GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

Diagnostic characteristics and management outcome in patients with acromegaly: A 15-year experience at a tertiary care hospital in Pakistan.

OBJECTIVE: To assess the diagnostic features of acromegaly, and analyse its management outcomes over a 15-year period in a tertiary care setting. METHODS: The descriptive, cohort, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of adult patients of either gender diagnosed with acromegaly based on biochemical and radiological evidence between January 2005 and December 2019. Data was retrieved from the medical records. Data was analysed using SPSS 19. RESULTS: Of the 84 subjects, 54(64.3%) were males and 30(35.7%) were female. The overall mean age was 38.69±13.52 years. The patients presented 5.43±4.3 years after the onset of symptoms, with somatic growth features, such as enlarged hands and feet which was the most common complaint 81(96.4%). Of all the patients, 73(86.9%) underwent trans-sphenoidal surgery for the removal of the pituitary adenoma, while 11(13.1%) opted out of the surgical option. Further, 9(12.3%) patients showed biochemical and radiological remission 6 months post-surgery. Out of the remaining 64(87.7%) patients, 38(59.4%) received radiosurgery or radiotherapy, 15(23.4%) underwent repeat trans-sphenoidal surgery, and 11(17.2%) chose medical treatment. CONCLUSIONS: Majority of patients failed to achieve remission after trans-sphenoidal surgery, which is the first line of treatment. Radiotherapy/repeat surgery was generally the options taken by those with persistent disease.

Peripheral arterial disease (PAD) in diabetics: diagnosis and management- a narrative review.

Peripheral arterial disease (PAD) in diabetic patients is often overlooked due to associated neuropathy. The very first presentation of these patients is with an Ischaemic ulcer or toe gangrene. Diabetics have a very high amputation rate compared to non-diabetic patients due to diffuse multi-segmental disease in the calcified tibial arteries. Early detection of the condition is a challenge in these patients. Even ankle-brachial pressure index may not be reliable. Both surgical and endovascular options are effective in wound healing. Endovascular techniques include percutaneous transluminal angioplasty with and without stenting, sub-intimal angioplasty, percutaneous transluminal angioplasty with drug-coated balloons, covered stents, and use of atherectomy devices. The current narrative review was planned to discuss the essentials of diagnosing PAD in diabetic patients and its various treatment options.

Enhancing Diabetes Care in LMICs: Insights from a Multinational Consensus.

The International Cardio-Metabolic Forum held a plenary session to establish a multinational consensus on the challenges faced in diabetes management within lower-middle-income countries (LMICs) and their potential solutions. Stakeholders, including patients, family/caretakers, healthcare professionals, and healthcare policymakers & organizations, participated in discussions. The audience of 280 doctors from 15 different countries (Pakistan, Qatar, Sri Lanka, Kenya, Myanmar, Georgia, Nigeria, Philippines, Uzbekistan, Iraq, Tanzania, Cambodia, Kazakhstan, South Sudan and Libya) was divided into 4 groups led by Group Leaders to represent each stakeholder group. Questionnaires addressing key challenges and solutions specific to each group were used to facilitate consensus development. Participants voted on relevant options based on their clinical experience. SLIDO software was used for polling, generating separate results for each group. The insights shared by healthcare professionals highlighted the importance of improving medication accessibility and cost-effectiveness for patients, emphasizing the need for adherence to treatment plans and lifestyle modifications. The significance of balanced nutrition with low glycemic index food for enhancing quality of life was recognized. Caregivers of diabetic patients with comorbidities face increasing demands for care, particularly in relation to age-related milestones. Healthcare professionals emphasized the challenges posed by cultural beliefs and health awareness, underscoring the importance of teamwork and early referral for managing comorbidities. Healthcare policymakers need to focus on disease education, awareness programs, screening guidelines, and advocacy for community and clinical screening. By addressing these challenges, a more comprehensive and effective approach to diabetes management can be achieved in LMICs, ultimately improving outcomes for individuals with diabetes.

Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)-3 in the diabetic host.

Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We investigated mycobacterial antigen-stimulated responses in peripheral blood mononuclear cell (PBMC) isolated from healthy endemic controls (EC), those with LTBi, DM groups with and without LTBi, as compared with TB patients. Cytokines were measured using a Luminex-based assay. Gene expression was determined by RT-PCR. In DM-LTBi cases, PPD-stimulated proinflammatory cytokines; IFN-γ, IL-6, IL-2, TNF-α and GM-CSF and anti-inflammatory cytokines, IL-5 and IL-13 were raised as compared with EC. DM-LTBi PPD-stimulated IFN-γ, IL-6 and TNF-α mRNA titres were found raised in DM-LTBi, whilst suppressor of cytokine signalling (SOCS)-3 expression was lowered. Within DM cases, stratification based on HbA1c levels revealed raised IFN-γ but lowered IL-6 gene expression in those with controlled levels as compared with uncontrolled glycaemic levels. Further, SOCS1 expression levels were found higher in DM cases with controlled glycaemia when compared with EC. Overall, we show that diabetics with LTBi manifest raised levels of inflammatory and anti-inflammatory cytokines concomitant with reduced SOCS3 mRNA expression. Reduced glycaemic control results in further inflammatory dysregulation impacting conversing impacting IFN-γ and IL-6 activation. These results suggest that dysregulated immune activation in diabetes is exacerbated by LTBi, lack of glycaemic control may further compromise immunity against MTB infection.

Functional pituitary gonadotroph adenoma in male patients: Case report.

Pituitary gonadotroph adenomas are common but very rarely do they secrete biologically active luteinizing hormone (LH) and follicle-stimulating hormone (FSH). There have been case studies reporting high sex hormones (testosterone/estrogen) in the presence of high or normal LH and FSH. Here we report two cases (with their consent) who presented with visual disturbance and headache at a tertiary care hospital (Aga Khan university hospital) Karachi, Pakistan. Brain imaging revealed a pituitary macroadenoma. Further workup was consistent with pituitary gonadotroph adenoma with high FSH (case 1) and normal LH/FSH (case 2) and elevated serum testosterone in both cases. Transsphenoidal resection was performed and the tissue sample histopathology confirmed pituitary adenoma. Postoperatively, improvement in hormonal profile was observed along with a resolution of visual disturbances and headaches. Thus, functional gonadotroph adenoma should be considered in the presence of elevated testosterone/estrogen and normal or elevated follicle-stimulating hormone (FSH)/ luteinizing hormone (LH). Early diagnosis leads to a better outcome.

Clinical and biochemical outcomes of Sodium-Glucose CoTransporter-2 (SGLT2) Inhibitors in Type-2 Diabetes Mellitus Patients as a fourth oral anti diabetic medicine.

Objectives: To evaluate the clinical and biochemical effects of (SGLT2) inhibitors as a fourth oral anti-diabetic drug in patients with Type-2 diabetes mellitus (T2DM). Methods: In a tertiary hospital in Karachi, Pakistan, a retrospective assessment of patient medical records was conducted from January 1, 2017 to December 31, 2020.A total of one hundred patients (mean age [Standard Deviation]: 53.8 [9.63] years) with poorly controlled T2DM were included. Data was collected before the SGLT-2 inhibitor was added, as well as three and six months after the medicine was started. Weight, BMI, blood pressure (BP), HbA1c, SGPT, and Creatinine were measured at the start and during the study. Results: There was a significant reduction in HbA1c (p-value < 0.001) with a mean reduction (MR) of 0.81+1.02% at three months and 1.07+1.11% at six months. A mean weight reduction (p-value < 0.001) of 1.83+2.32 kg at three months and 4.02+6.04 kg at 6 months, respectively, was recorded. A mean BMI reduction of 0.69+0.95 kgm-2 at three months and 2.13+3.41 kgm-2 at six months of follow up, respectively were recorded. A systolic blood pressure (SBP) also showed a significant reduction (p-value < 0.05) with a MR of 5.9+15.76 mmHg at three months and 6.37+18.33 mmHg at 6 months, respectively. Non-significant variation in creatinine and SGPT was also noted. Conclusions: SGLT-2 is an effective oral anti-diabetic medicine that can help individuals with diabetes who are currently using glucose-lowering oral anti-diabetic medications. These medications can help diabetic patients stick to their regimen.

Prevalence of Comorbidities among Patients with Acromegaly.

BACKGROUND AND OBJECTIVE: Acromegaly is a chronic disorder resulting from excessive secretion of growth hormone and (GH) and insulin-like growth factor 1 (IGF-1) and is associated with several comorbidities. These complications contribute significantly to morbidity and mortality associated with this condition thus early diagnosis leads to better outcomes. There have been studies in other countries to assess the comorbidities associated with acromegaly. However, we do not have any recent data with regards to Pakistan. So, in order to demonstrate the prevalence of demographics, hormonal disorders, and other complications associated with acromegaly we conducted this study. METHODS: It is a retrospective review of patients' records presented to the tertiary care Hospital, Karachi, Pakistan for the diagnosis and management of acromegaly and the complications associated with this condition between the time periods 2000 till 2020. A total of 89 patients fulfilled the inclusion criteria of acromegaly and were included in the study. Comorbid conditions were described based on current guidelines. Patient baseline characteristics were recorded along with other complications arising during treatment. RESULTS: Eighty-nine patients were included. 64% were male, over 70% were older than 30 years old and more than 40% of patients had BMI greater than 30. HTN, pre-hypertension, and CCF were reported in 35.95%, 3.37%, and 6.74%. Diabetes mellitus, hypocortisolism, hypothyroidism, hypogonadism, and hyperprolactinemia were reported in 39.32%, 38.20%, 37.07%, 34.46%, and 16.85% of cases. The prevalence of osteoarthritis, blood disorder, skin changes, thyroid cancer, and spinal stenosis was found out to be around 1.12% each. CONCLUSIONS: Acromegaly is associated with cardiovascular and endocrinal disorders. Screening for these disorders at the time of diagnosis can lead to early management and better outcomes translating into decreased mortality.

Tumour induced osteomalacia.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually presenting with bone pain, fracture of bones and muscle weakness. It is caused by high serum levels of fibroblast growth factor 23 (FGF- 23), which is a hormone-regulating phosphate, and vitamin D. FGF-23 is secreted by several tumours, especially benign mesenchymal tumours which are very small and difficult to locate. There is a significant delay from onset of symptoms to the diagnosis of this entity dueto occult nature of this disease. We present a case of young male who presented with long history of progressively worsening muscular pain and weakness, rendering the patient confined to bed. Our aim of presenting this patient as a case report is to make physicians realise that any patient with unexplained muscular weakness and pain must undergo workup for TIO, including serum phosphate measurement, as this is a rare but potentially curable disease.

Diagnostic validity of ultrasonography in thyroid nodules.

OBJECTIVE: To determine the diagnostic validity of thyroid ultrasound in differentiating between benign and malignant thyroid nodules. METHODS: The cross-sectional study was conducted at Aga Khan University Hospital, Karachi, from August 2011 to January 2013, and comprised all patients of either gender with thyroid nodules referred for ultrasound thyroid and fine needle aspiration cytology. Ultrasonography was performed by radiologists and ultrasound parameters were assessed and compared with cytology results in all nodules. Diagnostic validity of each ultrasound feature was calculated. RESULTS: Of the 101 patients, 81(80%) were female. The overall mean age was 43±13 years (range: 15-73 years). On histocytopathology, 96(95%) nodules were benign and 5(4.9%) were malignant. The sensitivity and specificity of ultrasound features in predicting malignancy were calcification 80% and 68%; hypoechogenecity 80% and 52%; ill-defined lobulated margin 40% and 96%; solid 80% and 40%; taller than wider 50% and 63%. Each ultrasound feature had negative predictive value ranging from 95% to 98% in malignant nodules. CONCLUSIONS: Identification of calcification, hypoechogenecity and solid with ill-defined margins in a thyroid nodule on ultrasound was helpful in suspecting thyroid malignancy and warranted urgent diagnostic fine needle aspiration cytology.

Importance of measuring non-HDL cholesterol in type 2 diabetes patients.

OBJECTIVE: To study the correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol in patients with Type 2 diabetes mellitus and the proportion of patients achieving Adult Treatment Panel III recommended goals. METHODS: The cross sectional study was conducted at the Diabetic Clinic, Aga Khan University Hospital, Karachi. Data of Type 2 diabetes mellitus patients who attended the clinic bewteen 2007 and 2011 was reviewed. All Type 2 diabetic patients of either gender with fasting lipid profile irrespective of taking lipid lowering therapy were included.Type-1 DM, gestational diabetes, type 2 diabetes patients with pregnancy and those with incomplete data were excluded. Correlation between the low-density lipoprotein and Non-high-density lipoprotein was assessed by applying Cramer V and phi. Proportion of patients achieving Adult Treatment Panel III recommended goals was checked. Multivariable regression was done to identify common factors associated with elevated Non-high-density lipoprotein cholesterol. RESULTS: A total of 1352 patients fulfilling the eligibility criteria were included in the study. Mean age of the patients was 54.5 +/- 11.3 years; 797 (59%) were males; 1122 (83%) had Body Mass Index above 25; and 1016 (75%) had HbA1c > or = 7%. Mean Non-high-density lipoprotein cholesterol was 129 +/- 42 mg/dl. Mean low-density lipoprotein cholesterol was 100 +/- 37 mg/dl. Both low-density lipoprotein < or = 100 and Non-HDL < or = 130 mg/dl was achieved in 645 (48%) patients. It is important to note that although 728 (53.8%) patients achieved target LDL cholesterol of < or = 100 mg/dl, among them 83 (11.4%) had Non-high-density lipoprotein cholesterol still above the target > 130 mg/dl (p < 0.05). Out of 752 patients with Non-high-density lipoprotein cholesterol < or = 130 mg/dl, 645 (86%) had low-density lipoprotein cholesterol below 100 mg/dl. Cramer V and Phi showed that correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol was 0.71 (p value < 0.01). After adjusting for other covariates, low-density lipoprotein cholesterol > 100 mg/dl was independently associated with having Non-high-density lipoprotein cholesterol > 130 mg/dl (Adjusted Odds Ratio 38.6; 95% Confidance Interval = 28.1-53.1). Similarly, age < or = 60 years was 60% more likely to have Non-high-density lipoprotein cholesterol > 130 mg/dl (Adjusted Odds Ratio 1.6; 95% Confidance Interval = 1.01 - 2.3). Whereas having obesity Body Mass Index > 25 was 3.6 times more associated to have Non-high-density lipoprotein > 130 mg/dl (Adjusted Odds Ratio 3.6; 95% Confidance Interval = 1.6-7.7). In patients with coronary artery disease, combined goal achievement of low-density lipoprotein < or = 70 mg/dl and Non-high-density lipoprotein cholesterol < or = 100 mg/dl was seen in 59 (35%). Among patients with high-density lipoprotein < or = 70 mg/dl, 8 (10%) had Non-high-density lipoprotein > 100 mg/dl (p < 0.05). CONCLUSION: The study showed a correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol. As measuring Non-high-density lipoprotein cholesterol in Type 2 DM patients is simple, cost-effective and convenient because it does not require 12-hour fasting which may be a risk for hypoglycaemia in these patients, clinicians may choose Non-high-density lipoprotein as a routine measure in everyday practice.

Paroxysmal atrial fibrillation and hemochromatosis: a narrative review.

Paroxysmal atrial fibrillation (PAF) and hemochromatosis have a complex relationship. This review explores its mechanisms, prevalence, correlations, and clinical manifestations. Hereditary hemochromatosis (HH) involves iron overload due to HFE protein mutations, while atrial fibrillation (AF) is characterized by irregular heart rhythms. Iron overload in hemochromatosis can promote cardiac arrhythmias. AF is prevalent in developed countries and may be linked to cryptogenic strokes. Genetic variations and demographic factors influence the occurrence of both conditions. HH affects multiple organ systems, including the heart, while AF causes palpitations and reduced exercise tolerance. Diagnosis involves iron markers, genotypic testing, and electrocardiogram (ECG) findings. Treatment strategies focus on reducing iron levels in hemochromatosis and managing AF through antithrombotic therapy and rhythm control. Untreated hemochromatosis carries a higher risk of complications, and PAF is associated with increased cardiovascular-related mortality. For better understanding of the mechanisms and to improve management, additional studies are required. Tailored approaches and combined treatments may enhance patient outcomes.

Clinical and Biochemical Characteristics of Male Idiopathic Hypogonadotropic Hypogonadism Patients: A Retrospective Cross Sectional Study.

BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) is a medical condition where there is a deficiency or insensitivity of gonadotropin-releasing hormone (GnRH) without a known cause. Not only are the sexual characteristics of a person affected by this condition but also are the psychological and physical development, thus necessitating its early recognition and treatment. This research was carried out to identify the laboratory parameters and to present symptoms of the patients with complaints of IHH. MATERIALS AND METHODS: This retrospective, center, single-center, cross-sectional study was carried out in Aga Khan University from December 2000 until December 2020 on the patients that presented to the clinic with IHH. The patients included in the study were those that presented with hypogonadism, a low concentration of sex steroid hormone, and an abnormal gonadotropin level without any expansive pituitary or hypothalamic lesion. RESULTS: Seventy nine patients presenting with IHH were included with their mean age of 24.2 ± 7.5 years. Of these, 64 (81.0%) had genital atrophy, 50 (63.6%) showed an absence of secondary sexual characteristics, 53 (67.1%) complained of infertility, 44 (55.7%) had not shown signs of puberty, 52 (65.8%) had erectile dysfunction, 46 (58.2%) had a decrease in libido, 11(13.9%) had a previous familial history, 24 (30.3%) had gynecomastia, 9 (11.4%) had non-descended testes, and 6 (7.6%) had anosmia. These patients had serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels of 26.3 ± 60, 1.3 ± 2.4, and 2.7 ± 5.0 (IU/L), respectively. CONCLUSION: Thus, it can be stated that small genitalia is the most common complaint among patients with IHH, followed by infertility and lack of secondary sexual characteristics. The testosterone level in serum is also found to be low among these patients.

Vitamin D and polycystic ovary syndrome (PCOS): a review.

A common health problem known as polycystic ovarian syndrome (PCOS), is characterized by irregular periods, an excess of androgen production, and polycystic ovaries. It is one of the most prevalent endocrine disorders in women of reproductive age, affecting 4-20% of women worldwide. Numerous studies have found a connection between the onset and symptoms of PCOS and Vitamin D insufficiency. Vitamin D insufficiency causes calcium dysregulation and follicular arrest in women with PCOS, which is connected to menstrual irregularities and fertility issues. Studies have connected PCOS metabolic alterations to VDR polymorphisms such as iApa-I, Taq-I, Cdx2, and Fok-I. Insulin resistance is directly related to Vitamin D, is one of the most distinctive characteristics of the PCOS phenotype. Thus, it is suggested that Vitamin D therapy may help PCOS patients with their insulin sensitivity. In addition to insulin resistance, cardiovascular issues are a second metabolic disturbance that PCOS patients with low Vitamin D levels experience. Dyslipidemia is not linked to an increased risk of cardiovascular disease in PCOS-affected women. Vitamin D dramatically improves glucose metabolism by increasing insulin production, insulin receptor expression and reducing pro-inflammatory cytokines. The effect of Vitamin D on the metabolic and reproductive dysfunctions associated with PCOS may be mediated by an overall impact on insulin resistance. Vitamin D supplementation improved menstrual periods, increased folliculogenesis, and decreased blood testosterone levels in PCOS patients, all of which had a significant impact on the ability to procreate. As a result, it might be a cutting-edge therapeutic strategy for treating PCOS concurrently.

A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis.

BACKGROUND: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency in the presence of normal plasma renin and aldosterone level. Focal segmental glomerulosclerosis (FSGS) is a form of glomerular disease associated with proteinuria and nephritic syndrome. This is the first case of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. CASE PRESENTATION: An eight month old boy presented with increased genital pigmentation. Initial investigation revealed that he was glucocorticoid deficient and was started on hydrocortisone and fludrocortisone with a diagnosis of primary adrenal insufficiency. Later fludrocortisone was withdrawn and he was diagnosed to have isolated glucocorticoid deficiency. He later developed focal segmental glomerulosclerosis for which he underwent renal transplantation at the age of five years. Now at the age of twelve years, this boy is doing well on hydrocortisone treatment. His two siblings and a first degree cousin also had isolated glucocorticoid deficiency. One of the above two siblings died due to renal failure secondary to focal segmental glomerulosclerosis. CONCLUSION: Patients with familial glucocorticoid deficiency should be carefully followed for development of features of nephrotic syndrome.

Male hypogonadism at a tertiary care hospital in Karachi, Pakistan.

BACKGROUND: Male hypogonadism is defined as 'inadequate gonadal function, manifested by deficiency in gametogenesis and/or secretion of gonadal hormones'. Signs and symptoms of hypogonadism depend primarily on the age of onset. It can be classified according to the site primarily involved: the gonads, the hypothalamus, or the pituitary gland. The objective this study was to determine the presentation and aetiology of male hypogonadism seen in a tertiary care hospital. METHODS: This cross-sectional study was conducted at Endocrine Clinics, Aga Khan University Hospital Karachi. Data of male patients with hypogonadism who attended clinics during January 2009 to August 2011 were reviewed. All male patients with clinical and biochemical evidence of hypogonadism were included in the study. Patients with Diabetes Mellitus, Metabolic Syndrome, Andropause, AIDS, Chronic Renal Failure, and Cirrhosis were excluded. Mean +/- SD were computed for quantitative variables. Frequency and percentages were computed for qualitative variables. Aetiology of male hypogonadism was categorised as primary and secondary hypogonadism. RESULTS: A total of 85 patients with male hypogonadism attended the endocrine clinic. Mean age of patients was 25 +/- 10 years. Clinical presentations were small genitalia (65%), absent secondary sexual characteristics (53%), not attained puberty (47%), infertility (53%), erectile dysfunction (41%) and loss of libido (29%). Seventy-three (86%) patients had hypogonadotrophic hypogonadism (secondary hypogonadism) and 12 (14%) patients had hypergonadotrophic hypogonadism (primary hypogonadism). Among the patients with hypogonadotrophic hypogonadism 38 had idiopathic hypogonadotrophic hypogonadsim, 7 had pituitary adenoma, 6 had empty sella syndrome, 3 had Kallman's syndrome, and 1 patient had haemosiderosis due to thalassaemia major; 18 patients did not undergo brain imaging. CONCLUSION: Small genitalia, absent secondary sexual characteristics and infertility were the main presenting features of hypogonad men. Majority of patients had hypogonadotrophic hypogonadsim.

Diabetic Myonecrosis: A Vascular Complication.

Diabetic myonecrosis is an unpublicised problem that can occur in patients having either type 1 or type 2 diabetes mellitus. It usually affects patients who have long-standing, uncontrolled diabetes with associated microvascular complications. We report a case of a 78-year female with diabetic myonecroses admitted to a tertiary care hospital. Although it is a self-limiting disease, we lay down the management approach of how to exclude the extensive list of differential diagnoses and limit the life-threatening complications as urgent evaluation is critical. Clinicians taking care of patients with uncontrolled diabetes should be mindful and aware of the complication of diabetic myonecrosis in a patient presenting with pain in any limb and having negative venous doppler ultrasound for deep vein thrombosis. Magnetic resonance imaging (MRI) is the most specific and sensitive modality for diagnosis. Muscle biopsy can be used for anomalous cases. Although diabetic muscle infarction is a rare pathology, it presents a high risk for diabetes-related morbidity and mortality. Key Words: Myonecrosis, Diabetes mellitus, Doppler ultrasound, Magnetic resonance imaging.

Rapid adsorption of selenium removal using iron manganese-based micro adsorbent.

Selenium in wastewater is of particular concern due to its increasing concentration, high mobility in water, and toxicity to organisms; therefore, this study was carried out to determine the removal efficiency of selenium using iron and manganese-based bimetallic micro-composite adsorbents. The bimetallic micro-composite adsorbent was synthesized by using the chemical reduction method. Micro-particles were characterized by using energy-dispersive X-ray spectroscopy for elemental analysis after adsorption, which confirms the adsorption of selenium on the surface of the micro-composite adsorbent, scanning electron microscopy, which shows particles are circular in shape and irregular in size, Brunauer-Emmett-Teller which results from the total surface area of particles were 59.345m2/g, Zeta particle size, which results from average particles size were 39.8 nm. Then it was applied to remove selenium ions in an aqueous system. The data revealed that the optimum conditions for the highest removal (95.6%) of selenium were observed at pH 8.5, adsorbent dosage of 25 mg, and contact time of 60 min, respectively, with the initial concentration of 1 ppm. The Langmuir and Freundlich isotherm models match the experimental data very well. The results proved that bimetallic micro-composite could be used as an effective selenium adsorbent due to the high adsorption capacity and the short adsorption time needed to achieve equilibrium. Regarding the reusability of bimetallic absorbent, the adsorption and desorption percentages decreased from 50 to 45% and from 56 to 53%, respectively, from the 1st to the 3rd cycle.

A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review.

Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype-phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype-phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency. To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up.

Adolopment of adult diabetes mellitus management guidelines for a Pakistani context: Methodology and challenges.

Introduction: Pakistan has the highest national prevalence of type 2 diabetes mellitus (T2DM) in the world. Most high-quality T2DM clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local T2DM CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of adult DM in Pakistan. Methods: We employed the GRADE-ADOLOPMENT approach utilizing the T2DM CPG of the American Diabetes Association (ADA) Standards of Medical Care in Diabetes - 2021 as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. Results: The source document contained 243 recommendations, 219 of which were adopted without change, 5 with minor changes, and 18 of which were excluded in the newly created Pakistani guidelines. One recommendation was adapted: the recommended age to begin screening all individuals for T2DM/pre-diabetes was lowered from 45 to 30 years, due to the higher prevalence of T2DM in younger Pakistanis. Exclusion of recommendations were primarily due to differences in the healthcare systems of Pakistan and the US, or the unavailability of certain drugs in Pakistan. Conclusion: A CPG for the management of T2DM in Pakistan was created. Our newly developed guideline recommends earlier screening for T2DM in Pakistan, primarily due to the higher prevalence of T2DM amongst younger individuals in Pakistan. Moreover, the systematic methodology used is a significant improvement on pre-existing T2DM CPGs in Pakistan. Once these evidence based CGPs are officially published, their nationwide uptake should be top priority. Our findings also highlight the need for rigorous expanded research exploring the effectiveness of earlier screening for T2DM in Pakistan.