Clinical Characteristics of Macroprolactinomas and Response to Medical Therapy.

Introduction: The presentation of macroprolactinomas and response to treatment may vary according to age, sex and tumour characteristics. To analyse clinical phenotype, biochemical and radiological characteristics of macroprolactinomas presenting to a tertiary care centre. A retrospective observational study from January 2018 to December 2022. Methods: Thirty diagnosed cases (18 females, 12 males) of macroprolactinomas were included and followed up for one year. Results: The most common presentation was headache (73%), visual disturbances (50%), galactorrhoea (33.3%) and loss of libido (26.6%) along with menstrual cycle disturbances (94%), and infertility (55%) in females. Duration of symptoms (2.22 ± 2.87 vs 4.61 ± 3.4 years), tumour size (4.8 ± 2.09 vs 2.75 ± 1.24 cm) and prolactin levels (5153.5 ± 4755.3 vs 1803.5 ± 3785.5 ng/ml) were different significantly between males and females. Good response to medical therapy was observed in 84% of the treatment-naive patients. Conclusion: Macroprolactinomas in males present with shorter duration of symptoms, larger size, higher prolactin levels and more resistant tumours, emphasizing the need for early diagnosis and aggressive management. Medical therapy remains the treatment of choice irrespective of gender.

A Comparison of 06:00 AM Versus 09:00 AM Serum Cortisol as a Basal Morning Cortisol in Guwahati, Assam: A Pilot Study.

Introduction: Cortisol secretion is regulated by circadian rhythm, which is influenced by zeitgebers like light. In India, the entire country operates under a single time zone, Indian Standard Time, which may not align with the local sunrise timing across different regions. Aims: This study aimed to compare the basal serum cortisol levels between 06:00 AM and 09:00 AM in Guwahati, Assam, where sunrise occurs earlier compared with the western part of the country. A cross-sectional pilot study was conducted from December 2022 to June 2023 in a tertiary care hospital in Guwahati. Methods: Serum cortisol samples were collected at 06:00 AM and 09:00 AM from 25 healthy adult participants once in winter and again in summer. Descriptive statistics and paired Student's t-tests were used. Results: The mean serum cortisol levels at 06:00 AM in winter, summer and overall were 13.2, 13.4 and 13.3 µg/dL, respectively. At 09:00 AM, the mean serum cortisol levels in winter, summer and overall were 8.2, 7.7 and 8.0 µg/dL, respectively. Significant differences were observed between the 06:00 AM and 09:00 AM cortisol levels in both winter and summer (P <0.001). Conclusion: This study highlights the importance of considering the influence of earlier sunrise on circadian rhythm, cortisol secretion and sampling protocols. Recognising the impact of earlier sunrise on cortisol secretion and adapting sampling protocols accordingly to align with the local sunrise can provide a more accurate assessment of basal cortisol levels and help avoid potential misinterpretation and diagnostic challenges associated with low values.

Pituitary Stalk Interruption Syndrome: Analysis of Response to Growth Hormone Therapy.

OBJECTIVE: To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS). METHODS: A retrospective analysis of confirmed cases of PSIS was performed. The development of new pituitary hormonal deficiencies and response to recombinant human growth hormone (rhGH) therapy were assessed during follow-up. RESULTS: This study included 14 children (10 boys) of PSIS with median (range) age of 12.15 years (2 months - 18 years). Short stature was the most common presentation (n = 13), and micropenis (n = 4), cleft lip (n = 1) and single central incisor (n = 1) were other midline defects. Growth hormone (GH) deficiency was present in 14 children and 7 of them also had multiple pituitary hormone deficiencies at baseline. Central hypothyroidism (n = 5), secondary adrenal deficiency (n = 4) and gonadotropin deficiencies (n = 2) were also seen. All children received rhGH. The mean height gain on follow-up was 12.78 cm in first year (n = 14), 6.5 cm in second year (n = 8) and 4.07 cm in third year (n = 7) of rhGH therapy. Four children developed additional pituitary hormone deficiency on follow-up. CONCLUSION: Short stature with isolated GH deficiency was the most common presentation of PSIS that showed good response to rhGH therapy.

Zoledronic Acid Treatment in Infants and Toddlers with Osteogenesis Imperfecta is Safe and Effective: A Tertiary Care Centre Experience.

Context: Osteogenesis imperfecta (OI) is a genetic disorder of the extracellular matrix of bone characterized by low bone mass manifesting as frequent fractures, delayed motor development, pain, and impaired quality of life. The intravenous bisphosphonate, pamidronate is an established treatment for OI. Recently, zoledronic acid (ZA) has been used for the management of OI. Aim: To assess the efficacy and safety of ZA in children below five years of age with OI. Settings and Design: A hospital-based prospective observational study. Methods and Material: Patients with OI aged less than five years attending our centre were treated with intravenous ZA at a dose of 0.05 mg/kg every six months. Subjects were closely monitored for clinical and biochemical variables, adverse events, and new-onset fractures. The response to therapy was assessed by monitoring clinical variables including the degree of bony pains, number of fractures, height/length standard deviation score (SDS), and motor developmental milestones. All patients were analysed at baseline and at the end of two years for biochemical parameters and clinical severity score (CSS) as proposed by Aglan et al. with modifications. Results: After two years of treatment, OI patients showed a significant decline in the rate of fractures (p < 0.001), improvement in ambulation (p = 0.005), alleviation of pain (p < 0.001), and improvement in height SDS (p < 0.05). There was a significant improvement in CSS after two years of therapy. Apart from mild flu-like symptoms and mild asymptomatic hypocalcaemia immediately post-infusion, no other adverse effect was noted. Conclusion: ZA therapy in infants and children below five years of age with OI was effective and safe and a more convenient alternative to pamidronate.

A Study of Serum Adiponectin Levels in Patients with Polycystic Ovarian Syndrome and its Correlation with Various Cardiometabolic Risk Markers.

Background: Polycystic ovarian syndrome (PCOS) is the most common metabolic disorder in the reproductive age group, the pathogenesis of which is constantly evolving with the discovery of novel molecules and the lookout for potential therapeutic targets. Aims: The aim of the present study was to estimate the circulating levels of serum adiponectin in patients with PCOS compared to controls and to find its correlation with markers of cardiovascular risk, with special emphasis on circulating levels of oxidised low-density lipoprotein (oxLDL). Settings and Design: In this cross-sectional observational study recently diagnosed, PCOS subjects were compared with age- and body mass index (BMI)-matched controls. Materials and Methods: All the included subjects underwent detailed clinical, biochemical and hormonal evaluation, including lipid profile, 75 g oral glucose tolerance test, fasting serum insulin, fasting serum adiponectin, oxLDL, total testosterone and anti-Mullerian hormone. Statistical Analysis Used: Appropriate statistical methods were performed using SPSS (version 21) and Microsoft Excel (2019). Results: A total of 56 PCOS cases and 32 controls were included in the study. Mean values of serum adiponectin (µg/mL) in our study were found to be significantly lower in PCOS cases (11.53 ± 4.74) versus controls (14.73 ± 5.61) irrespective of BMI. Mean values of serum oxLDL (µg/dL) were found to be higher in PCOS cases (157.96 ± 53.89) versus controls (117.52 ± 45.44), with a significant negative correlation between adiponectin and oxLDL in cases. No difference in levels of adiponectin was found between the different PCOS phenotypes. Conclusion: Hypoadiponectinaemia was found to be associated with PCOS irrespective of obesity in PCOS subjects. Serum oxLDL can complement adiponectin as early predictor of CV risk in PCOS.

"Spectrum of 46 XY Disorders of Sex Development": A Hospital-based Cross-sectional Study.

BACKGROUND: Disorders of sex development (DSD) are a wide range of relatively rare conditions having diverse pathophysiology. Identification of an underlying cause can help in treating any coexisting hormone deficiencies and can help with anticipating any other immediate or long-term health concerns. OBJECTIVE: To study the clinical and biochemical profile of patients with 46 XY DSD along with androgen receptor (AR) gene mutation status in selected group of patients. METHODS: A cross-sectional study was conducted after enrolling the eligible DSD patients. Thorough elicitation of history and detailed clinical examination was done. Assays for luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, androstenedione, AMH & Inhibin B (where indicated), and human chorionic gonadotropin stimulation were done as per protocol. RESULTS: In total, 48 patients were included in the study. Ambiguous genitalia (58.3%) followed by hypospadias (33.3%) were common presentation. Androgen biosynthetic defect were the most commonly encountered diagnosis followed by androgen insensitivity syndrome (AIS). Swyer syndrome was diagnosed in 4.2% of cases; partial gonadal dysgenesis, ovotesticular DSD, and vanishing testis syndrome contributed to 2% of cases each. Eight cases (16.7%) who presented with isolated proximal and midshaft hypospadias for whom no diagnosis was found were categorized in the "etiology unclear" group. AR gene mutation analysis designed against specific exons did not yield any results. CONCLUSION: 46 XY DSD is a heterogeneous group of patients with a varying age of presentation and a diverse clinical profile. Most patients are reared as males and maintained the same gender identity except in isolated cases. Diagnosis of AIS remains a clinical challenge as a definite hormonal criterion does not exist and genetic mutations in AR gene may be negative. Flanking region sequencing, whole genome sequencing, and promoter region sequencing may reveal pathogenic variants. Variations in other genes regulating AR pathway may also be candidates to be studied.

A Study of Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus: A Northeast India Experience.

AIM: To investigate the prevalence and the risk factors for cardiac autonomic neuropathy (CAN) in type 2 diabetes mellitus (DM) patients. STUDY DESIGN: Cross-sectional cohort study. PLACE AND DURATION OF STUDY: This study was conducted in the Department of Endocrinology, Gauhati Medical College and Hospital, Assam, India between December 2016 to March 2018. METHODOLOGY: We included 100 patients (60 males and 40 females; age range: 36-72 years) with type 2 DM. Their clinical, biochemical, and metabolic parameters were analyzed and assessment of CAN were done based on the Ewing's criteria. RESULTS: Out of 100 patients, 60 were males and 40 were females. The mean age of the patients was 53.3 ± 10.37 years (36-72 years) and the mean duration of diabetes was 9.03 ± 6.4 years (6 months-25 years). Patients were divided into two groups: "without CAN" (CAN-) and "with CAN" (CAN+). The prevalence of CAN was 70%, with early CAN in 25%, definite CAN in 24%, and severe CAN in 21% cases The patients with CAN were older (P = 0.0005), had longer diabetes duration (11.56 vs. 3.13; P = 0.0001), higher creatinine (P < 0.0001), and lower estimated glomerular filtration rate (eGFR) (P = 0.0001) compared to patients without CAN. Retinopathy, peripheral neuropathy, and nephropathy were common in CAN + patients. On multiple logistic regression analysis, duration of diabetes [odds ratio (OR); 6.7, P < 0.0001), older age (OR; 1.07, P < 0.016), and lower eGFR (OR; 0.97, P < 0.03) were risk factors for CAN. CONCLUSION: CAN is a common microvascular complication in type 2 DM with duration of diabetes, age, and severity of nephropathy being its significant determinants.

Vitamin D Status of School Children in and around Guwahati.

CONTEXT: Peripubertal and adolescent children are vulnerable to vitamin D deficiency as this is the period of rapid skeletal growth. AIMS: This study was done to assess the vitamin D status in school children between the age of 8-14 years attending the government schools in rural and urban areas of Assam in Northeast India. SETTINGS AND DESIGN: This was a cross-sectional observational study. MATERIALS AND METHODS: About 500 students (350 from rural and 150 from urban areas) were recruited in the study. Serum 25-hydroxy vitamin-D [25(OH)D], parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase were measured in fasting state. Daily nutrition intake and sunlight exposure were assessed. STATISTICAL ANALYSIS: Student's t-test and Pearson correlation test were done to assess the association between different variables. P value <0.05 was considered significant. RESULTS: The prevalence of vitamin D deficiency was 8.4% and vitamin D insufficiency was 14.2%. There was no significant difference of mean 25(OH)D levels and sun exposure between rural and urban children. Out of 42 children with vitamin D deficiency, 36 (85.7%) had sun exposure <20% and 41 (97.6%) had calcium intake < 1000 mg/day. The rural children had a higher calcium intake as compared to urban children (P = 0.005). There was a significant positive correlation of mean 25(OH)D levels with serum calcium, sun exposure and calcium intake. CONCLUSION: The prevalence of vitamin D deficiency in peripubertal and adolescent age group children in and around Guwahati city of Assam is comparatively lower than that in other parts of the country.

Pulmonary alveolar proteinosis in a 10-year-old girl masquerading as tuberculosis.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease. Diagnosis is established by bronchoalveolar lavage (BAL), which has macroscopic 'milky appearance', and in the presence of typical computed tomography, findings are diagnostic of PAP but, however, the feature of periodic acid-Schiff-positive eosinophilic proteinaceous fluid raises the confidence of the diagnosis. We report late-onset PAP in a 10-year-old girl who had acid fast bacilli on an initial BAL examination, but was subsequently diagnosed as PAP.