Diagnostic Modalities, Management Considerations, and Outcomes of Insulinoma: A Case Series from a Tertiary Care Centre.

Introduction: Insulinomas are rare, usually sporadic, and typically benign pancreatic neuroendocrine tumours. Pre-operative localization is challenging and evidence on comparative analysis of anatomic and scintigraphic modalities for pre-operative tumour localization is limited, even in contemporary series. Methods: The current study was designed to study the clinical features and management challenges of insulinomas managed at a tertiary care centre. Clinical features, diagnosis, imaging techniques, surgical procedures, and outcomes details were collated. Pre-operative imaging techniques (CT/MRI, nuclear scintigraphy) were compared with intraoperative and histopathological findings to assess their accuracy of localization. Results: Thirty-seven patients (15 females [42%]; median age 36 years [IQR 28-49]) were included in the study. In four patients (10.8%), the tumour occurred in the setting of multiple endocrine neoplasia type 1 (MEN 1) while the remaining were sporadic. The sensitivity of pre-operative localization was 61.5% (multiphasic CT), 66.6% (multiphasic MRI), 100% (68Ga Exendin-4 PET-CT), and 91.6% (EUS). Three patients with normal multiphasic CT had localization on 68Ga Exendin-4 PET-CT. The positive predictive value (PPV) of both Exendin-PET-CT and EUS was similar at 91.6% and 91.6%, respectively. All patients (except one with nesidioblastosis), who underwent enucleation or partial pancreatic resection, were cured. Conclusion: 68Ga Exendin-4 PET-CT based is a non-invasive imaging modality that has high sensitivity and PPV and can be used as a first-line imaging modality. The overall prognosis of these tumours is good with high cure rates attained following surgical resection.

Comprehensive safety profile of dipeptidyl peptidase-4 inhibitors: a post-marketing study based on FAERS database using signal detection algorithms.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) have acquired a foothold in managing type 2 diabetes mellitus, but few concerns have arisen regarding their overall safety profile. The aim of this study is to assess the potential risk of DPP-4 inhibitors by analyzing data from the FDA Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: This is a retrospective study which explored the FAERS database till March 2023 for the collection of safety reports. The disproportionality analysis was performed using signal detection algorithms (SDAs) incorporating frequentist-based data mining approach such as relative reporting ratio (RRR), reporting odds ratio (ROR) and proportional reporting ratio (PRR) with 95% confidence interval (CI). RESULTS: A total of 14,573 adverse event reports were reported in the FAERS public dashboard associated with all the included DPP-4 inhibitors. The computed PRR, ROR, and RRR indicated positive signals for DPP-4 inhibitors with cardiac failure, pancreatitis, pemphigoid, hypoglycemia, acute kidney injury and lactic acidosis. Saxagliptin showed a higher signal score for cardiac failure, while sitagliptin was more associated with pancreatitis. Moreover, alogliptin exhibited an elevated signal score associated with pancreatic carcinoma. CONCLUSION: Several significant disproportionality signals were observed with DPP-4 inhibitors. However, clinicians have to consider the comorbidities and concomitant drugs while prescribing these drugs.

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.

Transcription Factor Immunohistochemistry in the Classification of Pituitary Neuroendocrine Tumor/Adenoma: Proposal in a Limited-Resource Setting.

CONTEXT.­: Pituitary neuroendocrine tumors/adenomas are common intracranial tumors that require accurate subtyping because each tumor differs in its biologic behavior and response to treatment. Pituitary-specific transcription factors allow for improved lineage identification and diagnosis of newly introduced variants. OBJECTIVE.­: To assess the usefulness of transcription factors and design a limited panel of immunostains for classification of pituitary neuroendocrine tumors/adenoma. DESIGN.­: A total of 356 tumors were classified as per expression of pituitary hormones and transcription factors T-box family member TBX19 (TPIT), pituitary-specific POU-class homeodomain (PIT1), and steroidogenic factor-1 (SF-1). The resultant classification was correlated with patients' clinical and biochemical features. The performance and relevance of individual immunostains were analyzed. RESULTS.­: Reclassification of 34.8% (124 of 356) of pituitary neuroendocrine tumors/adenoma was done after application of transcription factors. The highest agreement with final diagnosis was seen using a combination of hormone and transcription factors. SF-1 had higher sensitivity, specificity, and predictive value compared with follicle-stimulating hormone and luteinizing hormone. On the other hand, TPIT and PIT1 had similar performance and Allred scores compared with their respective hormones. CONCLUSIONS.­: SF-1 and PIT1 should be included in the routine panel for guiding the classification. PIT1 positivity needs to be followed by hormone immunohistochemistry, especially in nonfunctional cases. TPIT and adrenocorticotropin can be used interchangeably as per availability of the lab.

Sellar Suprasellar Surprise: A Rare Case of Atypical Teratoid/Rhabdoid Tumor in an Infant.

We present a case of a 10-month-old male infant who initially presented with polyuria, polydipsia, drowsiness, and fever. Neuroimaging using non-contrast computed tomography (NCCT) demonstrated obstructive hydrocephalus associated with a suprasellar mass, for which emergency neurosurgical intervention was performed with right parietal medium pressure ventriculoperitoneal (MPVP) shunting. For fever, no cause was found with sterile cerebrospinal fluid (CSF) analysis, and empirical antibiotics were administered. The patient exhibited polyuria with hypernatremia and was diagnosed with arginine vasopressin (AVP) deficiency, further complicated by visual impairment due to left optic atrophy. Hormonal workup revealed secondary hypothyroidism and hypocortisolism. Imaging by contrast-enhanced magnetic resonance imaging (CEMR) revealed a lobulated solid-cystic suprasellar mass with flow void, suggestive of adamantinomatous craniopharyngioma initially. However, despite multiple neurosurgical interventions, the patient's condition deteriorated with recurrent fever and seizures, leading to a revision of ventriculoperitoneal shunts. Repeat CEMR showed an increase in the size of the lesion with spinal leptomeningeal metastasis, suggesting a different pathology. Transventricular biopsy confirmed an atypical teratoid and rhabdoid tumor (AT/RT), World Health Organization Classification of Tumors of the Central Nervous System (CNS WHO) grade 4, characterized by diffuse growth pattern, moderate nuclear pleomorphism, clear cytoplasm, and prominent nucleoli. Immunohistochemistry revealed positive vimentin staining and loss of integrase interactor 1 (INI1) expression, consistent with AT/RT. The patient's parents were counseled on the need for multimodal management, including surgery and chemotherapy. However, due to socioeconomic constraints and a guarded prognosis, they chose to leave against medical advice. This case illustrates the diagnostic challenges in distinguishing AT/RT from other suprasellar masses and emphasizes the importance of a multidisciplinary approach in managing complex pediatric cases.

A Rare Case of Headache in a Patient With McCune-Albright Syndrome: A Triple Threat.

A 26-year-old male presented with facial asymmetry since 11 years of age and painless progressive diminution of vision in the left eye since 16 years of age. He presented with an exacerbation of headaches for the past two months. On examination, he was tall and had acral enlargement, craniofacial deformity, and bilateral asymmetric testicular enlargement. Investigations revealed high insulin-like growth factor 1, non-suppressible growth hormone on oral glucose tolerance tests, and multiple pituitary hormone deficiencies. MRI showed pituitary macroadenoma with craniofacial and sphenoid fibrous dysplasia as well as multiple tuberculomas. Cerebrospinal fluid testing showed high protein, low glucose, and high adenosine deaminase, all consistent with a diagnosis of central nervous system (CNS) tuberculosis. His headache did not respond significantly to either octreotide or zoledronic acid. The patient was then initiated on antitubercular therapy, which led to near-complete resolution of the headache and CNS lesions within three months of therapy. CNS tuberculosis was a masquerader in the index case of acrogigantism due to McCune-Albright syndrome. Headaches may be multifactorial in a given case of acromegaly, and investigating for alternative or additional causes especially when dealing with treatment-refractory cases can be rewarding.

Unusual and lesser-known rare causes of adult growth hormone deficiency.

Growth hormone is among the most common hormones to be deficient in pituitary insult. It can occur either in isolation or combined with other hormone deficiencies. Growth hormone deficiency in adults (AGHD) can be due to causes acquired in adulthood or have a childhood-onset etiology, but the former is about three times more common. Usual causes of AGHD include mass effects due to a pituitary tumour, and/or its treatment (surgery, medical therapy, or radiotherapy), or radiotherapy to the head and neck region for non-pituitary lesions. The unusual or lesser-known causes of AGHD, are usually due to non-tumoral etiology and range from vascular and infective to inflammatory and miscellaneous causes. These not only expand the spectrum of AGHD but may also contribute to increased morbidity, adverse metabolic consequences, and mortality due to the primary condition, if unrecognised. The review features these lesser-known and rare causes of AGHD and highlights their clinical and diagnostic implications.

Diagnostic utility of procalcitonin for bacterial infections in diabetic ketoacidosis.

Procalcitonin is a widely used infection biomarker; however, its utility in identifying bacterial infection in diabetic ketoacidosis (DKA) is unclear. We aimed to evaluate its diagnostic performance for detecting DKA cases triggered by bacterial infections. We reviewed 303 case records of patients aged ≥ 13 years with DKA admitted to the emergency department, PGIMER (Chandigarh), between 2017 and 2022. Baseline procalcitonin was measured by electrochemiluminescence immunoassay, and a value > 0.5 ng/mL was considered elevated. Both microbiological reference standard (MRS) and composite reference standard (CRS) were used to evaluate the diagnostic performance of procalcitonin. 151/303 (49.8%) DKA cases had infection precipitations. Bacterial infections were present in 98 patients (53 microbiologically confirmed), of which urinary tract infection (n = 42), pneumonia (n = 19), skin and soft-tissue infection (n = 13), and bacteremia (n = 11) were common. The median value of procalcitonin was higher with bacterial infections than in patients without (3.68 vs. 1.00, P-value < 0.001). An elevated procalcitonin to detect bacterial infections in DKA had sensitivity 84.69%, specificity 34.15%, positive likelihood ratio (LR +) 1.29, and negative likelihood ratio (LR -) 2.44, against CRS. Against MRS, both LR + and LR - further decreased to 1.23 and 1.81, respectively. Using the receiver-operating-characteristic curve, an optimal cut-off of procalcitonin was calculated at 1.775 ng/ml against both CRS (area under curve 0.655, sensitivity 68.37%, specificity 59.02%, LR + 1.67, LR - 1.86, Yoden's index 0.274) and MRS (area under curve 0.616, sensitivity 67.92%, specificity 59.02%, LR + 1.66, LR - 1.84, Yoden's index 0.269). Procalcitonin does not help detect bacterial infections in patients with DKA at admission.

Impulse Control Disorders with Short-term Use of Cabergoline in Macroprolactinomas: A Prospective Study with a Brief Review of Literature.

Impulse control disorders (ICDs) are less-emphasized adverse effects of dopamine agonists. Evidence on prevalence and predictors of ICDs in patients with prolactinomas is limited and confined chiefly to cross-sectional studies. This was a prospective study performed to investigate ICDs in treatment-naïve patients with macroprolactinomas (n = 15) using cabergoline (Group I), compared to consecutive patients of nonfunctioning pituitary macroadenomas (n = 15) (Group II). Clinical, biochemical, radiological parameters and psychiatric comorbidities were evaluated at baseline. ICD was assessed by Minnesota impulsive disorder interview, modified hypersexuality and punding questionnaires, South Oaks gambling scale, kleptomania symptom assessment scale, Barratt impulsive scale (BIS), and internet addiction scores (IAS) at baseline and 12 weeks. Group I had a significantly lower mean age (28.5 vs. 42.2 years) with a female predominance (60%) compared to group II. Median tumor volume was lower in group I (4.92 vs. 14 cm3) despite significantly longer symptom duration (2.13 vs. 0.80 years) than in group II. Serum prolactin decreased by 86% (P = 0.006) and tumor volume decreased by 56% (P = 0.004) at 12 weeks in group I, with a mean weekly cabergoline dose of 0.40 ± 0.13 mg. There was no difference between both groups in hypersexuality, gambling, punding, and kleptomania symptom assessment scale scores at baseline and 12 weeks. Mean BIS showed a more remarkable change in group I (16.2% vs. 8.4%, P = 0.051), and 38.5% of patients transitioned from average to above-average IAS in group I. The current study found no increased risk of ICD with short-term use of cabergoline in patients with macroprolactinomas. The use of age-appropriate scores (such as IAS in younger individuals) may help diagnose subtle alterations in impulsivity.

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

PURPOSE: The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. METHODS: It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). RESULTS: Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. CONCLUSION: Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

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.

Approach to the Patient: A Case With an Unusual Cause of Hypopituitarism.

Hypopituitarism, which refers to insufficiency of one or more hormones of the pituitary, can be due to myriad causes. The clinical and radiological spectrum of the condition is heterogeneous, based on the patient's age, gender, clinical setting, and/or other past medical history. Hypopituitarism includes central hypocortisolism, hypothyroidism, hypogonadism, and growth hormone deficiency. Both hypo- and hyperprolactinemia can be associated with hypopituitarism, with low prolactin signifying more extensive pituitary damage. Posterior pituitary insufficiency (arginine vasopressin deficiency) occurs either in isolation or with anterior pituitary hormone deficiency. Clinical symptomatology of hypopituitarism is usually nonspecific and insidious in onset and progression. Overall, the most common cause of hypopituitarism is a pituitary adenoma and/or its management (surgery, radiotherapy, pharmacotherapy, or a combination of these). However, it is this subset of patients which is more likely to be identified and managed in a timely manner, possibly alleviating the premature mortality associated with hypopituitarism. What is more challenging is the recognition of hypopituitarism in less common settings, which may be either due to direct involvement of the pituitary (infection, traumatic brain injury, or infiltrative causes) or indirectly as a consequence of the primary process (thalassemia, vasculotoxic snakebite, subarachnoid hemorrhage). These entities are often under-recognized, and increased awareness can help in greater recognition of the burden. Further, pituitary insufficiency in most of these settings is dynamic and may progress, or rarely, show recovery of function. This renders complexity to the problem, but makes it even more imperative to suspect, screen, and appropriately manage patients with less common causes of hypopituitarism.

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.

An audit of medullary thyroid carcinoma from a tertiary care hospital in northwest India.

Introduction: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy originating from parafollicular C cells. It accounts for 5%-10% of all thyroid malignancies. Methods: An ambispective analysis of pathologically proven MTC presented in a tertiary care hospital in northwest India was performed after considering demography, clinical manifestation, RET mutation status, management, and outcome as denominators. Results: Among 2,735 thyroid malignancy cases who presented to our institute in the last 10 years (2012-2022), 78 (3%) had MTC with a mean age of presentation of 43 ± 11 years; 60% of them were female. The median duration of symptoms was 23 months (IQR 12-36 months). The most common presenting complaint was goiter with lymphadenopathy (80.8%). Among the atypical presentations, one each had ectopic Cushing's syndrome, hypertensive crisis in pregnancy due to pheochromocytoma, synchronous chondrosarcoma, and Von Hippel-Lindau disease spectrum. Median calcitonin and carcinoembryonic antigen (CEA) levels at presentation were 1,274 pg/mL (n = 64) and 149 ng/mL (n = 39), respectively. Twenty-two patients were germline RET mutation-positive, and they presented at a younger age. Majority of the patients presented with stage IV disease. Surgery was the primary modality of therapy. Twenty-nine patients received radiotherapy and 25 patients received tyrosine kinase inhibitors (TKIs). Nine patients received peptide receptor radiotherapy (PRRT) with Lu-177 with neoadjuvant capecitabine. Median progression-free survival (PFS) was 60 months. Patients without structurally and biochemically residual disease and stable disease after the first modality of therapy (Log-rank 11.4; p = 0.004) had a better PFS. Female patients (Log-rank: 9.5; p = 0.002) had a better PFS than male patients. Conclusion: This study showed that MTC comprises 3% of thyroid malignancies with a female preponderance. RET mutation-positive patients had a younger age at presentation. Surgery was the first-line therapy. Radiotherapy, TKI, and PRRT were given as a part of second-line or third-line therapy due to persistent disease and/or disease recurrence. The median PFS was better in female patients and in patients who had no residual lesions and stable disease after the primary modality of therapy.

Multifocal Multisystem Langerhans Cell Histiocytosis Involving Pituitary Masquerading as Crohn's Disease: A Case Report and Review of the Literature.

Background/Objective. We present a case of Langerhans cell histiocytosis (LCH) with gastrointestinal involvement masquerading as inflammatory bowel disease (IBD) in a patient who initially had features of central diabetes insipidus (CDI). Case Report. A 19-year-old male presented at 14 years of age with central diabetes insipidus. He subsequently developed panhypopituitarism and sellar-suprasellar mass, the biopsy of which was inconclusive. Secondary causes for hypophysitis were ruled out. Five years later, he developed perianal pus discharging sinuses, positive ASCA, and sacroiliitis. Rectal ulcer biopsy showed nonspecific inflammation and necrosis. Hence, he was managed as inflammatory bowel disease (IBD). Due to nonresponsiveness of symptoms, doubt about diagnosis was invoked and rectal ulcer biopsy was repeated, which then showed infiltration by Langerhans cells. Hence, he was diagnosed with LCH and showed resolution of symptoms on initiating steroids and vinblastine. Discussion. Gastrointestinal involvement by LCH is unusual and only rarely has represented a prominent clinical manifestation. In most cases, such involvement suggests widespread multisystem disease. Its distinctive morphologic and immunohistochemical features allow LCH to be distinguished from other inflammatory infiltrations found in mucosal biopsy specimens. Conclusion. Preceding CDI and hypopituitarism may predict LCH in patients with IBD-like diseases.

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.

Phosphorylation of ß-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the ß-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, ß-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of ß-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.

Camurati-Engelmann Disease Complicated by Hypopituitarism: Management Challenges and Literature Review of Outcomes With Bisphosphonates.

Background: Camurati-Engelmann disease (CED) is a rare bone dysplasia characterized by diffuse diaphyseal osteosclerosis. Skull base involvement in CED can result in hypopituitarism but is seldom reported. Our objective was to report a patient with acquired hypopituitarism due to CED and assess the management challenges. Case Report: A 20-year-old boy presented with lower limb pain. He had walking difficulty in childhood, which was diagnosed as CED and managed with prednisolone. He later discontinued treatment and was lost to follow-up. Current re-evaluation showed short stature (-3.6 standard deviation), low weight (-4.3 standard deviation), and delayed puberty with delayed bone age (13 years). He was found to have secondary hypogonadism (luteinizing hormone level, 0.1 mIU/mL [1.7-8.6 mIU/mL]; follicle-stimulating hormone level, 1.0 mIU/mL [1.5-12.4 mIU/mL]; and testosterone level, 0.087 nmol/L [9-27 nmol/L]), growth hormone deficiency (low insulin-like growth factor I level, 120 ng/mL [226-903 ng/mL] and peak growth hormone level of 7 ng/mL on insulin-induced hypoglycemia), and secondary hypocortisolism (cortisol level, 105 nmol/L [170-550 nmol/L] and adrenocorticotropic hormone level, 6 pg/mL [5-65 pg/mL]). Serum prolactin level was normal (8.3 ng/mL [5-20 ng/mL]), and he was euthyroid on levothyroxine replacement. Magnetic resonance imaging revealed a partially empty sella. Sanger sequencing revealed a missense mutation (p.R218C/c.652C>T) in exon 4 of the TGFß1 gene. The patient was treated with zoledronate, losartan, and oral prednisolone and continued on levothyroxine and testosterone replacement, which resulted in symptomatic improvement. Discussion: The index case manifested severe CED requiring multimodality therapy. Later, he developed combined pituitary hormone deficiencies, which were managed with thyroid and gonadal hormone replacement with the continuation of glucocorticoids. The partial efficacy of bisphosphonates in CED has been reported in the literature. Conclusion: Skull base involvement in CED can lead to structural and functional hypopituitarism as a result of intracranial hypertension.