MATERIALS AND METHODS: The hormonal evaluation of patients who had suffered from vasculotoxic snake envenomation was done at baseline and at 6 months of follow-up. Those patients with a documented hormonal insufficiency underwent magnetic resonance imaging (MRI) of the hypothalamo-pituitary area. The severity of envenomation was assessed by the acute physiology and chronic health evaluation II (APACHE-II) score, the sepsis-related organ failure assessment (SOFA) score, and the snake bite severity score (SBSS) for all patients. RESULTS: Seventy-six patients were seen during the study period, of which 60 were available for a repeat hormonal evaluation at 6 months, with the majority of patients belonging to the middle age group (mean age, 37.6 ± 14.9 years). The mean lag period at presentation was 32 ± 20 h. Thirty-five patients (46.1%) had coagulopathy, 20 patients (26.3%) had acute kidney injury (AKI), and 8 of 76 patients (10.5%) needed renal replacement therapy (RRT) in the form of hemodialysis. Six patients (out of 41 with vasculotoxic bites) developed chronic hypopituitarism, which was in continuation with the acute hypopituitarism that they developed. Growth hormone and glucocorticoid deficiencies were the most common endocrinopathies observed. The occurrence of hypopituitarism was observed only in patients with a vasculotoxic snake bite (due to Russell's viper); coagulopathy, renal insufficiency, or any of the scoring tools did not predict the occurrence of hypopituitarism. CONCLUSION: Acute asymptomatic and chronic symptomatic or asymptomatic hypopituitarism are important sequelae of viper bite in a small proportion of patients and can occur in the presence of normal pituitary imaging. Routine prospective pituitary hormone screening should be done in all patients within the first 6 months of envenomation by the vasculotoxic snakebite as chronic pituitary dysfunction can often occur in these patients.

Impact of transsphenoidal surgery on asymptomatic cardiomyopathy in patients with acromegaly. A single-blinded study.

BACKGROUND: Patients with acromegaly have 2-3 times the expected mortality rates primarily due to cardiovascular risks. Echocardiographic studies showing improvement of cardiac function following transsphenoidal surgery (TSS) are limited. MATERIALS AND METHODS: All patients with acromegaly underwent preoperative echocardiography and tissue Doppler (Philips i33, 3D ECHO) for assessment of cardiac indices. In the prospective group of patients, echocardiography was repeated after 6 months of surgery. In the retrospective group of patients, echocardiography was performed for left ventricular diastolic dysfunction and ejection fraction. Biochemical cure was confirmed at least after 6 months by glucose-suppressed plasma growth hormone (GH) concentrations (GH-OGTT) of less than 0.4 ng/ml, random GH of less than 1 ng/ml, and normal age-corrected insulin-like growth factor (IGF-1) values. RESULTS: In the prospective group (38 patients), there was a significant decrease in the left ventricular mass (LVM) and LVM index (LVMI) in patients who were cured as well as in patients with postoperative growth hormone (GH) 1-5 ng/ml. In the prospective group, LVMI completely normalized in 2 and a new-onset deterioration was detected in 1 patient (who was not cured) and improved in 8 others. Left ventricular systolic function was abnormal at baseline in 18 (47.3%) patients, which normalized in 11 (61.1%) patients postoperatively, and in 7 patients, it improved significantly although it did not normalize completely. There was also a significant improvement in the left ventricular ejection fraction (P = 0.01). Post TSS, in patients with GH-OGTT >5 ng/ml, there was no significant decrease in the LVM, LVMI and ejection fraction (EF). In the retrospective group, 62 patients were analyzed for a change in the EF with a mean follow-up of 20.3 months. There was a significant improvement in the left ventricular EF in patients who were cured (P < 0.001). CONCLUSION: Reduction in growth hormone levels and insulin-like growth factor type 1 can decrease the LVM and LVMI, which directly or indirectly contributes to the improvement in diastolic as well as systolic function and probably mortality.