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.

Nanozymes and carbon-dots based nanoplatforms for cancer imaging, diagnosis and therapeutics: Current trends and challenges.

Cancer patients face a significant clinical and socio-economic burden due to increased incidence, mortality, and poor survival. Factors like late diagnosis, recurrence, drug resistance, severe side effects, and poor bioavailability limit the scope of current therapies. There is a need for novel, cost-effective, and safe diagnostic methods, therapeutics to overcome recurrence and drug resistance, and drug delivery vehicles with enhanced bioavailability and less off-site toxicity. Advanced nanomaterial-based research is aiding cancer biologists by providing solutions for issues like hypoxia, tumor microenvironment, low stability, poor penetration, target non-specificity, and rapid drug clearance. Currently, nanozymes and carbon-dots are attractive due to their low cost, high catalytic activity, biocompatibility, and lower toxicity. Nanozymes and carbon-dots are increasingly used in imaging, biosensing, diagnosis, and targeted cancer therapy. Integrating these materials with advanced diagnostic tools like CT scans and MRIs can aid in clinical decision-making and enhance the effectiveness of chemotherapy, photothermal, photodynamic, and sonodynamic therapies, with minimal invasion and reduced collateral effects.

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.

An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight.

The novel pathogenic virus was discovered in Wuhan, China (December 2019), and quickly spread throughout the world. Further analysis revealed that the pathogenic strain of virus was corona but it was distinct from other coronavirus strains, and thus it was renamed 2019-nCoV or SARS-CoV-2. This coronavirus shares many characteristics with other coronaviruses, including SARS-CoV and MERS-CoV. The clinical manifestations raised in the form of a cytokine storm trigger a complicated spectrum of pathophysiological changes that include cardiovascular, kidney, and liver problems. The lack of an effective treatment strategy has imposed a health and socio-economic burden. Even though the mortality rate of patients with this disease is lower, since it is judged to be the most contagious, it is considered more lethal. Globally, the researchers are continuously engaged to develop and identify possible preventive and therapeutic regimens for the management of disease. Notably, to combat SARS-CoV-2, various vaccine types have been developed and are currently being tested in clinical trials; these have also been used as a health emergency during a pandemic. Despite this, many old antiviral and other drugs (such as chloroquine/hydroxychloroquine, corticosteroids, and so on) are still used in various countries as emergency medicine. Plant-based products have been reported to be safe as alternative options for several infectious and non-infectious diseases, as many of them showed chemopreventive and chemotherapeutic effects in the case of tuberculosis, cancer, malaria, diabetes, cardiac problems, and others. Therefore, plant-derived products may play crucial roles in improving health for a variety of ailments by providing a variety of effective cures. Due to current therapeutic repurposing efforts against this newly discovered virus, we attempted to outline many plant-based compounds in this review to aid in the fight against SARS-CoV-2.

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.

Primary thyroid lymphoma: Case series of patients from a developing country.

Primary Thyroid Lymphoma (PTL) is a rare disease, mostly affecting middle-to-old aged females. It has a strong association with pre-existing thyroiditis, which increases the risk of its development. The disease has been studied in detail in the Western populations. However, there is lack of data for south Asians, especially in Pakistani population. This study was carried out to learn more about the disease characteristics in our area. This was a retrospective study where we reviewed four diagnosed and/or treated cases of primary thyroid Lymphoma at tertiary care hospital of Pakistan (Aga Khan University Hospital), Karachi, Pakistan. Each patient's medical record was reviewed and studied. The participants' average age was 62.8±10.12 years,, with two males and two females. The histology of all of the patients was compatible with the Diffuse B cell Lymphoma subtype. One patient died as a result of complications, one patient was lost to follow up, and the remaining two patients are doing well with no active complaints and are being followed up on a regular basis.

Association of thyroid antibodies status on the outcomes of pregnant women with hypothyroidism (maternal hypothyroidism on pregnancy outcomes, MHPO-4).

BACKGROUND: Autoimmunity increases with age and is often commonly evaluated in women of the reproductive age group. Prevalence of thyroid antibodies is common even in euthyroid pregnant women. We aim to compare the association of thyroid antibody status on the maternal and neonatal outcomes in pregnant women with hypothyroidism. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital. Information was collected on pregnant women who have been diagnosed with hypothyroidism before conception or during their antenatal period. Laboratory data were recorded for thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid-stimulating hormone levels. Maternal and neonatal outcomes were also noted from medical file records. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Overall, 146 out 718 cases were included for final analysis. Thyroid peroxidase antibodies were positive in 66.4% and anti-thyroglobulin was positive in 52.1% cases, whereas 43.8% of cases had both antibodies positive. Pre-gestational diabetes was significantly associated with thyroid autoimmunity. There was a 73% less chance of gestational hypertension for thyroid autoimmune groups. Gestational diabetes and maternal (chronic) hypertension were found to have an independent effect on postpartum hemorrhage. Hypertensive disorders in pregnancy were found to have an independent risk for premature birth. CONCLUSION: Our study reports a 74.7% prevalence of positive thyroid antibodies in hypothyroid pregnant women, with higher association with pre-gestational diabetes. Gestational hypertension was least likely to occur in thyroid autoimmune groups. None of the outcomes were independently associated with worse outcomes.

Lack of association of HFE gene polymorphism with high body iron status in Pakistani patients with type 2 diabetes mellitus.

OBJECTIVE: The Aim of this study was to investigate the relationship of 3 common polymorphisms in the HFE gene (C282Y, H63D and S65C) with high body iron status in a population of Pakistani subjects with type 2 diabetes mellitus (DM) and to explore if there is any novel mutation in HFE gene in a sample of Pakistani subjects with type 2 DM. METHODS: In a case-control design, 200 healthy controls and 200 consecutive adult subjects with type 2 DM (both gender; age range of 30-70 years) were enrolled with informed consent. Their serum samples were analyzed for body iron status (ratio of concentration of soluble transferrin receptor to ferritin concentration). DNA from blood was screened for HFE gene polymorphisms via polymerase chain reaction, followed by restriction fragment length polymorphism or via Sanger sequencing to identify any novel mutation(s) in HFE gene. RESULTS: We found that there was lack of any association between HFE polymorphism and body iron status in Pakistani subjects with type 2 DM and healthy controls. H63D was the most common polymorphism found in this population. Single base substitution of G nucleotide instead of C at the codon position 187 in the HFE gene exon 2 was discovered in one subject with DM. There was also a lack of association between D allele (variant allele of H63D) and type 2 DM. A significant relationship was found between CG genotype and abnormal albuminuria in subjects with type 2 DM (p = 0.036). CONCLUSION: In conclusion, HFE gene polymorphism is not associated either with high body iron status or type 2 DM in a hospital based Pakistani population and variant allele of H63D polymorphism appears to be associated with diabetic nephropathy.

Clinical outcomes of Sodium-glucose cotransporter-2 inhibitors in patients with Type 2 Diabetes Mellitus: An observational study from Pakistan.

OBJECTIVE: To determine the efficacy and safety of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) use in the Pakistani population. METHODS: Retrospective review of initial 100 patients who were prescribed with any agent of the SGLT2i group from July 1, 2018, to January 2019 at Aga Khan University Hospital, Karachi. SGLT2i was offered to patients of above 18 years of age with inadequate glycemic control on existing antidiabetic agents. Changes in HbA1c, the Body Mass Index (BMI), serum creatinine, any decrease in the requirement of insulin and sulphonylurea dose along with any side effects reported by the patients on follow-up visits. RESULTS: Most study participants were females (56%) with the mean age of 52±10 years. Substantial changes were observed in the HbA1c (7.5±1.1%, 7.9±1.2% from 8.7±1.5%, p < 0.01), BMI (31.4±5.8, 31.8±5.8 from 32.4±5.9kg/m2, p < 0.01) and in creatinine (0.71±0.1, 0.75±0.1 from 0.79±0.1 mg/dl, p < 0.01) at three and six months of follow up visits. The reduction in insulin and sulphonylurea doses was also significant. Adverse drug events that led to drug discontinuation in 14 individuals were, Urinary tract infection (UTI) (seven patients), Genital infection (three patients), nausea +UTI, abdominal pain +UTI, mild Diabetic Ketoacidosis, and polyuria (one patient each). None reported Fournier's gangrene, limb amputation, or fracture. CONCLUSION: SGLT2i significantly improved glycemic control, BMI, and serum creatinine in the Pakistani population with a very low number of observed adverse events.

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.

Localizing an occult insulinoma by selective calcium arterial stimulation test: first ever experience and a new dimension to diagnosis in Pakistan.

Insulinomas are rare, usually benign, solitary tumours accounting for 60% of islet cell tumours. These tumours can be difficult to localize preoperatively due to their small size. We present a challenging case of a 40 year old male with frequent hypoglycaemic spells and endogenous hypoglycaemia who presented as a diagnostic dilemma. Patient had an occult insulinoma with inconclusive CT Abdomen, MRI Abdomen and Octreotide scan. The final localization of the tumour was made by selective arterial calcium stimulation testing (SCAT), done for the first time in Pakistan at Aga Khan University Hospital. This was followed by successful distal pancreatectomy as localizd by SACT yielding a well differentiated neuroendocrine tumour. After surgery patient made a robust recovery with no further hypoglycaemic symptoms. Hence successful localization and management of occult insulinomas can be challenging but can be achieved with the advent of newer invasive modalities.

Primary Hyperparathyroidism: Experience from a Tertiary Care Centre in Pakistan.

OBJECTIVE: To study the clinical, biochemical and radiological features and management outcomes of patients with primary hyperparathyroidism. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, Pakistan and comprised data of patients with primary hyperparathyroidism from 2008 to 2017. RESULTS: Out of 103 patients, 83(80.6%) were female. Overall mean age was 59.3±16.2 years. Musculoskeletal manifestations were seen in 60(58.3%) patients and renal manifestations in 28(27.2%). Ostieits fibrosa cystica was found in 04(3.88%) patients. Overall, Ultrasound neck and sestamibi scan localized the lesion in 66 (64.1%) and 77 (76.2%) patients respectively. Among 79 patients who underwent surgery, 67 (84.8%) patients had an adenoma, 05 (6.3%) had hyperplasia and 02(2.53%) patients had parathyroid carcinoma whereas histopathology was inconclusive in 5 (6.32%) out of the 79 surgically treated patients. Disease recurrence was seen in 13 out of 79(16.45%) patients who underwent surgery. CONCLUSION: Primary hyperparathyroidism is associated with significant morbidity in our population. Targeted measures like improving patient awareness, routine calcium screening, vitamin D supplementation and a high index of suspicion by the clinician may help in early diagnosis of the condition and thus reduce morbidity.

Non Invasive Follicular Thyroid Neoplasm with Papillary like nuclear features (NIFTP), A time for change in Pakistan.

OBJECTIVE: To determine the cases of Noninvasive Follicular thyroid neoplasm with papillary like nuclear features (NIFTP) in Pakistani population retrospectively. Another objective was to determine their clinical and radiological outcomes with respect to local and systemic disease recurrence, reconfirming the benign course of this new nomenclature in Thyroid tumors by WHO in our population would encourage adopting the new conservative treatment approach in such patients. METHODS: This is a retrospective cohort study conducted at a tertiary care center in Karachi, Pakistan from 2007-2016. All follicular Variant papillary thyroid cancer (FVPTC) reported from a single institute had their histopathology slides reexamined for diagnosing NIFTP as per the new WHO criteria. These cases were then followed retrospectively from their diagnosis onset through their medical and electronic health record for any local or systemic disease recurrence. RESULTS: There were 199 cases of Papillary Thyroid cancer (PTC) which included 22 cases of FVPTC. Eleven cases fulfilled NIFTP criteria with tumor size ranging from 1.1cm to ≥ 5.5cm. All patients in the NIFTP group underwent total thyroidectomy. Nine patients (81.81%) received RAI131 therapy. Four (45%) patients had a median follow up of three to four years. There was no disease recurrence seen on both ultrasound and RAI scans of patients in the NIFTP group. Seven patients (87.5%) had normal surveillance thyroglobulin levels except one whereas three patients were lost to follow up. There was no disease recurrence seen both radiologically and biochemically in the NIFTP group. CONCLUSION: Our study favors the low risk nature of NIFTP with no disease recurrence in the cases studied and encourages de-escalation of treatment.

Efficacy of Liraglutide in clinical practice: Single centre experience.

BACKGROUND AND OBJECTIVE: GLP-one receptor agonists are amongst the unique antidiabetes medications that have significant metabolic and cardiovascular benefits in addition to glucose lowering effect. To best of our knowledge, there is no published data on efficacy of liraglutide use among Pakistani population.Our objective was to ascertain the efficacy of liraglutide use among type two diabetes patients. METHODS: This retrospective study was conducted at the Endocrinology Clinics of Aga Khan University Hospital (AKUH) Karachi, Pakistan during the period from July 01, 2016 to 30th June, 2017. Liraglutide was prescribed to 68 obese type two diabetes patients with uncontrolled diabetes taking more than one oral medication ± insulin. Starting dose of Liraglutide was 0.6 mg, which was increased to 1.2 mg after 1-2 weeks with further increment to 1.8 mg/day based on tolerance and individual patient preference. Dose of other diabetes medications was adjusted according to clinical judgment whereas Dipeptidyl peptidase-4(DPP-4) inhibitors were discontinued. RESULTS: Mean age of cohort was 55 years (SD=10.94 years) with median body mass index of 36.45 kg/m2 and majority (57.35%) were on a dose of 1.2 mg of Liraglutide per day. Median HbA1c reduced to 7.50% and 7.40% at three months and six months respectively vs 8.45% at baseline. Mean reduction in weight after three month was two kilograms and at six months, it was 1.38 kilograms respectively. CONCLUSION: Liraglutide as add on therapy demonstrated favourable HbA1c and weight reduction in obese uncontrolled type two Diabetes Pakistani subjects.

Ovalbumin self-assembles into amyloid nanosheets that elicit immune responses and facilitate sustained drug release.

Amyloids are associated with many neurodegenerative diseases, motivating investigations into their structure and function. Although not linked to a specific disease, albumins have been reported to form many structural aggregates. We were interested in investigating host immune responses to amyloid fibrils assembled from the model protein ovalbumin. Surprisingly, upon subjecting ovalbumin to standard denaturing conditions, we encountered giant protein nanosheets harboring amyloid-like features and hypothesized that these nanosheets might have potential in clinical or therapeutic applications. We found that the nanosheets, without the administration of any additional adjuvant, evoked a strong antibody response in mice that was higher than that observed for native ovalbumin. This suggests that amyloid nanosheets have a self-adjuvanting property. The nanosheet-induced immune response was helper T cell 2 (Th2) biased and negligibly inflammatory. While testing whether the nanosheets might form depots for the sustained release of precursor proteins, we did observe release of ovalbumin that mimicked the conformation of native protein. Moreover, the nanosheets could load the anticancer drug doxorubicin and release it in a slow and sustained manner. Taken together, our results suggest that amyloid nanosheets should be further investigated as either an antigen delivery vehicle or a multifunctional antigen and drug co-delivery system, with potential applications in simultaneous immunotherapy and chemotherapy.

Maternal characteristics and outcomes affected by hypothyroidism during pregnancy (maternal hypothyroidism on pregnancy outcomes, MHPO-1).

BACKGROUND: Hypothyroidism in pregnancy is an arena of ongoing research, with international conflicts regarding screening, management, and outcomes. Various studies have described the outcomes depending on geographical and international diagnostic criteria. No study has been conducted in this regard from the region of Pakistan. Therefore, we aim to report the clinical features and maternal outcomes of hypothyroid pregnancies and compare the maternal outcomes between uncontrolled and controlled TSH levels in the preconception as well as the gestational period. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital after ethical approval. We collected information on pregnant females who have diagnosed hypothyroidism before conception or during their antenatal period. We noted the maternal characteristics and maternal comorbidities. Laboratory data were recorded for thyroid stimulating hormone levels before conception and during gestation. We recorded maternal outcomes as pregnancy loss (including miscarriage, stillbirth/intrauterine death, medical termination of pregnancy and ectopic pregnancy), gestational hypertension, pre-eclampsia, postpartum hemorrhage, placental abruption, and modalities of delivery. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Among 708 hypothyroid women 638 had live births. Postpartum hemorrhage was the most frequent maternal outcome (38.8%). The emergency cesarean section occurred in 23.4% of cases. We determined TSH levels in 53.2, 56.7, 61.7 and 66.6% of cases in preconception, 1st, 2nd, and 3rd trimester periods. A significant association existed between cesarean section and preconception thyrotropin levels > 2.5 mIU/L, whereas postpartum hemorrhage was significantly associated with thyrotropin levels > 2.5 mIU/L in the preconception and third trimester. CONCLUSION: Successful live births in our patients were complicated by maternal postpartum hemorrhage and a frequent number of emergency cesarean section.

Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective.

Sodium-glucose co-transporter type 2 inhibitors (SGLT 2- i)are increasingly being used in the management of type 2 diabetes mellitus (T2DM). With the novel insulinindependent glycosuric action, these agents help to attain glycaemic goals by lowering HbA1c and fasting blood glucose. In addition, these agents improve metabolic control in diabetes and ameliorate comorbidities like obesity and hyper tension. Beneficial effec ts on cardiovascular outcomes have been a key attraction for physicians. These agents are used alone or in combination with oral antidiabetic agents and insulin to attain glycaemic and metabolic targets. A major disadvantagewith these agents is the increased risk for genital andurinary infections. When used in appropriate settings, there is no additional increased risk of hypoglycaemia or volume depletion with these agents. Available evidence suggests good efficacy and safety of these agents in diabetes management. The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles.

Cardiovascular disease risk factors in Pakistani population with newly diagnosed Type 2 diabetes mellitus: A cross-sectional study of selected family practitioner clinics in four provinces of Pakistan (CardiP Study).

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.

Pre-operative serum TSH levels: A risk factor for advanced metastatic differentiated thyroid carcinoma.

BACKGROUND AND OBJECTIVE: As the thyroid cancer incidence is increasing, the search for its risk factor is becoming more important. Serum thyroid stimulating hormone (TSH) levels being a growth factor for normal thyroid tissue, is also considered as growth promotor of cancer cells. In our study we aimed for pre-operative serum TSH levels of Differentiated thyroid cancers (DTC) done before their first surgery and determined its association with advanced disease in terms of stage, multifocal disease, lymph node involvement and distant metastasis. METHODS: We have conducted a retrospective review of thyroid cancers from 1st January 2008 to 31st December 2017. Out of 281, 142 cases were included according to inclusion criteria. We noted the demographic details of participants, their histopathological diagnosis and serum TSH levels done before first surgery from the medical records. We calculated the stage of tumor through modified American Joint Committee (AJCC) staging system. RESULTS: Out of 147 participants, 89.4% had papillary carcinoma or its variants whereas 10.6% reported follicular carcinoma. The mean pre-op TSH level of the patients included was 2.04 ± 1.79. In addition to the descriptive analysis, the univariate regression analysis revealed that the association of serum TSH levels was found to be statistically insignificant with advanced stage of thyroid cancer, multifocal disease, lymph node metastasis and distant metastasis respectively. CONCLUSION: The serum TSH levels before surgery was not associated with poor prognosis of differentiated thyroid cancer with respect to higher staging, multifocal disease, lymphatic or distant metastasis.

Morning cortisol as an alternative to Short Synecthan test for the diagnosis of primary adrenal insufficiency.

OBJECTIVE: To determine 7-9 am serum cortisol less than 5mcg/dl is an independent reliable confirmatory test for the diagnosis of primary adrenal insufficiency (PAI). METHODS: A total of 164 patients who visited the outpatient or inpatient department of Aga Khan University Hospital from June 2011 to June 2017 were included for the study. All those patients whose levels came out less than 5mcg/dl were recruited for the study and they all underwent SST. Other demographic and laboratory data were also recorded. RESULTS: The sensitivity of morning cortisol for diagnosis of PAI is 100% if levels are <1mcg/dl and decreases to 71.88% if levels are up to 5mcg/dl. CONCLUSION: Morning cortisol is sensitive enough as an alternative to SST if levels are <1mcg/dl (100%). However, if the levels are increased from > 1mcg/dl to < 5 mcg/dl, the sensitivity decreases gradually from 98% to 71%.