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.

A Case Reported With 46, XX Testicular Disorders Of Sexual Development And Its Possible Association With Dysembryoplastic Neuroepithelial Tumour.

The main factor determining differentiation of bipotential gonads into testes or ovaries is the presence or absence of SRY (sex-determining region on Y chromosome) gene. De la Chapelle syndrome is a chromosomal anomaly with chromosomal makeup of a female (46, XX) and phenotypic presentation of a male. Previously known as XX sex reversal, it is now called 46, XX testicular disorders of sexual development (DSD). Although rare, it presents as a major chromosomal anomaly, with SRY gene crossover proposed as an underlying aetiology in most patients. We report the case of a 25-year-old male who presented with infertility and was diagnosed with De 46, XX testicular DSD. He has a previous history of resected dysembryoplastic neuroepithelial tumour (DNT). The differential diagnosis of 46, XX DSD and possible association/coincidental finding of DNT have been discussed. Karyotyping should be a part of the workup for every patient who presents with infertility and has azoospermia and hypergonadotropic hypogonadism.

Brown Tumour As An Unusual But Preventable Cause Of Spinal Cord Compression: Case Report And Literature Review.

Brown tumour is an infrequent, focal, and benign osteolytic lesion which is a consequence of abnormal bone metabolism in hyperparathyroidism (both primary and secondary). It is also known as Osteoclastoma. In the present era, we rarely encounter skeletal disease caused by primary hyperparathyroidism. Although it is a rare presentation because of advancement of treatment but still can be encountered because of lack of standard care so we should have high index of suspicion to avoid this preventable complication. We report here a case of brown tumour in the thoracic vertebra of a young female patient with End Stage Renal Disease, who presented with backache and bilateral lower limb weakness. MRI of the spine showed multiple non 20 enhancing abnormal signals involving vertebral body of C2, posterior elements of C6, and bilateral sacral vertebra, suggestive of healed fractures versus bone forming tumours. She underwent laminectomy. Her histopathology report was consistent with brown tumour of hyperparathyroidism.

Chronic Diarrhea: A rare presentation of Hodgkin's Lymphoma.

Hodgkin's Lymphoma is a cancer affecting the lymphatic system. There are two subtypes of Hodgkin's Lymphoma: Nodular lymphocyte predominant (NLPHL) and classical Hodgkin's Lymphoma which has further four types. It has a bimodal distribution and is more common among males. The most common presentation is painless swelling in the neck, armpit or groin region. Associated Symptoms include night sweats, unintentional weight loss, fever, persistent cough or dyspnea. Involvement of the gastrointestinal tract is a rare occurrence. Diagnosis is based on hematological, radiological and histochemical studies. Here we report a rare presentation of a 47-year-old male who presented with symptoms of loose stools, weight loss and fever. CT scan and abdominal lymph node biopsy findings were consistent with a lymphoproliferative disorder Patient was being managed in the line of malabsorption syndrome with possible underlying malignancy but his condition deterioted before the histological diagnosis was confirmed. Thus, this report highlights the importance having a consideration for Hodgkin's lymphoma in the management of chronic diarrhea.

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.

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.

Relationship Between Estimated Average Glucose (eAG) and Fasting Plasma Glucose in a Cohort of Pakistani Diabetic Subjects.

Introduction Scientific literature is scarce on the utility of estimated average glucose (eAG) from Pakistan. Hence, there is a dire need to evaluate the relationship between eAG and fasting plasma glucose (FPG), in order to enhance our understanding of eAG and its usefulness. This study aims to investigate the relationship between FPG and eAG in diabetic patients calculated using HbA1C. Materials and methods A retrospective study was conducted at the Aga Khan University, Karachi, Pakistan. The medical records of both genders in the age range of 18-60 years, presenting as outpatients at the endocrine clinic, labeled as DM, were reviewed from January 2013 to December 2019. The subjects were divided into three groups A (<130 mg/dL), B (130-179 mg/dL), and C (>180 mg/dL) based on FPG levels. A correlation was compared using Spearman's correlation. Box, whisker plots, and scatter plots were computed by R studio. Results After excluding those with missing values for either serum Cr, FPG, and HbA1c and sub-optimal renal function based on estimated glomerular filtration rate (eGFR) a total of 4,673 cases were analyzed. Subgroup A showed good glycemic control, whereas subgroup C showed poor glycemic control. The difference between eAG and FPG was significant (p < 0.0001). eAG values were found to be elevated than FPG values in groups A and B and almost the same in group C, whereas a moderately significant correlation with eAG and FPG in all three groups. Conclusion The correlation between eAG and FPG varies with blood glucose control and was significantly higher in the poorly controlled diabetes group. As the association between the FPG and eAG levels varies with the extent of blood glucose control, reporting eAG with HbA1c by a simple formula, at no additional cost will prove to be beneficial for clinical care.

Osteoporosis Complicating Renal Tubular Acidosis in Association With Sjogren's Syndrome.

Chronic metabolic acidosis increases alkali mobilization from the bone and promotes the development of osteoporosis. We report the case of a 35-year-old Caucasian female who presented for surgical fixation of a left femoral fracture sustained six months previously from a ground level fall with known primary hypothyroidism (for 12 years, on thyroxine replacement) with history of hypokalemia for the last 13 years (on regular oral potassium supplements). There was no history of fracture in past. There was no history of renal stones. There was positive history of hypokalemic periodic paralysis twice in past (12 and 13 years back). There was no history of recurrent oral or ocular ulcers. On examination there was no uveitis, oral ulcers, lacrimal or parotid gland enlargement. Upon workup the patient was diagnosed with left-sided femur fracture (neck) and was admitted for surgical management. She underwent left dynamic hip screw fixation under general anesthesia which she tolerated well. Upon further workup she had normal anion gap with hyperchloremic metabolic acidosis, low vitamin D level and dual-energy x-ray absorptiometry (DEXA) scan revealed osteoporosis at femur and hip joint. Vitamin D was replaced, she was started on Ibandronate and calcium supplements. Her further workup revealed positive anti-SSA. Our final clinical diagnosis in this case is possible or incomplete Sjogren's syndrome causing type-1 renal tu-bular acidosis (RTA; distal RTA) with osteoporosis.

Dengue fever presenting as quadriparesis due to hypokalaemia: a rare presentation.

Dengue is one of the leading causes of arthropod borne viral haemorrhagic fever. Majority of the times, it clinically manifests as fever, arthralgia and rash; however, we present a case of a young man who presented with progressively increasing weakness of all four limbs. Initial investigations showed low potassium, hence he was managed as hypokalaemic periodic paralysis. With initial history of fever and low platelets, dengue was suspected. Dengue antibody was checked which came out to be positive. Potassium was replaced which led to improvement in power of his limbs. He was discharged in a stable condition with a diagnosis of dengue with hypokalaemic quadriparesis.

Is It T3 Thyrotoxicosis? A Case of Falsely Elevated Tri-Iodothyronine (T3) Levels Leading to a Diagnosis of Multiple Myeloma.

We are presenting a case of falsely elevated T3 levels in a patient due to interference from monoclonal immunoglobulins. A 56-year-old, clinically euthyroid man referred to the endocrinology clinic of the Aga Khan university, Karachi Pakistan, for possible T3 thyrotoxicosis after thyroid function tests revealed total T3 >12.32 nmol/L (reference range 0.6-2.79), normal TSH, and total T4 level. There was a mismatch in clinical and laboratory parameters and preliminary laboratory results were suggestive of thyroid binding globulin abnormalities. Further evaluation in this context unmasked multiple myeloma. The presence of monoclonal immunoglobulins can lead to assay interference and spurious results. To the best of our knowledge, this is the second case defining the cause of falsely elevated T3 levels, due to assay interferences with binding of T3 only to monoclonal immunoglobulins.

Skin manifestations in diabetes mellitus.

Background: Diabetes mellitus affects all systems of the body. Skin is also frequently involved. The aim of the study was to assess the frequency of various skin manifestations in patients with diabetes mellitus. Methods: This descriptive study was conducted at the out-patient diabetic clinics at Aga Khan University Hospital, Karachi. One hundred consecutive patients, both male and female suffering from either type-1 or type-2 diabetes mellitus were included. Results: Out of hundred patients, skin changes were present in 84% of patients. The most frequent finding was skin infections present in 29.7% of patients and the second most common finding was diabetic dermopathy found in 28.5% of patients. Other finding were: Acanthosis Nigricans in 19%, sweating complications in 14.2%, nail involvement in 10.7%, oral involvenient in 5.9%, diabetic foot in 5.9%, xanthelasma in 4.7%, yellow skin in 1.1%, generalized Pruritus in 1.1%, limited joint mobility in 1.1%. Conclusion: The cutaneous manifestations are very common in our diabetic patients (84%) and it is important that they are identified and appropriately treated in diabetes follow up clinics.

Conversion of autoimmune hypothyroidism to hyperthyroidism.

BACKGROUND: Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. CASE PRESENTATION: We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. CONCLUSION: High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

Frequency of Streptococcus pneumonia and Haemophilus influenza in acute exacerbation of chronic obstructive airway disease and their sensitivity to levofloxacin.

OBJECTIVE: To determine the frequency of Streptococcus pneumoniae and Haemophilus influenzae in acute exacerbation of chronic obstructive pulmonary disease and their sensitivity to levofloxacin. METHODS: The cross-sectional study was conducted at the Department of Medicine, AbbasiShaheed Hospital, Karachi, between July 2009 and January 2010. Patients already diagnosed with chronic obstructive pulmonary disease and admitted with symptoms of acute exacerbation were included in the study and their sputum samples were sent for microbiological evaluation. SPSS 16 was used for statistical analysis. RESULTS: Of the total 105 patients in the study, 90 (85.17%) were males. Overall mean age at presentation was 62 +/- 10.2 years. S. pneumoniae was isolated from sputum culture of 33 (31.4%) patients, while 13 (12.4%) patients showed growth of H. influenzae. Out of the 33 sputum specimens of S. pneumoniae, 32 (97.0%) were sensitive to levofloxacin, while 1 (3.0%) was resistant. All the 13 isolates of H. influenzae were sensitive to levofloxacin. CONCLUSION: S. pneumoniae and H. influenzae are still the most prevalent organisms isolated in acute exacerbation of chronic obstructive pulmonary disease in our population. Levofloxacin is still considered a highly sensitive antibiotic against these common micro-organisms in our population, but S. pneumoniae has started developing resistance against levofloxacin. Therefore, intermittent surveillance regarding development of resistance pattern of common micro-organisms against commonly prescribed antibiotics is required.

Disappearance of pituitary macro adenoma with combination of ketoconazole and cabergoline treatment: an unusual case of Cushing's syndrome with interesting findings.

Cushing syndrome is associated with significant morbidity and mortality if left untreated because of associated metabolic and cardiovascular complications. An extremely ill patient with Cushing's syndrome caused by adrenocorticotropic hormone producing pituitary macro adenoma responded dramatically to ketoconazole and cabergoline treatment. His 4 month long medical treatment resulted in improvement of hypercotisolism clinically and biochemically and in complete disappearance of pituitary macro adenoma without any surgical intervention.