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.

Evaluating Glycemic Control Efficacy and Safety of the Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis.

Introduction: Diabetes Mellitus (DM) is a significant global health concern, with Type 2 DM (T2DM) being highly prevalent. Glucagon-Like Peptide 1 receptor agonists (GLP-1RA), such as Danuglipron, offer potential benefits in T2DM management. This meta-analysis examines the safety and efficacy of Danuglipron, focusing on adverse outcomes and glycemic parameters. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane Library for RCTs involving Danuglipron till August 2023, following PRISMA guidelines. The Cochrane risk-of-bias tool was used for quality assessment. Adverse outcomes (diarrhea, nausea, vomiting, headache, decreased appetite, dyspepsia, dizziness) and glycemic parameters like changes in HbA1C, fasting plasma glucose (FPG), and body weight were analyzed. Results: Four RCTs published from 2021 to 2023 were included. Both doses of Danuglipron were associated with diarrhea (RR=2.66, 90% CI: 1.32 to 5.35, p=0.02), nausea (RR=5.5, 90% CI: 3.4 to 8.88, p<0.00001), and vomiting (RR=5.98, 90% CI: 2.93 to 12.23, p=0.0001). The 120mg dose showed decreased appetite (RR=3.46, 90% CI: 1.57 to 7.62, p=0.01), dyspepsia (RR=4.04, 90% CI: 1.93 to 8.43, p=0.002), and dizziness (RR=5.08, 90% CI: 1.45 to 17.82, p=0.03). Reductions in HbA1C (SMD -1.09, 90% CI -1.39 to -0.8, p < 0.00001), FPG (SMD -1.10, 90% CI -1.46 to -0.75, p < 0.00001), and body weight (SMD -1.08, 90% CI -1.42 to -0.74, p < 0.00001) were observed for both doses. Conclusion: Danuglipron demonstrates potential for glycemic control and weight reduction in T2DM. Adverse outcomes include diarrhea, nausea, vomiting, and decreased appetite, with dose-related effects. Clinicians must weigh benefits against side effects when considering Danuglipron for T2DM management.

Predicting the bracket bond failure rate in orthodontic patients: A retrospective cohort study.

The aim of this study was to determine the risk factors associated with orthodontic bracket bond failure and to develop a prediction equation for orthodontic bracket bond failure rate using the risk factors. This was a retrospective cohort study conducted on a sample of 690 brackets in orthodontic patients aged 10 to 28 years old (mean age 17.97±5.11 years old) visiting a dental hospital. The effect of various parameters of orthodontic bond strength was assessed on bracket failure rate using survival analysis. Parametric (exponential) regression analysis was used to determine the risk factors associated with bracket failure and a prediction equation was formulated to predict the bracket failure rate. The overall mean survival time for the brackets was 3.04 (2.9-3.17) years. The univariate analysis showed a statistically significant (P<0.05) association of bracket material, site, overjet, overbite, incisor and molar classification and age. The multivariate analysis showed a significant interaction between site and side along with bracket material, jaw, overjet and overbite in the model. The risk of bracket failure on the right posterior region is 7.7 times that in the right anterior region when adjusted for all other variables in the model (HR: 7.7; 95% CI: 4.3-13.6). The model including bracket material, jaw, overjet, overbite and interaction between site and side can be used as a predictor of hazard rate for orthodontic bracket failure. Care should be taken in bonding brackets in the posterior region, as their debonding rate is higher as compared to anterior region.

Case report: lady with bone pains for 5 years-parathyroid carcinoma.

BACKGROUND: Parathyroid cancer is a rare cause of primary hyperparathyroidism. It presents a diagnostic and therapeutic challenge that may not be recognized preoperatively, and is often not conclusively identified during the operation. We present the case of a lady with backache and hypercalcemia, but with inadequate work-up for her condition for several years. CASE PRESENTATION: A middle aged lady of Asian descent presented with backache. Initial work up revealed mild hypercalcemia, negative work up for multiple myeloma, negative sestamibi scan for parathyroid pathology. A phenomenally elevated parathormone (PTH) level-2105 pg/mL (16-87 pg/mL), and rising serum calcium, 15.1 mg/dL, (8.6-10.5 mg/dL), ordered years later prompted a repeat sestamibi scan and ultrasonography of neck. Based on these investigations, a diagnosis of primary hyperparathyroidism, with high suspicion of parathyroid cancer was made. The patient underwent surgical tumour resection, with subsequent histopathological confirmation of diagnosis. CONCLUSION: In the setting of hypercalcemia, PTH level assessment is a must. This helps to differentiate between the parathyroid dependant and independent causes of high serum calcium, thereby encouraging a comprehensive pathway to the work up of the cause of hypercalcemia. The parathyroid cancer is a very rare cause of hypercalcemia, which needs to be considered in the differentials of primary hyperparathyroidism, particularly in the setting of high PTH levels.

Unusual presentation with polymenorrhagia and markedly high 17-hydroxy progesterone levels in a lady with Non-Classic Congenital Adrenal Hyperplasia.

Congenital adrenal hyperplasia is generally associated with oligo-amenorrhea, and its presentation with polymenorrhagia is rare. Here we present a case of an Asian female who presented with polymenorrhagia since menarche, increased body hair growth and enlargement of clitoris for 7-8 years. Examination revealed a normal Body Mass Index, moderate hirsutism, Tanner 5 breasts and significant clitoromegaly. Serum testosterone and 17-hydroxyprogesterone levels were elevated. Ultrasonography revealed normal adrenal glands and polycystic ovaries. adrenocorticotropic hormone stimulation test uncovered borderline cortisol deficiency. Oral dexamethasone was commenced and six months later, she showed improvement though there was no change in hirsutism or clitoromegaly. The case is unique because it presented with polymenorrhagia. Also, such phenomenally high 17-hydroxyprogesterone levels are not expected in non-classic congenital adrenal hyperplasia.

Case report: nocardia infection associated with ectopic cushings.

BACKGROUND: Cushing's syndrome results from exposure to excess glucocorticoids. Ectopic Cushings is endogenous ACTH dependant form of Cushing's associated with markedly raised ACTH and cortisol levels. This leads to an impaired immune response, setting the stage for occurrence of opportunistic infections. Nocardiosis is a gram positive bacterial infection caused by aerobic actinomycetes in genus Nocardia. We report a series of patients diagnosed with ectopic Cushings, having pneumonia with Nocardia spp. In one of these cases, the manifestations of Cushing's disappeared with treatment for Nocardia. CASE PRESENTATION: Two middle aged men of Asian descent presented to the Endocrine clinic: the first with history of exertional shortness of breath, and weight loss for 1 year, the other with facial swelling, disturbed sleep and lethargy for a month. The third case was a young Asian male who presented with progressive weakness & weight loss for 2 months. All three patients had uncontrolled hypertension, high blood sugars & were hypokalemic (K: 2.52, 2.9, 1.5 mmol/l); 24 hour urine cortisol was elevated at 2000, 27216 and 9088 (32-243 ug/24 hours); ACTH 68.5, 159, 255 [0-48 pg/ml), respectively. Their MRI pituitary was normal, inferior petrosal sinus sampling revealed no central peripheral gradient. CT chest of these subjects demonstrated cavitatory lung lesions; microscopic analysis of respiratory samples was suggestive of infection with Nocardia spp. Histopathology of bronchoscopic-guided biopsy revealed no malignancy. Antihypertensives, insulin, potassium replacement, ketoconazole & trimethoprim-sulphamethoxazole (TS) were initiated. The patients' symptomatology improved & cavitatory lesions resolved with treatment. The primary source for the ectopic cushings remained unknown. The first case required bilateral adrenalectomy. The second case followed a progressively downhill course leading to death. In the third case, we were able to completely taper off ketoconazole, potassium, insulin & antihypertensives, after starting TS. CONCLUSION: Opportunistic infections are known to be associated with Cushing's syndrome, and higher levels of glucocorticoid secretion are found in patients with ectopically produced ACTH. Pulmonary nocardiosis is important differential to consider. This series includes the first case reported in which signs and symptoms of cushings subsided after treatment of Nocardia.

Middle aged male with pulmonary tuberculosis and refractory hypercalcemia at a tertiary care centre in South East Asia: a case report.

55-year male of Asian descent presented with weight loss, lethargy, drowsiness and low grade fever without cough. Examination revealed crackles in the chest but no focal neurological deficit. Chest X ray revealed an infiltrate consistent with tuberculosis. Biopsy of infiltrate was negative for malignancy. Corrected calcium level revealed parathyroid independent hypercalcemia. Further diagnostic work up for drowsiness and hypercalcemia was normal. Despite receiving hydration and pharmacotherapy for his hypercalcemia, his condition failed to improve. When steroids were started, the patient's calcium levels and symptomatology resolved. Tuberculosis causing hypercalcemia is uncommon. Steroids are useful agents, particularly in refractory cases.

Etiology, functional status and short term outcome of patients with pituitary lesions. An experience from a developing country.

OBJECTIVE: To describe the etiology, functional status and short term outcome of patients with pituitary lesions (PL). METHODS: Brain or pituitary MRI reports of 3753 patients were analyzed for PL over the period of 2000 to 2007, done at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. MRIs with reported PL and all those ordered by Endocrinologists with or without pituitary abnormalities, were included in the analysis. This made a total of 338 (9%) MRI reports. PL were defined as pituitary tumors, cysts, haemorrhage, hypoplasia; and empty sella. Patients with these PL, were analyzed for symptoms, hormonal profile and short term outcome in the hospital retrospectively. RESULTS: In the analysis of 338 MRI reports, 23% had normal pituitary gland on MRI examination. Hypogonadotrophic hypogonadism was the commonest (38.5%) endocrine abnormality seen with normal pituitary MRI, followed by hypopituitarism (5.1%). Most common PL identified were macroadenoma (38.7%), empty sella (16.5%) and microadenoma (12.7%). Patients with macroadenoma had 58% of non-functional tumours while 19.1% had hypopituitrism, 17.6% had acromegaly and 17.5% had prolactinoma. Majority of these lesions were causing headache and visual symptoms (42.7%) and were treated with surgery (75.5%). Patients with microadenoma included 39.5% prolactinomas, 18.6% cushing disease, 14% acromegaly, 4.7% hypogonadotrophic hypogonadism and 2.3% hypopituitrism. Majority of these lesions were treated with drugs and 37.3% were treated with surgery. In empty sella patients, 32% patients had endocrine abnormalities among which 21.4% had hypopituitrism, 2% had hypogonadotrophic hypogonadism, and only 6% patients had normal endocrine workup. A significant number of patients (62.5%) never had endocrine hormonal checkup. CONCLUSION: Although PL are less common entities (9% in 3,753 reports) but they are associated with significant endocrinal abnormalities and need prompt treatment. Empty sella, which is not considered as a distinct abnormality, is also associated with significant endocrine deficiencies.