Association of pharmacogenomic, clinical and behavioural factors with oral levothyroxine (LT-4) dose of hypothyroid patients in Sri Lanka: a matched case control study.

BACKGROUND: Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. METHOD: This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. DISCUSSION: Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients.

Paraganglioma presenting as hypertension during pregnancy, proteinuria, thrombocytosis, and diabetes mellitus: a case report.

BACKGROUND: Paraganglioma is a very rare cause of pregnancy-induced hypertension. The objective of this case report is to present a case of paraganglioma presented during pregnancy and missed. Later, the diagnosis was made during the postpartum period because of persistence of hypertension. CASE PRESENTATION: Here, we describe the case of a patient with paraganglioma who initially presented with pregnancy-induced hypertension and gestational diabetes mellitus. She had persistence of hypertension and diabetes mellitus following delivery with proteinuria, thrombocytosis, and spells. Once her pelvic paraganglioma was removed, her blood pressure and blood sugar were normal without antihypertensives or hypoglycemic agents, respectively. Her proteinuria settled with near-normal platelet counts. CONCLUSION: Although neuroendocrine tumors are a rare cause of pregnancy-induced hypertension, it should be suspected in the appropriate clinical setting. Diabetes mellitus, proteinuria, and thrombocytosis can be a clinical feature in paraganglioma.

Laparoscopic Bilateral Adrenalectomy in a Young Female Patient with Recurrent Cushing's Disease.

INTRODUCTION: Synchronous bilateral adrenalectomy is undertaken less often due to numerous perioperative challenges and rare circumstances of patients needing this procedure. Bilateral adrenalectomy is an important second-line option for patients with persistent or recurrent hypercortisolism following transsphenoidal surgery for Cushing's disease. Here, we present a challenging case of synchronous laparoscopic bilateral adrenalectomy for a young female patient with recurrent Cushing's disease and fertility wishes. Case Presentation. A 21-year-old recently married patient who was diagnosed with Cushing's disease with a pituitary microadenoma had undergone two attempts of transsphenoidal excision of the pituitary tumour. Follow-up evaluation showed an unresectable residual tumour with invasion of the intracavernous part of the left internal carotid artery. As the patient had the hypothalamic-pituitary-ovarian axis intact with strong fertility wishes, she was offered bilateral adrenalectomy instead of radiotherapy. She was prepared for the surgery with close perioperative support from the endocrinology and anaesthesia teams. Intravenous hydrocortisone infusion was started at the induction of anaesthesia. Transperitoneal approach was used with the patient positioned in left and right lateral positions for right and left glands, respectively. A meticulous surgical technique was used for the identification of adrenal veins to clip them before division followed by handling of the glands. The patient had minimal haemodynamic disturbances during surgery. Intraoperative blood loss was less than 100 ml, and operative time was 220 minutes. She had a gradual recovery following postoperative respiratory distress due to basal atelectasis and consolidation. Cortisol levels were less than 20 nmol/L postoperatively, suggesting successful surgical intervention. Two months after surgery, she continued on maintenance therapy of oral hydrocortisone and fludrocortisone and was encouraged to go ahead with pregnancy. CONCLUSION: Although bilateral adrenalectomy is considered a high-risk procedure, these risks can be mitigated and performed safely while maintaining close multidisciplinary perioperative support.

A Practitioner's Toolkit for Insulin Motivation in Adults with Type 1 and Type 2 Diabetes Mellitus: Evidence-Based Recommendations from an International Expert Panel.

AIM: To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner's toolkit for insulin motivation in the management of diabetes mellitus (DM). BACKGROUND: Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization. REVIEW RESULTS: After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy. CONCLUSIONS: In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.

Comparison of glycaemic control and anthropometric parameters before and after Ramadan fasting in a selected cohort of patients with type 2 diabetes mellitus in Sri Lanka.

INTRODUCTION: The majority of Sri Lankan Moors fast during Ramadan. This may have an effect on their glycaemic control and anthropometric parameters. However, limited information exists about the impact of Ramadan fasting on diabetes in Sri Lanka. OBJECTIVES: The main objective of this study was to investigate the effect of Ramadan fasting on glycaemic control and anthropometric parameters in patients with type 2 diabetes mellitus (T2DM). Patients were also observed for symptoms of hypoglycaemia, timing and association with different antidiabetic agents. METHODS: One hundred and twenty Sri Lankan Moors with T2DM were recruited for this study. Biochemical investigations and anthropometric parameters were done before and after Ramadan fasting. The statistical analysis was done with paired t test to compare glycaemic control and anthropometric parameters before and after Ramadan. RESULTS: There was a significant decrease in body weight (mean body weight 66.17 to 65.52 kg; p= < 0.001) and waist circumference (93.84 to 92.16cm; p= < 0.001). However, the glycaemic control worsened in all patients during Ramadan with rise in mean fructosamine value of 354.1 to 996.9µmol/L. Out of 104 participants 43 participants experienced symptoms of hypoglycaemia. CONCLUSIONS: The current study showed an improvement in the body weight and waist circumference during Ramadan fasting, however the glycaemic control has been worsened. More follow-up studies are warranted in order to draw a conclusion on the effect of Ramadan fasting in glycaemic control and anthropometric parameters in diabetes patients.