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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. 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. 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. 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.

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.

Wolfram syndrome (WFS) is a rare, monogenic neurodegenerative syndrome characterised by insulin requiring non-autoimmune diabetes mellitus (DM) and optic atrophy which are usually the earliest and commonest manifestations. However, there are other features which are under-recognized, adding to morbidity and premature mortality in these patients. Five patients (three males, two females) with genetically confirmed WFS at a single tertiary care centre were prospectively followed up. Their symptomatology, clinical profile, genetic analysis and radiology were analyzed. Multidisciplinary approach was used for comprehensive clinical care of this cohort. Patients with primary gonadal failure were subjected to biopsy and immunohistochemistry (IHC) for wolframin was performed. DM was the earliest presenting manifestation at 6.2 ± 1.3 years followed by optic atrophy at 10.4 ± 2.3 years, diabetes insipidus at 12 ± 2.1 years and deafness at 12.8 ± 2.1 years. All patients were autoantibody negative with low C-peptide(

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 TGFβ1 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. ispartof: AACE Clin Case Rep vol:8 issue:2 pages:58-64 ispartof: location:United States status: Published online

IntroductionEvidence on new-onset endocrine dysfunction and identifying whether the degree of this dysfunction is associated with the severity of disease in patients with COVID-19 is scarce.Patients and MethodsConsecutive patients enrolled at PGIMER Chandigarh were stratified on the basis of disease severity as group I (moderate-to-severe disease including oxygen saturation 94% and without comorbidities) (n=49). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes, and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed.ResultsPatients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% of patients without significant difference between both groups.ConclusionCOVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease.

Pheochromocytoma during pregnancy is a rare cause of secondary hypertension with lethal consequences to both mother and fetus. As patients are young, the possibility of syndromic associations like MEN-2, VHL, NF-1, etc., needs to be considered. Three primigravida were diagnosed before the 20th week of gestation when they presented with classical triad of pheochromocytoma. Diagnosis of pheochromocytoma was confirmed by 24 h urinary metanephrine/normetanephrine or epinephrine/norepinephrine levels. Non-contrast MRI abdomen could localize the tumor. One patient had medullary thyroid carcinoma with hyperparathyroidism, indicative of MEN-2A. Another patient had brain stem hemangioblastoma, pancreatic cysts and family history of spinal hemangioblastoma, so diagnosed to have Von Hippel-Lindau (VHL) syndrome. Whereas, the third patient had sporadic pheochromocytoma. Preoperatively, they required antihypertensive medications including prazosin and metoprolol. They underwent laparoscopic/open adrenalectomy between 19th and 21st week of gestation without complication. Histopathology in all the three patients revealed low-grade pheochromocytoma by pheochromocytoma of the adrenal gland scaled score. None required antihypertensive medications after surgery. All the three newborns were small for gestational age, while one neonate expired due to intra-cardiac rhabdomyoma. So, the timely evaluation and surgical intervention for pheochromocytoma avoid lethal consequences. Pregnancy leads to unmasking of pheochromocytoma as it is physiological stress. The syndromic association is more frequent as the population is younger. A poor fetal outcome like IUGR can be explained by endovascular changes in uterine vessel or due to the associated manifestations of MEN-2A, VHL syndromes. Family members should be screened for associated syndromic feature.

Objective To analyze pregnancy course and outcomes in women treated for acromegaly and compare outcomes based on disease activity at the time of conception. Design Retrospective study. Patients Women with acromegaly diagnosed prior to or during pregnancy from 2010 to 2019, representing cases (14 pregnancies in 12 cases), were later stratified based on active (n = 5) or controlled disease (n = 9) at time of conception. Female acromegalic patients over the same period constituted the ‘acromegaly cohort’ (AC) (n = 75). Results All cases had macroadenomas with nadir GH of 15.06 ng/ml (IQR 9–30), IGF-I index of 3.04 (1.96–3.82), for which they had undergone pituitary surgery; except two patients diagnosed during pregnancy, who received pharmacotherapy followed by surgery 4 months postpartum. Adjuvant pharmacotherapy was required in 71.4% patients and radiotherapy in 35.7%. Pregnancy occurred at a median of 2 (0.8–5.1) years after surgery and 21.4% required assisted reproduction. All had term delivery with normal APGAR except one case with gestational hypertension, who delivered a preterm baby. None had congenital malformations. Despite higher baseline IGF-I, GH and tumor volume in those with pre-conceptional active acromegaly, materno-fetal outcomes were not different from those with controlled disease (p > 0.05). Similar or greater proportion of cases had normal GH and no residual tumor postpartum, even in those with pre-conceptional active acromegaly. Conclusion The current study showed conducive outcomes of gestation in women treated for acromegaly and no higher rates of pregnancy parameters or complications than non-acromegaly pregnancies in the same population. Active acromegaly does not seem to have an adverse bearing on outcomes.

Aims Inflammatory osteolysis is sine-qua-non of active Charcot neuroarthropathy (CN) causing decreased foot bone mineral density (BMD) and fractures. We aimed to explore the effect of anti-inflammatory or anti-resorptive agents for effect on foot bone mineral content (BMC) and consequent long-term outcomes of foot deformities, fractures and amputation. Methods Forty-three patients with active CN (temperature difference >2°C from normal foot) were evaluated. Patients were off-loaded with total contact cast and randomized to receive either methylprednisolone (1gm) (group A), zoledronate (5mg) (group B) or placebo (100ml normal saline) (group C) once monthly infusion for three consecutive months. Change in foot BMC was assessed at 6 months or at remission and followed subsequently up to 4 years for the incidence of new-onset fracture, deformities, or CN recurrence. Results Thirty-six participants (24 male, 12 female) were randomized (11 in group A, 12 group B, 13 group C). The mean age was 57.7± 9.9 years, duration of diabetes 12.3± 5.8 years and symptom duration 6.5± 2.8 weeks. BMC increased by 36% with zoledronate (p = 0.02) but reduced by 13% with methylprednisolone (p = 0.03) and 9% (p = 0.09) with placebo at remission. There were no incident foot fractures, however, two patients sustained ulcers, and 3 had new-onset or worsening deformities and none required amputation during 3.36 ± 0.89 years of follow-up. Conclusion Bisphosphonate for active CN is associated with an increase in foot bone mineral content as compared to decrease with steroids or total contact cast but long-term outcomes of foot deformities, ulceration and amputation are similar. Trial registration ClinicalTrials.gov: NCT03289338.

Objective Posterior pituitary tumours (PPTs) are rare neoplasms with the four recognised subtypes unified by thyroid transcription factor -1 (TTF-1) expression, according to the 2017 WHO classification. Though traditionally defined as low-grade neoplasms, a substantial proportion of them show recurrence/persistence following surgery. Methods We selected patients with PPTs in our cohort of 1760 patients operated for pituitary tumours over the past 10 years (2010–2019). The clinical, radiological, hormonal, histopathological profiles and long-term outcomes of the three cases identified (two pituicytomas and one spindle cell oncocytoma, SCO) were analysed. Following a literature review, data of all published cases with documented TTF-1 positive pituicytomas and SCOs were analysed to determine the predictors of recurrence/persistence in these tumours. Results Patients presented with compressive features or hypogonadism. Two had sellar-suprasellar masses. One had a purely suprasellar mass with a pre-operative radiological suspicion of pituicytoma. Two were operated by transsphenoidal surgery and one transcranially guided by neuronavigation. Histopathology confirmed spindle cells in a storiform arrangement and low Ki67 index. Immunohistochemistry showed positive TTF-1, S-100 expression and variable positivity for EMA, vimentin and GFAP. Re-evaluation showed recurrence/persistence in two patients. A literature review of recurrent/persistent pituicytoma (n = 17) and SCO (n = 9) cases revealed clinical clues (headache for pituicytomas, male gender for SCO), baseline tumour size (≥20.5 mm with sensitivity exceeding 80%) and longer follow-up duration as determinants of recurrence/persistence. Conclusion PPTs are rare sellar masses with quintessential TTF-1 positivity. Recurrent/persistent disease following surgery is determined by greater tumour size at baseline and duration of follow-up. This warrants intensive and long-term surveillance in these patients.

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.

The COVID‐19 pandemic, caused by SARS‐CoV‐2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID‐19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS‐CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL‐6 and CRP in diabetes and obesity can also lead to an enhanced ‘cytokine storm’ in COVID‐19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre‐existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new‐onset organ dysfunction can have deleterious additive effects.

Objective Vasculotoxic envenomation is an uncommon cause of hypopituitarism. Most described cases have varying extent of anterior pituitary dysfunction, but posterior pituitary involvement is extremely rare. Methods Clinical, biochemical, and radiologic evaluation of a young female who presented with secondary amenorrhea was performed. A brief literature review of envenomation-induced hypopituitarism is included. Results A 26-year-old female presented with secondary amenorrhea since the age of 20 years. She had normal stature. Her past medical history was significant for a vasculotoxic snakebite 12 years back requiring hemodialysis, but no hormonal testing was done at that time. Current evaluation showed anterior hypopituitarism. An insulin-induced hypoglycemia test confirmed deficiencies of cortisol and growth hormone axes (peak values 348 nmol/L and 0.03 ng/mL). There was no diabetes insipidus. Magnetic resonance imaging revealed a hypoplastic anterior pituitary with an ectopic posterior pituitary. In view of normal stature and secondary amenorrhea, a diagnosis of envenomation-induced hypopituitarism with ectopic posterior pituitary (EPP) was made. A brief literature review of envenomation-induced hypopituitarism showed both acute and delayed presentation, male predominance, and variable lag period (weeks to years). Nearly half of all patients were asymptomatic. The most common axis involved in acute presentation was the cortisol axis, whereas the thyroid and gonadotroph axes were commonly involved in delayed hypopituitarism. Conclusion Vasculotoxic envenomation is a rare cause of acquired hypopituitarism. EPP in the index case was probably due to the "axonal dieback" phenomenon and subsequent regeneration of the axons at a more caudal site. This case, being the first instance of acquired EPP following envenomation, expands the spectrum of envenomation-induced hypopituitarism. Abbreviations EPP ectopic posterior pituitary HRT hormone replacement therapy

Triple A (Allgrove) syndrome is a rare autosomal recessive disorder characterized by cardinal features of primary adrenal insufficiency (AI) due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrima. It is frequently associated with neurological manifestations such as autonomic dysfunction, cognitive dysfunction, cranial nerve, or motor involvement. Amyotrophy/motor neuron disease is a rare association. We herein report a 19-year-old boy diagnosed with triple A syndrome (TAS), with the classic triad of ACTH-resistant adrenal insufficiency, achalasia, and alacrima. Additionally, he had distal spinal muscle amyotrophy. Alacrima was the earliest feature evident in early childhood, followed by achalasia at 12 years of age. He was diagnosed with AI at the age of 19 years, with involvement of the mineralocorticoid axis. Further evaluation showed a neurogenic pattern on electromyography, consistent with a diagnosis of motor neuron disease. A nerve conduction study revealed no significant neuropathy. Genetic analysis confirmed a pathogenic homozygous mutation in the AAAS gene c.43C>A, p.Gln15Lys. He improved with glucocorticoid and mineralocorticoid supplements for AI, and nifedipine for achalasia and artificial tears. He is planned for esophagomyotomy. In any young patient with AI not due to congenital adrenal hyperplasia, Allgrove syndrome should be ruled out. Though mineralocorticoid sparing pattern is classical, it can rarely be involved, as seen in the index case. Various components of the syndrome, as well as amyotrophy and other neurologic features, may present in a metachronous fashion. Hence, a high index of clinical suspicion can aid in early diagnosis and management.

Background Sodium-glucose co-transporter-2 inhibitors are novel antidiabetes drugs that act via inhibition of renal glucose reabsorption. This action causes osmotic diuresis, reduces intravascular volume and is associated with various adverse effects. In the present paper, we describe the first report on the unmasking of underlying polycythemia vera by canagliflozin in a person with Type 2 diabetes mellitus, which was temporally related to the use of the drug. Case report A 51-year-old obese man with Type 2 diabetes was prescribed canagliflozin 100 mg for control of his glycaemia. He presented 6 months later with asymptomatic elevation of his haemogram measurements (haemoglobin: 16.9 g/dl; haematocrit: 55%; red cell number: 8.1 million/mm3 ; total leukocytes: 23010/mm3 ; platelet count: 9.7 *106 /mm3 ). He had no history of smoking, exposure to high altitude or other drugs. Subsequent investigations revealed myeloproliferative neoplasm (polycythemia vera) on trephine biopsy of bone marrow, normal erythropoietin level and JAK2V617F positivity. Because of the possibility that the underlying condition had been unmasked by canagliflozin, the latter was stopped. This led to a remarkable improvement in the man's haematological profile, with no other significant intervention. The man subsequently restarted the drug of his own accord, causing his haematological profile to worsen again and thereby posing a challenge in monitoring of both polycythemia vera as well as diabetes mellitus. Conclusion This report brings to light unmasking of a new adverse effect of sodium-glucose co-transporter-2 inhibitors in clinical practice caused by volume loss, apart from hypotension and falls.

New-onset hyperglycaemia (NOH) in COVID-19 is a clinically and biochemically heterogeneous entity. While the clinical variations range from a predominant pattern of insulin resistance (IR) and β-cell overstimulation to a depleted β-cell reserve phenotype, differences in working definition make NOH biochemically diverse. The American diabetes association (ADA) defines NOH as fasting plasma glucose (FPG) values 100–125 mg/dL and/or glycated hemoglobin (HbA1c) 5.7%–6.4%, without prior evidence of dysglycaemia. However, studies have used FPG≥126 mg/dL or two FPG 100–125 mg/dL and/or single plasma glucose 100–199 mg/dL.1 Over half a dozen viruses are known to be diabetogenic, including enteroviruses, Coxsackie virus, rubella, cytomegalovirus (CMV) and hepatitis C virus (HCV). The basis of this dysglycaemia is either cytolysis or molecular mimicry, resulting in insulinopenic diabetes. Interestingly, certain infections (CMV, HCV) portend a higher risk of T2DM, by exaggerating IR. In the previous SARS epidemic, NOH was identified as an independent risk factor for mortality, even prior to steroids with the persistence of overt diabetes in 10% of patients at 3 years follow-up.2 Genetic similarity and common receptor (ACE2) between SARS-CoV-1 and SARS-CoV-2 suggest that a proportion of patients with NOH in COVID-19 will have persistent hyperglycaemia. IR has been suggested as the central …

A 42-year-old man presented with episodic headaches for the past 2 months, accompanied by palinopsia (visual perseveration). Medical history was significant for sarcoidosis, necessitating prednisolone use for the past 6 months. The patient had normal vitals, fundus and neurologic examination except for a weak right hand grip. MRI of the brain revealed multiple conglomerated brain abscesses in the left occipito-parietal region (figure 1A). Contemplating a tubercular aetiology, anti-tubercular therapy (ATT), levetiracetam and dexamethasone were started. However, after 3 days, the patient became drowsy and developed right-sided hemiparesis. …

Introduction: Evidence pertaining to new-onset endocrine dysfunction in patients with COVID-19 is currently limited and extrapolated from prior SARS epidemics. Further, identifying whether the quantum of this dysfunction is associated with the severity of disease in patients with COVID-19 is unknown. We aimed to to comprehensively explore the prevalence, nature and degree of endocrine dysfunction stratified based on disease severity at a dedicated COVID care centre. Patients and Methods: Consecutive patients enrolled at PGIMER Chandigarh, were stratified on the basis of disease severity as: group I (moderate to severe disease including oxygen saturation 94% and without comorbidities). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed. Results: Patients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% patients, without significant difference between both groups. Conclusion: COVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease. Involvement of multiple axes, particularly at hypothalamo-pituitary level suggests the possibility of hypophysitis as an underlying etiology. We also observed less characterised findings like atypical thyroiditis and normal DHEAS despite secondary hypocortisolism. Follow-up surveillance of these patients at periodic intervals and estimation of anti-pituitary antibodies could be considered to elucidate viral cytopathic effect or inflammation as the major underlying mechanism of endocrine dysfunction.

"Diabetic striatopathy" is characterized by dyskinesias with basal ganglia hyperintensities on neuroimaging. It is usually reported in elderly females with hyperglycemic hyperosmolar state and rare in patients with diabetic ketoacidosis. Here, we report two young males with diabetic ketoacidosis presenting as striatopathy, along with review of literature.

Introduction Spondylo-epi-metaphyseal dysplasia (SEMD) represents a group of osteo-chondrodysplasias characterized by vertebral, epiphyseal as well as metaphyseal abnormalities. Several genes have been identified underlying the different forms. Methodology and results Two relatives (cousins) in a family were found to have disproportionate short stature with clinical and radiological features suggestive of SEMD. Metabolic bone profile was normal including parathyroid hormone and 25(OH)vitamin D3. Exome sequencing revealed a missense mutation (p. T120M) in the von-Willebrand factor A-domain of the Matrilin 3 (MATN3) gene that segregates with the disease in the family. Conclusion We identified a homozygous missense mutation in MATN3, an important structural component of the extracellular matrix of cartilage, as the genetic cause of SEMD in this pedigree. MATN3 mutations have been more commonly associated with multiple epiphyseal dysplasia than SEMD. Recognition of this mutation will aid in enhancing the understanding and expanding the spectrum of this particular skeletal dysplasia., Highlights • SEMD due to Matrilin-3 mutation is rare and needs further characterisation. • Infantile onset of disproportionate dwarfism and progressive bowing of knees and elbows are diagnostic clues. • Absence of extraskeletal features is noteworthy.

Charcot neuroarthropathy (CN) is a complex syndrome affecting people with diabetes and peripheral neuropathy but preserved vascularity. Without early intervention, active CN may have long-term consequences (1). Recent studies suggest the role of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in mediating inflammatory osteolysis by activating the receptor activator of nuclear factor-κB (RANKL-NF-κB) pathway, thus perpetuating bone loss in an insensate foot with active CN (2,3). The goal of treatment in active CN is therefore to curtail the ongoing inflammation and/or osteolysis. Antiresorptive agents to inhibit osteolysis have been used with modest success (4,5), but anti-inflammatory agents have not been evaluated for CN. We studied the efficacy of methylprednisolone (MP) or zoledronic acid (ZA) in comparison with placebo in active CN along with total contact cast (TCC) as the primary modality. Included participants had a clinical diagnosis of active CN (erythematous and swollen) with a foot temperature difference exceeding 2°C by infrared dermal thermometry (FLIR Systems, Inc., Orlando, FL) compared with a similar site on the opposite foot, substantiated by X-ray and/or MRI. Bone turnover markers (BTMs) P1NP and CTX (Elecsys; Roche Diagnostics, Mannheim, Germany) were estimated by electrochemiluminescence …

A 44-year-old man presented with history of slurring of speech, slowness in activities, abnormal posturing of the upper limbs and drooling of saliva from the mouth. He had a 5-yearlong history of compulsive water drinking, consuming 12–15 L of water every day. He was earlier evaluated for the same and found to have low serum sodium (126 mEq/L). Presently, he was admitted at a primary care facility with fever and altered sensorium. He was found to have serum sodium of 94 mEq/L. His sensorium improved with hypertonic saline infusion; however, after a lucid interval of 48 hours, he developed florid extrapyramidal symptoms. Contrast-enhanced MRI brain revealed bilaterally symmetric T2-weighted fluid-attenuated inversion recovery hyperintensity in caudate and lentiform nuclei. A diagnosis of extrapontine myelinolysis with secondary parkinsonism was made. He improved significantly with levodopa therapy. Psychogenic polydipsia is an important cause of hyponatraemia. Overzealous correction of hyponatraemia can be counterproductive.

Objective: Diabetes mellitus confers an increased cardiometabolic risk in affected individuals. Several mechanisms underlie this equation, but endothelial dysfunction has been implicated as the final common pathway by several studies. Endogenous nitric oxide (NO) is one of the principal molecules mediating normal endothelial vasodilation. This study was aimed at ascertaining the effects of smoke and non-smoke tobacco, both of which are commonly used by Indians, on the serum NO levels. Materials and Methods: A total of 208 type 2 diabetic patients attending the diabetes clinic were enrolled in this study. Data on age, gender, smoking, and tobacco chewing were collected, and the serum levels of NO determined using nitrate reductase and Griess Reagent which converts nitrite to a deep purple azo compound. The amount of the azochromophore accurately reflected the amount of NO in the samples. Results: The mean value of serum NO in smokers was 54.92 μmol/L, as compared to 60.60 μmol/L in non-smokers. The mean value of serum NO in tobacco chewers was 57.32 μmol/L and in tobacco non-chewers was 60.61 μmol/L. In this study, a near-significant association was found between the low serum levels of NO in smokers as compared to nonsmokers. But there was no significant association of serum NO levels in tobacco chewers and non-tobacco chewers. Conclusion: In this study, the difference in effects of different forms of nicotine usage on the NO levels was assessed, as it provides an insight into the mechanism of the effects of oral versus inhaled forms of nicotine use. In conclusion, new facts have been elucidated in this study, and to the best of our knowledge, this is the first comparison of smoke and nonsmoke tobacco in relation to the serum levels of NO for estimating the burden of vascular risk with various forms of tobacco use in diabetes.

A 43-year-old woman with a recent history of chemotherapy for breast carcinoma presented to our clinic with complaint of discolouration of fingernails. She was diagnosed with infiltrating ductal carcinoma of the left breast and underwent modified radical mastectomy for the same. A month later, she was started on adriamycin-based, cyclophosphamide-based and paclitaxel-based chemotherapy, and 3 weeks later, she noticed a progressive brownish discolouration of her fingernails beds. On physical examination, she had diffuse brown discolouration of fingernails of both hands, that is, melanonychia (figure …

Background: Inflammation mediates a key role in the pathogenesis of atherosclerosis which is an important cause of ischemic stroke. An elevated erythrocyte sedimentation rate (ESR) may, therefore, be a marker of the extent andor intensity of a general atherosclerotic process and thus a marker for advanced atherosclerosis heralding increased risk of arterial thrombosis leading to ischemic stroke. Materials and Methods: ESR was calculated in ischemic stroke patients by Westergren′s method along with carotid sonography using high resolution 7.5 MHz techniques to find the prevalence of increased carotid intima-media thickness (CIMT) and presence of plaque according to Mannheim Carotid Intima-Media Thickness Consensus. Results: Average value of ESR in all patients was 27.89 ± 9.73 mm/h. A significant association was found between ESR and markers of carotid atherosclerosis, that is, high CIMT of more than 0.8 mm (P < 0.0001) and presence of plaque (P-0.026) in univariate analysis. Also, a significant positive correlation was found between ESR and serum fibrinogen, another inflammatory marker. (r = 0.88, P < 0.0001). Conclusion: The extent of inflammation may reflect in part the propensity of atherosclerotic lesions to lead to clinical disease. Study shows the association of ESR with markers of atherosclerosis confirming the strength of the inflammatory response associated with carotid atherosclerosis and might conceivably carry important prognostic information regarding occurrence of such catastrophic events in future.

Mona Lisa syndrome is the most fascinating of all pregnancy related syndromes. It represents the characteristic idiopathic lower motor neuron facial nerve palsy mainly presenting in third trimester and associated with facial asymmetry caused by protracted and incomplete motor regeneration of the facial nerve. We encountered a pregnant female with idiopathic left facial nerve palsy of initial House-Brackmann Grade VI who on serial monitoring with facial electroneurography was identified as Mona Lisa syndrome.

Kaposi’s sarcoma has emerged from its relative anonymity and is seen more commonly in association with AIDS today. In India, it is a rare condition with very few incidences being reported. A 52 year old heterosexual Human immunodeficiency virus (HIV) positive man presented with multiple painful swellings over the chest and leg with tuberculous lymphadenopathy. Biopsy and immunohistochemistry revealed Kaposi’s sarcoma. The patient was treated with antiretroviral therapy with boosted protease inhibitor regimen, systemic chemotherapy and cryotherapy. He responded remarkably to the treatment with regression of the lesions and improvement of CD4 count.

Wolfram syndrome is a rare monogenic cause of juvenile onset diabetes mellitus. It is a non-autoimmune, insulin-deficient state with concurrent or consequent optic atrophy. Here we depict the case of a 16-year-old young girl afflicted with this condition, who presented with parasuicide on a background of depressive disorder. The aetiology of this presentation was attributable to multiple physical ailments and a genetic predisposition conferred by the disease-causing mutation for which she tested positive. She was managed with intensive insulin therapy and specific psychotherapy. Her case highlights the importance of recognising and addressing these comorbidities associated with Wolfram syndrome, so as to curtail disastrous consequences.

Malignant peripheral nerve sheath tumor (MPNST) is a rare variety of soft-tissue sarcoma of ecto-mesenchymal origin. Various sites have been mentioned, but it is rare in cauda equina. Only five cases of MPNST of cauda equina are reported till date. A 42-year-old male presented with complaints of weakness in lower limbs for last 5 months with bladder and bowel dysfunction. On magnetic resonance imaging, an isointense lesion on T1 and a hyperintense on T2 imaging was found at terminal spinal cord level. The lesion was excised following laminectomy and showed varied cellularity with thin oval, polyhedral and spindle-shaped cells arranged in bundles on microscopic examination suggesting MPNST. MPNST of cauda equina is rare and is associated with Neurofibromatosis Type-1 or radiation exposure, but is rarer without these risk factors. Prognosis is favorable in these cases.

Background: Atherosclerosis is related to various cardiovascular and cerebrovascular events like cerebral infarction. Recurrence of ischemic stroke is specifically related to atherosclerotic load as determined by the presence of carotid atheromatous plaques and its echogenicity. Aim: This study was to evaluate the association of recurrence of stroke with echogenic characteristics of carotid plaque in ischemic stroke patients. Materials and Methods: Carotid sonography using high-resolution 7.5 MHz along with gray-scale technique was done in each ischemic stroke patient to find the occurrence of plaque and its echogenicity according to Mannheim Carotid Intima-Media Thickness Consensus (2004-2006). Followup of patient done to know the recurrence of stroke during 6-month duration and its association with plaque echogenicity. Results: A significant association found between the presence of plaque and known cerebrovascular risk factors. Also significant association found between recurrence of stroke and echolucent character of carotid plaque in bivariate analysis ( P = 0.0028). Conclusions: Recurrence of stroke is related to advanced stage of atherosclerosis that is specified by carotid plaque and its characteristics. It will help us to identify groups of patients at different risk for stroke and planning better strategies to prevent such events.

A 17-year-old girl from a rural part of Uttar Pradesh in India presented with high-grade fever of 2-month duration along with fatigability and weight loss. She had no symptoms of cough, breathlessness, chest pain, headache, backache or multiple swellings over the body. The patient was asymptomatic earlier with no history of chronic cough, fever or haemoptysis. She does have history of contact with her elder brother currently suffering from active pulmonary tuberculosis infection and on antitubercular medications. On examination, the patient was febrile with oral temperature fluctuating from 102°F to 103°F, pulse rate 106/min, blood pressure 110/60 mm Hg and respiratory rate 20 breaths/min with 95% …

Background: Carotid artery intima media thickness reflects the ongoing process of atherosclerosis in the body. The pathologic process occurring in the obese patients in the vascular system is atherosclerosis which is an important cause of ischemic stroke. Body mass index is an indirect measure of obesity in general population. Aim: The study was to assess the role of carotid artery intima media thickness as a marker of atherosclerosis and its relation with body mass index in ischemic stroke patients. Materials and Methods: Body mass index of the all stroke patients was calculated by using formula body mass in kilograms divided by the square of height in meters. The patients were classified in four groups of body mass index according to Indian standards. Carotid sonography was done to assess the common carotid artery intima media thickness in millimeters by using high resolution 7.5 MHz sonography technique. Results: The average Carotid intima media thickness in this study was 9.23mm. There was a significant association found between increasing carotid artery intima media thickness and groups of body mass index (P