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.
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.
Introduction: Hyperinsulinemic hypoglycaemia (HH) is characterised by unregulated insulin secretion, leading to persistent non-ketotic hypoglycaemia with a lack of alternate fuel that induces a severe risk for brain damage and neurodevelopmental abnormalities. Octreotide, a somatostatin analogue, has been effectively administered as subcutaneous injections or depot preparations in diazoxide-unresponsive HH.
Methods: Children and infants with HH receiving short-acting octreotide injections were included. Anthropometric values, hypoglycaemic episodes, HbA1C, and side effects were noted from the records and were followed up for 12 months. Informed written consent was obtained from the parents before administration of a single dose of LAR (long-acting octreotide). Based on home-based glucose monitoring (HBGM), the dosage of LAR was modified, and short-acting octreotide was eventually withdrawn. The patients shared the injection's cost for cost-effectiveness. HH affects the quality of life (QoL) if not diagnosed and controlled adequately. A QoL questionnaire was given before starting LAR and after 6 months of receiving LAR, and the changes were noted accordingly.
Results: Twenty-two patients were diagnosed with HH, of which 11 infants and children were included in the study. Mutations were identified in 7 (63.63%) children. Daily octreotide could be tapered and stopped with the addition of sirolimus in one patient with an increasing dose of LAR to maintain euglycaemia. The hypoglycaemic episodes decreased with increasing dose of LAR with a decrease in the severity. Eight (72.7%) patients showed an improved lifestyle on LAR quantified through a QoL questionnaire.
Conclusion: LAR was found effective in reducing hypoglycaemic episodes with no adverse effects. The patient's parent's satisfaction was higher. Given its high cost, this trial achieved cost-effectiveness by sharing a single sitting of LAR injection.
Introduction: Obesity, dyslipidaemia and insulin resistance are associated with hypopituitarism. The association between these conditions and Sheehan's syndrome (SS) caused by post-partum pituitary gland necrosis is poorly understood. This study aimed to assess cardiovascular risk surrogate markers in SS patients, and we compared clinical, biochemical and radiological testing with healthy controls.
Methods: In this cross-sectional study, we studied 45 patients with SS on standard replacement therapy and compared them with healthy controls. All subjects underwent anthropometric, inflammatory marker and hormonal measurement (adrenocorticotropic hormone (ACTH), stimulated cortisol, insulin-like growth factor-1 (IGF-1), thyroxine (T4), follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), prolactin (Prl), insulin, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP)). Carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) and echocardiography were also performed.
Results: The mean age and body mass index (BMI) of SS patients were 48.1 ± 10.0 years and 24.3 ± 4.3 kg/m2, respectively, while those of controls were 44.6 ± 12.0 years and 24.6 ± 3.2 kg/m2, respectively. Systolic blood pressure was significantly higher in SS (124.6 ± 20.8 vs. 117.0 ± 18.6 mm of Hg, P < 0.05). All SS patients were hypothyroid, and all except one were hypocortisolaemic. Triglyceride (TG) levels were significantly higher in SS patients (165.6 ± 83.3 vs. 117.2 ± 56.1, P < 0.01), but no difference in the prevalence of metabolic syndrome (MetS) was found. hs-CRP (9.1 (5.2-18.5) vs. 1.5 (0.6-2.8), P < 0.001) and IL-6 (4.9 (3.7-7.3) vs. 3.1 (2.0-4.2), P < 0.001) were significantly higher in SS patients. CIMT was significantly increased in SS patients, but no difference in FMD was found. Echocardiography revealed no significant difference in left ventricular (LV) dimensions, interventricular thickness, posterior wall thickness, ejection fraction, LV mass and diastolic function.
Conclusion: SS patients show increased cardiovascular risk with hypertension, dyslipidaemia and increased atherosclerotic and inflammatory markers.
No meta-analysis has holistically analysed and summarized the efficacy and safety of osilodrostat, a novel dual 11β-hydroxylase (cytochrome P450 family 11 subfamily B member 1 [CYP11B1]) and 18-hydroxylase (aldosterone synthase, CYP11B2) inhibitor in managing Cushing's syndrome (CS). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for randomized controlled trials (RCTs) involving patients with CS receiving osilodrostat in the intervention arm. The primary outcome was to evaluate changes in urine free cortisol (UFC) levels. Secondary outcomes were to evaluate alterations in cortisol levels, androgen levels, mineralocorticoid levels, and adverse events. From initially screened 109 articles, data from 2 RCTs involving 144 patients was analysed. After 8-12 weeks of therapy, the odds of achieving a normal 24-hour UFC was higher in patients receiving oslidrostat as compared to placebo. [odds ratio (OR) 21.94 (95% CI: 8.53-56.43); P < 0.00001; I2 = 0%]. The occurrence of adverse events [OR 1.35 (95% CI: 0.52-3.53); P = 0.54; I2 = 0%; low heterogeneity (LH); High certainty of evidence (HCE)], serious adverse events (SAEs) [OR 1.32 (95% CI: 0.30-5.79); P = 0.72; I2 = 0%; LH; HCE], adrenal insufficiency [OR 5.38 (95% CI: 0.91-31.78); P = 0.06; I2 = 0%; LH; HCE], headache [OR 0.98 (95% CI: 0.35-2.76); P = 0.97; I2 = 0%; LH; HCE], hyperandrogenism [OR 3.68 (95% CI: 0.59-22.80); P = 0.16; I2 = 0%; LH; HCE] and deaths [OR 0.32 (95% CI: 0.01-8.00); P = 0.48; I2 = 0%; LH; HCE] was comparable among the groups. The occurrence of nausea [OR 4.25 (95% CI: 1.26-14.30); P = 0.02; I2 = 0%; LH] and arthralgia [OR 6.54 (95% CI: 1.64-26.13); P = 0.008; I2 = 0%; LH; HCE] was significantly higher in the osilodrostat group as compared to placebo. Osilodrostat has good efficacy and safety in CS and was well tolerated over 48 weeks of use.
Idiopathic hirsutism (IH) is a common clinical condition with multiple diagnostic and therapeutic uncertainties. There are no clear recommendations for the diagnosis and management of the condition. This practice update was developed to guide the primary care physicians and the specialists in better and more systematic management of IH particularly in the Indian context. Twelve experienced members consisting of eminent endocrinologists, physicians, a dermatologist, a gynaecologist and a psychiatrist were invited by the Integrated Diabetes and Endocrine Academy (IDEA). A literature search was performed using online databases from PubMed, Cochrane Library and Google Scholar. Published articles from peer-reviewed indexed journals, with a preference for meta-analyses and randomized controlled trials, were selected. A meeting took place with all the 12 members individually giving their opinions on predetermined questions of interest. After the initial meeting during IDEACON 2023, two more meetings were held and the practice update was formulated after voting. Practice updates were made on important areas such as the cut-off for modified Ferriman-Gallwey Score for the Indian population, conditions to be excluded before diagnosing IH, when to refer to specialists, investigations in a suspected case of IH and choice of therapies for its management.