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The INDIIGo study aimed to establish normative data for serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in adult Indian males, addressing the paucity of data for the South East Asian population. This cross-sectional study included 1271 healthy males aged 20 to 65.9 years from Chandigarh, India, with measurements obtained using the Roche Elecsys electrochemiluminescence immunoassay (ECLIA). Age-specific normative centile curves were generated using the LMS (Lambda, Mu, Sigma) method. Serum IGF-1 levels declined by 30.1 ng/ml per decade (95% CI − 34.9 to − 25.2; p  < 0.001) and were negatively associated with lower socioeconomic status (− 5.8 ng/ml per class; p  = 0.002), ALT (− 0.6 ng/ml per unit; p  < 0.001), and HbA1c (− 8.2 ng/ml per category; p  = 0.04). Positive correlations were observed with serum T4 (+ 4.5 ng/ml per unit; p  < 0.001) and serum albumin (+ 18.0 ng/ml per g/dL; p  = 0.009). IGFBP-3 levels decreased by 447.8 ng/ml per decade (95% CI − 547.6 to − 348.1; p  < 0.001), with a significant positive association with serum T4 (+ 60.8 ng/ml per unit; p  = 0.025). This study provides age-specific normative data for IGF-1 and IGFBP-3 in Indian males and identifies key factors influencing these biomarkers.

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. 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. 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. 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. ClinicalTrials.gov: NCT03289338.

Abstract 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.

Purpose Melorheostosis, or Leri’s disease, is a rare sclerotic bone disorder characterized by a wax-like appearance due to excess cortical bone formation. It affects both genders equally, with a prevalence of approximately 0.9 cases per million, and typically presents during adolescence. Patients commonly experience pain and functional disability, with the potential for contractures and deformities in chronic cases. Method This retrospective review was based on the institute’s rare metabolic bone disease registry ( www.rarembd.in ). It evaluated the clinical profile, biochemistry, and radiology of patients presented to the institute and incorporated into the registry. This study incorporated subjects presented to this institute between January 2007 and October 2024. Results Among 268 rare metabolic bone disease patients incorporated into the registry, 3 were diagnosed with melorheostosis. All three were female, and their ages at presentation were 25, 27, and 45 years. Presenting symptoms included localized pain and functional impairment. Each case demonstrated distinct radiological variants: one showed the classic candle wax appearance, while others exhibited myositis ossificans-like and endosteal osteoma-like features. Management focused on symptomatic relief with non-steroidal anti-inflammatory drugs and bisphosphonates, with variable responses. Conclusion In our small series, all three patients were female with lower limb involvement, presenting with pain and functional impairment. Each case demonstrated a distinct radiological variant of melorheostosis. Management was symptomatic with variable response. The rarity of melorheostosis underscores the importance of awareness and thorough differential diagnosis in clinical practice.

The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.

Despite the multiple advantages of 25-hydroxyvitamin D (calcifediol or 25(OH)D) compared to cholecalciferol, it is used sparingly. This study was planned to assess the safety and efficacy of supplementing daily 25 µg of calcifediol capsules vis-a-vis 100 µg (4000 IU) of cholecalciferol sachets in apparently healthy individuals with vitamin D deficiency in Chandigarh, India (latitude 30.7° North, 76.8° East). It was a prospective, interventional study to evaluate the effects of calcifediol vis-a-vis cholecalciferol. Following initial screening of 70 subjects in each group, 62 were included in the calcifediol and 41 in the cholecalciferol group. Forty-six from calcifediol and 37 from cholecalciferol group completed the 6-month follow up. There was a significant increase in serum 25(OH)D (355% in cholecalciferol & 574% in calcifediol groups, respectively, p < 0.001) and 1,25 (OH)2D (p < 0.001) with a marked decrease in iPTH (p < 0.001) and ALP (p = 0.016) in both groups. Though serum ALP decreased significantly more in the calcifediol group than the cholecalciferol group, no appreciable difference in other biochemical parameters was noted between the groups. No episodes of hypercalcaemia or incidence of new renal stone disease were observed during follow-up. However, hypercalciuria (spot urine calcium creatinine > 0.2 mg/mg) was noted in 8/46 individuals in the calcifediol group and 5/37 individuals in the cholecalciferol group at final visit with no significant difference between two groups. This study establishes the efficacy and safety of correcting vitamin D deficiency with daily 25 µg calcifediol capsules as an alternative to 4000 IU (100 µg) cholecalciferol sachets.

IntroductionPrimary 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 methodsThis 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.ResultsThe 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.ConclusionsNonsurvivors 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.

Abstract Context Temozolomide (TMZ) is endorsed as the treatment of choice in aggressive or malignant pituitary adenomas. Objective Herein we describe a case of an aggressive prolactinoma that was resistant to TMZ. We performed a literature review of similar nonresponsive, aggressive prolactinomas. Methods A 40-year-old woman presented with a giant prolactinoma that required cabergoline, transsphenoidal surgery, and radiotherapy to achieve near-normal prolactin and apparently no residual tumor. A year later, she presented with multiple cranial nerve involvement due to a recurrent tumor extending to the infratemporal fossa. She underwent transfrontal surgery, second radiotherapy, and was started on TMZ. Despite 8 cycles of temozolomide (200 mg/m2, 5/28-day cycle), she had progressive disease and ultimately succumbed to the disease. PubMed/MEDLINE, Google Scholar, and prior review articles were searched for manuscripts about patients with aggressive prolactinomas who had been treated with TMZ. Data on demography, duration of therapy, and management outcomes were analyzed in those with progressive disease. Results We identified 94 cases of patients with aggressive/malignant prolactinomas in the literature who had received TMZ. Progressive disease despite TMZ was present in 36 cases (38%). There was a male preponderance (65%) among these and 40% had aggressive prolactinomas, whereas the rest had carcinomas. Patients received a median of 8 cycles (interquartile range, 3.5-11.5) of TMZ. O6‐methylguanine‐DNA‐methyltransferase (MGMT) immunostaining was negative in 35%. Overall mortality at the time of publication was 40%, at a duration varying from 2 to 20 years from diagnosis. Conclusion TMZ resistance in aggressive/malignant prolactinomas is challenging. Progressive disease on optimal TMZ treatment entails the use of newer agents.