BACKGROUND:Differentiating prolactinomas from non-functioning sellar masses causing hyperprolactinemia due to stalk effect is a common diagnostic challenge. While both can result in elevated serum prolactin, accurate discrimination is essential for appropriate management. OBJECTIVE:To determine the upper limit of serum prolactin in non-functioning sellar masses attributable to stalk effect. METHODS:This retrospective study was conducted at a tertiary care center in South India from January 2015 to December 2024. Patients with both non-pituitary sellar masses and pituitary tumors with negative prolactin immunohistochemistry were included. Patients with functioning pituitary adenomas, hyperprolactinemia-inducing drugs, chronic kidney disease, severe hepatic dysfunction, and PCOS were excluded. The primary objective was to determine the upper limit of serum prolactin levels attributable to stalk effect in patients with non-functioning sellar masses. Preoperative serum prolactin levels were measured using a chemiluminescent immunoassay. The 97th percentile value was taken as the upper limit. RESULTS:Of 288 cases of non-functioning sellar masses, 57 met inclusion criteria. Most of them (87.7%, 50/57) were >1 cm, with 68% (39/57) classified as pituitary adenomas-49% (19/39) being gonadotroph adenomas and 41% (16/39) null cell adenomas. Hyperprolactinemia was observed in 32% of patients. The median serum prolactin level was 14.8 ng/mL, and the 97th percentile was 70 ng/ml. No significant correlation was found between tumor size and serum prolactin level (r = 0.13, P = 0.35). Gender did not significantly affect serum prolactin levels. A serum prolactin threshold of 70 ng/mL was identified, above which non-functioning sellar masses are highly unlikely. CONCLUSION:In patients with non-functioning sellar masses, serum prolactin levels rarely exceed 70 ng/ml. This threshold may serve as a useful diagnostic marker to distinguish stalk effect from prolactinomas. Prospective validation in larger cohorts is warranted.

Zoledronate is most effective when bone turnover is elevated, as in postmenopausal women. Individuals with type 2 diabetes mellitus show lesser bone mineral density gains compared to non-diabetes mellitus individuals with zoledronate, and fractures often occur despite preserved bone mineral density. It is unclear whether zoledronate reduces fracture risks in type 2 diabetes mellitus. This study aimed to evaluate skeletal outcomes, including fracture incidence, over 5 years in postmenopausal osteoporotic women with and without type 2 diabetes mellitus. This prospective cohort included postmenopausal women with bone mineral density T-scores of≤-2.5 at the lumbar spine, femoral neck, or hip. Participants were classified as type 2 diabetes mellitus or non-diabetes mellitus. All received annual zoledronate (4 mg), daily calcium (1000 mg), and cholecalciferol (500 IU), with standardized fall-prevention measures. Fracture history was recorded at follow-up visits, and annual spine radiographs were performed to detect morphometric vertebral fractures. Women completing≥5 years of follow up were included in the final analysis. The primary end point was fracture incidence; secondary end points were changes in bone mineral density and bone turnover markers. Of 221 women enrolled, 150 completed 5 years (63 type 2 diabetes mellitus and 87 non-diabetic mellitus; median age 59 y). The baseline bone mineral density was similar, but bone turnover markers were lower in type 2 diabetes mellitus. At a minimum of 60 months follow up, 20 new fractures occurred in 15 women: 8 (12.7%) with type 2 diabetes mellitus and 7 (8.0%) without. The relative risk (RR) was 1.58 (95% confidence interval: 0.60-4.13; p=0.2). Both groups showed comparable bone mineral density improvements. Despite differences in baseline bone turnover, fracture incidence did not differ significantly between postmenopausal women with and without type 2 diabetes mellitus treated with annual zoledronate over a 5-year follow-up. However, the low number of fracture events and wide confidence intervals limit definitive inference.

Abstract Sex reversal in a 46,XX individual is quite uncommon. Typically, this condition involves a translocation of the sex-determining region Y (SRY) gene. However, there are very few cases where the SRY gene is not involved. Our case reinforces the idea that a single gene disorder in the ovarian development pathway can lead to male gonadal development. Additionally, it supports the notion that ovary development is not a passive process. We present a complex case of genital ambiguity that challenges traditional concepts of sexual development. A 1 year 6-month old child exhibited penoscrotal hypospadias and micropenis. Although gonads descended bilaterally, the karyotype report came as 46,XX. Genetic analysis revealed a homozygous 3′ splice site pathogenic variant (c.286 + 1G>A) in intron 4 of the RSPO1 gene, implicating it in testicular differentiation. This case underscores the importance of early genetic diagnosis in predicting the outcomes and guiding counseling for XX male individuals, who may face complications such as hypergonadotropic hypogonadism and infertility. The complexity of sexual development extends beyond the traditional male–female dichotomy, highlighting the role of single-gene mutations in determining phenotypic outcomes.

Sheehan syndrome is a rare form of hypopituitarism that occurs due to pituitary necrosis following severe blood loss and hypotension during or after childbirth. The disease is mostly insidious, diagnosed after several years postpartum. However, acute Sheehan syndrome is a life-threatening pituitary hormone deficiency that occurs within 6 weeks of childbirth, associated with seizures, headache, loss of consciousness, and acute adrenal crisis with refractory hypotension, hyponatremia, and hypoglycemia. We report a rare case of acute Sheehan syndrome following massive postpartum hemorrhage (PPH) and shock necessitating hysterectomy, during an elective Cesarean section for placenta accreta. The woman in her late thirties presented with altered sensorium and generalized seizures on postpartum day 7, when investigations revealed severe hyponatremia. She also had lactational failure and hormonal evaluation showed evidence of panhypopituitarism with involvement of the lactotroph, corticotroph, and thyrotroph axes. MRI showed a small pituitary with central necrosis, confirming pituitary apoplexy. She improved on hydrocortisone and levothyroxine, but self-discontinued steroids at 3 months postpartum. At one year, she remained asymptomatic, and hormonal evaluation confirmed the recovery of the hypothalamic pituitary adrenal axis and lactotroph axes. This case underscores the importance of considering acute Sheehan syndrome in postpartum women with PPH presenting with seizures and hyponatremia and highlights the rare potential for recovery of pituitary function.

Introduction: Paget’s disease of bone (PDB) is rarely encountered in patients with chronic kidney disease (CKD), with limited reports in the literature. The coexistence of these conditions poses significant diagnostic and therapeutic challenges. This case report examines the management of PDB in advanced CKD, where standard bisphosphonate therapy is contraindicated. Case Report: We report a 51-year-old male with CKD stage 5 presenting with bone pain, deformity, and fracture. Imaging and biochemical evaluation confirmed the diagnosis of Paget’s disease. Due to contraindications to bisphosphonates, the patient was treated with denosumab. The patient showed initial symptomatic and biochemical improvement; however, recurred after 4 months, requiring repeated doses. Conclusion: This case suggests that denosumab could be an alternative in advanced CKD with PDB where bisphosphonates are contraindicated. However, clinicians should be aware of limitations such as the paucity of evidence, the potential for recurrence, and the need for careful monitoring of hypocalcemia. Further research is needed to establish long-term safety and efficacy of denosumab in these patients. Keywords: Paget’s disease of bone , chronic kidney disease , denosumab , alkaline phosphatase , bone scintigraphy

Type 2 diabetes mellitus (T2DM) is associated with alterations in bone metabolism, bone strength, and quality. There is limited literature available regarding the effect of diabetes mellitus (DM) on chronic kidney disease-mineral and bone disorder (CKD-MBD). The study aimed to compare bone mineral health in pre-dialysis CKD patients with and without DM. This cross-sectional study included patients with CKD G3-5 (age ≥ 40 years) categorized into CKD-DM or CKD-non-DM(CKD-NDM) groups. Bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA) were assessed using dual-energy X-ray absorptiometry (DXA). Vertebral fractures (VFs) were assessed by lateral dorsolumbar spine radiography. Of 306 CKD patients (n = 153 per group) age was comparable (57.42 ± 9.6 vs. 56.1 ± 9.2 years; p = 0.23), CKD-DM patients had higher body mass index, waist circumference and estimated glomerular filtration rate. After adjusting for confounders, there was no difference in the prevalence of osteoporosis between CKD-DM and CKD-NDM groups (22.9

Background The accurate preoperative localization of parathyroid adenomas is crucial for minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (PHPT). This study assessed the diagnostic performance of four-dimensional computed tomography (4D CT) in detecting parathyroid adenomas, compared with ultrasound (USG) and technetium methoxy isobutyl isonitrile single photon emission computed tomography (99mTc-sestamibi SPECT/CT). Methods We retrospectively analyzed 53 patients with biochemically confirmed PHPT who underwent all three preoperative imaging modalities, followed by parathyroidectomy from January 2020 to January 2025. Imaging findings were validated against intraoperative localization, histopathology, and intraoperative parathyroid hormone (PTH) dynamics. Multi-gland diseases were excluded. Sensitivity, positive predictive value (PPV), and concordance were calculated. Percentage arterial enhancement (PAE) was analyzed as a radiological marker. Results The mean age was 42.7 ± 14.7 years, with 29 (54.7%) women. Forty-nine (88.7%) patients had typical adenomas, three (0.05%) had carcinoma, and one (0.01%) had an atypical adenoma. The majority of lesions (24, 45%) were located in the right inferior parathyroid gland, followed by the left inferior (16, 30%). Overall, preoperative imaging was able to localize 50/53 (94.3%) lesions correctly. 4D CT correctly localized 45 lesions, outperforming USG and 99mTc-sestamibi SPECT/CT by identifying eight and 12 additional lesions, respectively. Sensitivity was highest for 4D CT (88.2%), followed by 99mTc-sestamibi SPECT/CT (82.4%) and USG (72.6%), with all three modalities showing high PPV (>94%). Among small adenomas (<20 mm), 4D CT demonstrated superior detection (21/21, 100%) compared to USG (16/21, 76.2%) and 99mTc-sestamibi SPECT/CT (15/21, 71.4%). Dynamic enhancement patterns on 4D CT distinguished adenomas from mimickers. However, applying a fixed PAE cutoff (128.9%), as previously proposed, yielded limited sensitivity (75%) and specificity (31.6%). Conclusion 4D CT outperformed USG and 99mTc-sestamibi SPECT/CT in localizing parathyroid adenomas in PHPT and was particularly useful when USG or 99mTc-sestamibi SPECT/CT results were inconclusive. While all three modalities showed high positive predictive value, 4D CT localized additional lesions missed by others. Its dynamic contrast patterns effectively differentiated adenomas from mimics. However, the utility of a fixed PAE cutoff was limited by protocol-dependent variability, indicating a need for tailored thresholds.

Sir, Hypothalamic hamartoma (HH) is a rare intracranial lesion of childhood. According to the position of the lesion, hamartomas are divided into either parahypothalamic or intrahypothalamic variety. Parahypothalamic hamartomas are associated with central precocious puberty (CPP) and intrahypothalamic lesions usually present with gelastic epilepsy, often resistant to antiepileptics. The Delalande[1] classification divides HH into four subtypes (Type I–IV) based upon the position and lateral extension. The characteristic endocrine disorder in HH is CPP, which often occurs within the first 3 years of age.[2] Other rarely reported endocrinopathies include central diabetes insipidus (DI), growth hormone (GH) deficiency,[3] and hypogonadotropic hypogonadism. A combination of hypopituitarism and HH can also be found in Pallister–Hall syndrome (PHS). Here, we present an interesting case of HH who had multiple pituitary hormone deficiency. A 14-year-old boy was presented with short stature and delayed puberty. There was no history of consanguinity and similar illness in the family. The boy had a normal perinatal history and birth weight. He attained all the developmental milestones but in a delayed manner. His short stature was recognized in the last 2 years as he was falling short compared to peers in class. He had no headache or visual disturbances or polyuria/polydipsia. He did not have any behavioral abnormality. His height was 135 cm (<3rd centile and -2.75 standard deviation score), and bone age was 11.5 years (Tanner–Whitehouse III method). The mid-parental height was 168 cm. He had a stretched penile length of 3.5 cm, and both testicular volumes were less than 4 ml. He had absent pubic or axillary hair. There was no polydactyly. Detailed ophthalmologic examination including fundus and oto-rhino-laryngeal examination was normal. Routine biochemical examination was unremarkable, but he had central hypothyroidism [free T4 0.39 (0.89–1.76 ng/dL); thyroid-stimulating hormone1.41 (0.5-5.5 μIU/ml)]. He had a normal cortisol response following 1μg adrenocorticotropic hormone-stimulation test. GH and gonadotropin axis were evaluated after achieving euthyroidism. He had low insulin-like growth factor 1 (<25 ng/mL) [normal 57–241 ng/mL] and clonidine stimulation test (150 mcg/m2) revealed peaked GH level less than 1 ng/mL suggesting severe GH deficiency (GH response more than 7–10 ng/mL is normal[4]). Baseline luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was 0.03 mIU/ml, and 0.09 mIU/ml respectively and testosterone was 3.35 ng/dl. Leuprolide stimulation test showed peak LH response as 0.42 mIU/mL confirming hypogonadotropic hypogonadism (LH level of >5–8 mIU/mL after leuprolide stimulation is considered normal[5]). MRI of the hypothalamic-pituitary area showed a nonenhancing, well-defined lesion measuring 10 × 8 × 9 mm, with the signal intensity of gray matter in all sequences suggestive of HH (T1, T1 post contrast and T2) [Figure 1a-c]. Moreover, MRI showed hypoplastic anterior pituitary and absent posterior pituitary bright spot (PPBS) with normal stalk [Figure 1a].Figure 1: T1W noncontrast (a), T1W postcontrast (b), and T2W noncontrast (c) sagittal images showing a well-defined lesion measuring 10 × 8 × 9 mm in the hypothalamus (white arrows), which follows the signal intensity of gray matter in all sequences. No enhancement of the lesion is noted in the contrast study. The hypoplastic anterior pituitary is seen (black arrow) along with the absent posterior pituitary bright spotThe child had recurrent nonprojectile vomiting after taking food. However, extensive workup including upper gastrointestinal endoscopy, ultrasonography of the abdomen, and awake electroencephalogram was normal. The boy had no features of raised intracranial tension. His vomiting was not controlled initially with domperidone and later, the frequency reduced with addition of ondansetron. Vomiting subsided after 6 months, and currently, he is fine without medication. The exact etiology of vomiting remains inconclusive in this case. A repeat MRI after 1 year showed no change in the HH. Currently, he is on levothyroxine supplementation awaiting GH therapy and pubertal induction with testosterone. HH presenting as short stature and delayed puberty is an exceedingly rare association in a non-PHS patient. PHS is an autosomal dominant disease caused by the pathogenic variation in the GLI3 gene,[6] where HH can be associated with pituitary hormonal deficiency. Other prominent features might include the bifid epiglottis, imperforate anus, postaxial polydactyly, genital, and renal abnormalities. The criteria for PHS index case include both HH and central polydactyly.[7] Several researchers have assessed the endocrine manifestations associated with HH recently. Taylor et al.[8] reported that, among 22 HH patients, 17 patients had CPP as the only endocrine manifestation. In a large series of 193 patients of HH, Harrison et al.[2] found that none had delayed puberty. Similarly, Doddamani et al.[9] found that no patient had pituitary deficiency preoperatively, though four patients had CPP including one PHS. Few reports of pituitary hormonal deficiency in HH had been described. A 17-year-old boy with deafness and behavioural abnormality reported by Martin et al.[10] had hypogonadotropic hypogonadism along with GH deficiency. Contrarily, our patient had no behavioral complications or deafness. Rousseau-Nepton et al. described a patient with HH and CPP, which was treated with gonadotrophic releasing hormone (GnRH) analogue in childhood. This patient was later found to have GH deficiency,[3] confirmed twice at 14 and 18 years of age. Another report[11] described a 14-year-old boy with delayed puberty as the first manifestation of HH. GH axis and pituitary imaging were normal in that case. However, we found hypoplastic pituitary and absent PPBS in MRI pituitary of our patient. Though absent PPBS can be seen in 3-5% of patients after 40 years, its absence in younger patients like ours is unusual.[12,13] Our patient did not have DI then, but a long-term follow up is nevertheless warranted. The development of CPP in HH is explained by several mechanisms: 1) HH acting as GnRH pulse generator or 2) secreting transforming growth factor-alpha[14] and 3) critical contact of HH with the tuber cinereum and the infundibulum.[15] However, the explanation for pituitary hormonal deficiency in HH is incompletely understood. The putative theories are: 1) nonpulsatile GnRH secretion suppressing LH release,[10] 2) anatomical compression at the level of arcuate nucleus decreasing GH releasing hormone (GHRH) secretion and thus causing GH deficiency[3] or 3) unrestrained somatostatin secretion inhibiting releasing hormone secretion from the hypothalamus.[3] In our case, due to its location, the hamartoma has the potential to block the transport of the hypothalamic releasing hormones (GHRH, GnRH, TRH) to the anterior pituitary and to disrupt the intrahypothalamic neuronal connections, resulting in decreased secretion of hypothalamic hormones. HH can be associated with multiple pituitary hormone deficiency without any features of PHS. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Disclosure: S. Giri: None. S. Kamalanathan: None. R. Govindarajalou: None. D. Naik: None. S. Ali Mondal: None. J. Sahoo: None. Introduction: Zoledronate is primarily beneficial when bone turnover is elevated, such as in the postmenopausal state. The gain in bone mineral density (BMD) is significantly lower in subjects with diabetes mellitus (DM) compared to non-DM subjects due to lower baseline bone turnover in diabetes. Moreover, fractures occur at relatively preserved BMD in DM, making neither BMD nor bone turnover markers (BTMs) reliable for assessing bone health. Few studies have shown that zoledronate increases BMD in DM as well. However, whether this translates to fracture prevention remains unclear. No prospective study has compared its efficacy in terms of fracture outcomes in patients with and without DM. Aims: To assess the effect of zoledronate on major osteoporotic fractures in postmenopausal osteoporotic women with and without diabetes over 5 years. Methods: This prospective cohort study involved postmenopausal women with BMD T-scores of – 2.5 or lower at any site among the femoral neck, hip or, lumbar spine. Participants were divided into two groups: 1) with type 2 DM and 2) without DM. Both groups received annual intravenous zoledronate (4 mg), along with daily 25-hydroxyvitamin D (500 IU) and calcium (1000 mg) orally. A fall prevention template was also provided. Fracture history was documented at each visit, and lateral radiographs of the thoracic and lumbar spine were taken at baseline and annually to detect morphometric vertebral fractures using semi-quantitative method introduced by Genant et al. Women who completed at least 5 years of follow-up were analyzed. The primary endpoint was the number of participants in each group developing new major osteoporotic fractures, including morphometric vertebral and fragility fractures. Secondary endpoints included changes in BMD and BTMs. Results: Initially, 183 women were recruited for the study; among them, 150 women, with a median age of 59 years and a post-menopausal duration of 10 years, completed the study. Of these, 63 had DM and 87 did not. The median diabetes duration was 8 years and mean glycated hemoglobin A1c (HbA1c) was 9.3% at the recruitment of the study. Baseline BMD at the lumbar spine and proximal femur was similar in both groups, but BTMs were lower in women with DM. Eight women with DM and 13 without DM had fracture at the baseline. Participants received 3 to 6 zoledronate infusions over a median follow-up of 63.5 months. A total of 20 new fractures occurred in 15 participants: 8 (12.7%) women in the DM group and 7 (8.0%) women in the non-DM group. The relative risk (RR) of fractures in DM versus non-DM groups was 1.58 [95% CI, 0.60 to 4.13; P= 0.2]. Conclusion: There is no significant difference in incident fracture outcome between women with and without diabetes with yearly once zoledronate over a follow up of 5 years. So, zoledronate is equally effective in preventing fracture in patients with diabetes as non-diabetes postmenopausal osteoporosis patients. Presentation: Monday, July 14, 2025

Purpose: Zoledronate is most effective when bone turnover is elevated, as in postmenopausal women. In type 2 diabetes mellitus (T2DM), lower bone turnover leads to smaller bone mineral density (BMD) gains compared to non-diabetic (NDM) individuals, and fractures often occur despite preserved BMD. It is unclear whether zoledronate reduces fracture risk in T2DM. No prospective study has directly compared its fracture-preventing efficacy between women with and without T2DM. Aims : To estimate the effect of zoledronate on fracture incidence over 60 months in postmenopausal osteoporotic women with and without T2DM. Methods: This prospective cohort included postmenopausal women with BMD T-scores ≤ –2.5 at either the lumbar spine, femoral neck, or hip. Participants were classified as T2DM or NDM. All received annual zoledronate (4 mg), daily calcium (1000 mg), and cholecalciferol (500 IU), with standardized fall-prevention measures. Fracture history was recorded at follow-up visits, and annual spine radiographs were performed to detect morphometric vertebral fractures. Women completing ≥60 months were included in final analysis. The primary endpoint was fracture incidence; secondary endpoints were changes in BMD and bone turnover markers (BTMs). Results: Of 183 women enrolled, 150 completed 5 years (63 T2DM, 87 NDM; median age 59 years). Baseline BMD was similar, but BTMs were lower in T2DM. During a median 63.5 months, 20 new fractures occurred in 15 women: 8 (12.7%) with T2DM and 7 (8.0%) without. The relative risk was 1.58 (95% confidence interval, 0.60–4.13; P = 0.2). Both groups showed comparable BMD improvements. Conclusion: Annual zoledronate prevented fractures equally in postmenopausal osteoporotic women with and without T2DM over 5 years, indicating similar efficacy despite differences in baseline bone turnover.

AIM:This systematic review and meta-analysis were conducted to assess the glycemic effect of saroglitazar in patients with type 2 diabetes or prediabetes and dyslipidemia. METHODS:PubMed and Google Scholar databases were searched for randomized controlled trials and observational studies till December 2023. The primary outcomes were changes in glycemic parameters such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), and post-prandial blood sugar (PPBS) levels, and the secondary outcomes included changes in lipid profile. The adverse drug reactions were noted and recorded. ROB2 was used for assessing the risk of bias.  Results: A total of 147 studies were screened, and 12 studies were included in the review. There was a significant reduction in FBS (-30.16 (95% CI: -40.36, -19.95) p<0.001, I2=98%), PPBS (-69.09 (95% CI: -85.72, -52.46) p<0.001, I2=96%), and HbA1c (-0.93 (95% CI: -1.18, -0.67) p<0.001, I2=99%) levels following saroglitazar treatment. There was also a significant reduction in total cholesterol of -26.15 (95% CI: -42.44, -9.86) p=0.002, I2=98% and -58.25 (95% CI: -72.21, -44.30) p<0.001, I2=94% in the randomized controlled trials and observational studies, respectively. The study found a significant reduction in low-density lipoprotein and very-low-density lipoprotein levels, along with an improvement in high-density lipoprotein levels, in the saroglitazar group. CONCLUSION:Our meta-analysis has found that saroglitazar causes a significant reduction in the HbA1c, FBS, and PPBS levels in patients treated for diabetic dyslipidemia.

ABSTRACT Background: Myxedematous cretinism, a severe and now rare phenotype of congenital hypothyroidism, has become uncommon due to neonatal screening and iodine supplementation. However, myxedematous cretinism may still be encountered in untreated individuals. Summary: We report two rare adult cases of long-standing untreated congenital hypothyroidism, presenting with mixed features of myxedematous and neurological cretinism, including developmental delay, short stature, hypertonia, and hyperreflexia. Imaging revealed ectopic thyroid in one or thyroid agenesis in another. Conclusion: These cases highlight the rare clinical overlap between neurological and myxedematous cretinism. These also underscore the importance of early recognition to avoid unnecessary workup related to neurological abnormality.

OBJECTIVE:The concept of early gestational diabetes mellitus (EGDM) diagnosed in early pregnancy is rapidly evolving, but there is a need for more data. We sought to compare the pregnancy outcomes between EGDM and late gestational diabetes mellitus (LGDM) in South Indians. METHODS:This retrospective observational study was carried out in the Department of Obstetrics and Gynecology of a tertiary care institute at Puducherry in South India. The study included a total of 2401 singleton pregnant women aged more than 18 years with gestational diabetes (GDM) diagnosed using International Association of the Diabetes and Pregnancy Study Group criteria. The study participants were divided into EGDM and LGDM groups depending on whether GDM was diagnosed before or at or after 24 weeks of gestation. RESULTS:Early gestational diabetes mellitus was observed in 482 and LGDM in 1919 women. EGDM women had a significantly higher mean maternal age (28.5 vs. 27.5 years, P < 0.001), body mass index ≥25 kg/m2 (68.4% vs. 62%, P < 0.001), fewer education years (11.9 vs. 12.2, P = 0.015), and a lower spontaneous conception rate (93.2% vs. 96.7%, P < 0.001). Need for combined insulin and metformin therapy (12% vs. 3.2%, adjusted relative risk (aRR): 2.19, 95% confidence interval [CI]: 1.57-3.05, P < 0.001), metformin alone therapy (35.9% vs. 18.5%, aRR: 1.85, 95% CI: 1.58-2.16, P < 0.001), preterm birth (13.9% vs. 6.5%, aRR: 2.25, 95%CI: 1.69-3.01, P < 0.001), and low birth weight babies (24.5% vs. 17.6%, aRR:1.35, 95%CI: 1.11-1.64, P = 0.002) were significantly higher in women with EGDM relative to LGDM. CONCLUSION:Women with EGDM have significantly worse metabolic profile, greater need for pharmacotherapy, and worse fetal outcomes compared to LGDM.

Diabetes mellitus (DM) is a metabolic disorder that leads to the destruction of various tissues including bones. The pathogenesis of osteoporosis (OP) varies in DM due to many specific factors. DM increases the risk of fracture as well as post-fracture mortality. It is because of this fact that OP treatment should not be neglected in patients with DM. OP therapy comprises anabolic as well as anti-resorptive agents. Primary OP as observed in post-menopausal women is associated with high bone turnover, whereas OP in DM is a disease of low bone turnover. Therefore, anabolic agents seem to be quite promising in cases of OP in DM. Although the anti-fracture efficacy of these drugs is proven beyond any doubt in the general population without DM, evidence in persons with DM is limited. Among the anabolic agents, teriparatide has the most evidence in favor of its efficacy and safety in persons with DM. Studies evaluating other anabolic agents such as abaloparatide and romosozumab in diabetic osteopathy are scarce in the literature. Future studies specifically in both type 1 and type 2 DM populations are needed to evaluate the effects of osteoanabolic agents.

Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) have a strong bidirectional relationship. T2DM increases the risk of developing HCC, mainly through the nonalcoholic steatohepatitis pathway, but a significant proportion of patients develop HCC without developing cirrhosis. The identification of HCC in T2DM patients is difficult considering the low incidence of HCC and the high prevalence of T2DM. However, considering the alarming increase in the incidence of diabetes mellitus in the global population, effective strategies are urgently needed to identify patients at high risk. Nonetheless, various classes of drugs, such as sodium-glucose cotransporter-2 inhibitors and incretin analogs, may be promising for reducing the risk of nonalcoholic steatohepatitis and HCC development in T2DM patients in the future. In this review, we discuss all these facets of the relationship between HCC and T2DM, and we summarize future directions.

INTRODUCTION:Hypothyroidism, a common endocrine disorder, is linked to cardiovascular risks arising from autonomic imbalance and metabolic dysregulation. While overt hypothyroidism (OH) manifests distinct thyroid hormone abnormalities, subclinical hypothyroidism (SCH) presents milder hormonal changes. Levothyroxine therapy is widely used for thyroid function restoration, but its long-term effects on autonomic and cardiovascular health in OH remain understudied. This study investigates the therapeutic effects of six months of levothyroxine treatment on autonomic function and metabolic parameters in OH patients. MATERIALS AND METHODS:A follow-up study was conducted on OH patients receiving levothyroxine therapy. Participants with confounding cardiovascular comorbidities were excluded. Clinical assessments included autonomic function tests, metabolic profiling (lipid and thyroid parameters), and inflammatory/oxidative stress markers. Comparative analyses were performed against healthy controls. RESULTS:Levothyroxine therapy effectively restored thyroid hormone levels in OH patients. Autonomic function tests demonstrated improved parasympathetic modulation and partial sympathovagal balance recovery, though residual autonomic irregularities persisted. Lipid profiles showed marked improvement but did not fully normalize compared to controls. Inflammatory and oxidative stress markers decreased significantly post-therapy, yet remained elevated relative to healthy individuals. Statistical modeling identified oxidative stress as a key contributor to autonomic dysfunction. DISCUSSION:While levothyroxine normalized thyroid function and improved autonomic balance, incomplete resolution of metabolic and inflammatory abnormalities suggests persistent cardiovascular risks in OH patients after six months of therapy. The findings highlight the need for extended treatment durations to achieve comprehensive cardiovascular risk mitigation. CONCLUSION:Despite therapeutic benefits, OH patients retain residual cardiovascular risks post-levothyroxine therapy, necessitating long-term monitoring. Future research should investigate optimal treatment durations and adjunct therapies to address persistent autonomic and metabolic dysfunction in this population.

Introduction:Early gestational diabetes mellitus (EGDM) is a relatively new entity, and there is a lack of clarity regarding treatment. This study was carried out to compare the maternal and neonatal outcomes between treated EGDM and late GDM. Methods:This prospective cohort study was conducted in a tertiary care teaching hospital in South India. Pregnant women more than 18 years of age with a singleton foetus and diagnosed with GDM on a 75 g oral glucose tolerance test (OGTT) using the World Health Organization (WHO) 2013 criteria were included in the study. The study participants were divided into two groups of 306 each, based on their gestational age at the time of GDM diagnosis. EGDM was diagnosed before 24 weeks of gestation, and late gestational diabetes mellitus (LGDM) was diagnosed at or after 24 weeks of gestation. They were followed until delivery, and the pregnancy outcomes, maternal, and perinatal were documented using a predesigned proforma. Results:Among the 612 participants, a significantly higher proportion of elderly gravida (>35 years) was observed in the EGDM group compared to LGDM (9.5% vs. 4.3%, P = 0.01). The need for insulin (13.1% vs. 6.9%; adjusted relative risk [aRR]: 1.91, 95% confidence interval [CI]: 1.15-3.14; P = 0.011) was significantly higher in women with EGDM relative to LGDM, after adjusting for confounders. There were no other significant differences in outcomes between women with EGDM and LGDM. Conclusions:Women with treated EGDM are older and have a significantly higher insulin requirement than LGDM.

Introduction The imbalance between pro- and anti-inflammatory mediators was suggested to be a contributory factor to the manifestations of allergic parthenium dermatitis. Inadequate circulating vitamin D and IL-10 levels can significantly influence the course of this allergic dermatitis. Objective The objective was to study the association between circulating IL-10 levels and vitamin D status in patients with parthenium dermatitis. Materials and methods Patients attending the dermatitis clinic were screened for eligibility, and 88 individuals were recruited. A total of 101 unrelated healthy volunteers were included as controls. Circulating IL-10 cytokine and vitamin D levels were determined in both groups and compared. Results A higher prevalence of vitamin D deficiency (79.5% vs. 59.4%, P = 0.000315) and lower IL-10 levels (6.84 vs. 9.04 pg/ml, P < 0.0001) were observed in the patient group compared to healthy controls. The vitamin D-deficient patients were also found to have significantly lower IL-10 levels. A significant positive correlation between vitamin D and IL-10 levels was observed among individuals with allergic dermatitis. Lower vitamin D and IL-10 levels were associated with higher Dermatology Life Quality Index (DLQI) scores. Conclusion Lower circulating vitamin D and IL-10 levels, observed in patients with parthenium dermatitis, significantly impacted their quality of life. Assessing plasma IL-10 levels could be a potential biomarker for evaluating disease severity and treatment efficacy. Correcting vitamin D deficiency may improve IL-10 levels and enhance treatment outcomes.