Endocrine System Disorders PDF Lecture Notes

SIT Internal Topic: Endocrine System Disorders Guest lecturer Dr Kristy Tian is an Associate Consultant at the Department of Endocrinology, SGH. She obtained her MBBS from Yong Loo Lin Schoo...

SIT Internal Topic: Endocrine System Disorders Guest lecturer Dr Kristy Tian is an Associate Consultant at the Department of Endocrinology, SGH. She obtained her MBBS from Yong Loo Lin School of Medicine, National University of Singapore in 2017 and later obtained her MRCP(UK) and M.Med (Internal Medicine) in 2019. She completed her specialist training in Endocrinology at Singapore General Hospital in 2023. Learning outcomes Upon completing the pre-readings and the lecture, you should be able to 1) Explain the pathophysiology, diagnosis, system complications and management of patients with diabetes 2) Discuss pathophysiology, diagnosis and management of patients with thyroid disorders 3) Relate the above to your professional practice and your roles in the interdisciplinary care of patients Resources VanMeter, K. C., & Hubert, R. J. (2014). Gould's Pathophysiology for the Health Professions (5th Ed.). Philadelphia, PA: Saunders. Cp 16: Endocrine system disorders. pg 403-415 Singapore MOH (2014). Clinical Practice Guideline on Diabetes Mellitus https://www.moh.gov.sg/hpp/doctors/guidelines/GuidelineDetails/cpgmed_diabetes_ mellitus MOH ACE Clinical Guidance (ACG) on optimizing management of type 2 diabetes mellitus by personalising selection of non-insulin T2DM medications based on patient comorbidities and risk factors, in particular cardiovascular and renal factors (2023) https://www.ace-hta.gov.sg/healthcare-professionals/ace-clinical-guidances- (acgs)/details/t2dm-personalising-medications American Diabetes Association Standards of Care https://diabetesjournals.org/care/issue/47/Supplement_1 1 16 Aug 2024  SIT Internal American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis https://www.liebertpub.com/doi/pdf/10.1089/thy.2016.0229 American Thyroid Association Guidelines for the Treatment of Hypothyroidism https://www.liebertpub.com/doi/full/10.1089/thy.2014.0028 2 16 Aug 2024  SIT Internal Pre-readings Diabetes Mellitus Diabetes is characterised by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both. Function of insulin Transports glucose, amino acids and potassium into cells Regulates how the body uses and stores glucose and fat Many body cells rely on insulin to take up glucose from the blood for energy However, some tissues can transport glucose in the absence of insulin o CNS (brain cells) o Digestive tract – insulin is not needed for glucose absorption o Kidneys o Myocardium o Exercising skeletal muscle – does not need a proportional amount of insulin Classification Type 1 diabetes mellitus o Due to autoimmune B-cell destruction, usually leading to absolute insulin deficiency Type 2 diabetes mellitus o Characterized by a combination of insulin resistance and inadequate compensatory insulin secretory response o Often associated with obesity, sedentary lifestyle and genetic factors Specific types of DM due to other causes o Diseases of the exocrine pancreas (cystic fibrosis, pancreatitis) o Drug induced DM Gestational diabetes mellitus o DM diagnosed in the 2nd or 3rd trimester of pregnancy that was not clearly overt DM prior to gestation Type 1 Type 2 Presentation More severe form Milder form, a component of metabolic syndrome Age at onset Children and adolescents Adults >50 years Onset Acute Insidious Etiology Autoimmune destruction Familial of pancreatic beta cells Obesity Familial history Lifestyle and environmental factors Treatment Insulin Lifestyle modifications: diet, exercise Oral hypoglycaemic agents 3 16 Aug 2024  SIT Internal Injectable agents: insulin, GLP 1 receptor agonists Acute Frequent Less common complications (hypoglycemia / ketoacidosis) Diagnostic criteria for DM Random plasma glucose ≥11.1mol/L 2-hour post 75g glucose load ≥11.1mmol/L Fasting plasma glucose ≥7.0mmol/L Glycemic Goals Hba1c is the primary tool for assessing glycemic status, and is strongly linked to diabetes complications Hba1c reflects average glycemia over approximately 2-3 months Factors that affect hemoglobin or red blood cell characteristics or turnover may affect Hba1c A Hba1c goal for many non-pregnant adults of 35 inches in women) 2) Plasma triglycerides > 150mg/dL 3) Plasma HDL cholesterol < 40mg/dL (men) or < 50 mg/dL (women) 4) BP > 130/85 mmHg, or on antihypertensive treatment 5) Fasting plasma glucose > 100mg/dL or on DM medications 11 16 Aug 2024  SIT Internal Hypothalamic pituitary thyroid axis William’s Textbook of Endocrinology Hypothalamus o Produces thyrotropin releasing hormone (TRH), which is synthesized in the paraventricular nucleus o TRH is released and transported to the anterior pituitary Pituitary gland o TRH stimulates the anterior pituitary to secrete thyroid stimulating hormone (TSH) o TSH enters the blood stream and acts on the thyroid gland Thyroid gland o TSH stimulates the thyroid gland to produce and release thyroid hormones o T4 is the predominant hormone released, but it is converted to the more active T3 in peripheral tissues Negative feedback o T3 and T4 exert negative feedback on both the hypothalamus and the pituitary gland Primary Hyperthyroidism Characterised by the overproduction and secretion of thyroid hormones by the thyroid gland, leading to suppressed levels of TSH Causes o Toxic adenoma o Toxic multinodular goiter o Graves’ disease o Destructive thyroiditis 12 16 Aug 2024  SIT Internal o Medication induced o Factitious thyroiditis Clinical presentation o Unintentional weight loss o Tachycardia or palpitations o Heat intolerance o Diarrhea o Anxiety Investigations show low/undetectable TSH levels with elevated thyroid hormone levels Treatment of Graves’ Disease Anti-thyroid Drugs Types o Methimazole: long half-life hence can be given once daily o Propylthiouracil: short half-life, blocks T4 to T3 conversion Minor toxicities (5-10%) o Rash ▪ May be managed with concurrent antihistamine therapy without stopping the medication ▪ Can consider changing to the alternative (50% cross reactivity) or consider definitive therapy Major toxicities o Agranulocytosis (absolute neutrophil count 5x ULN should prompt serious reconsideration of initiating ATD treatment o ANCA positive vasculitis Definitive Therapy Thyroidectomy Radioiodine Thyroid Storm Life-threatening endocrine emergency characterized by exaggerated symptoms of hyperthyroidism and evidence of multiorgan decompensation Burch-Wartofsky diagnostic scoring system for thyroid storm 13 16 Aug 2024  SIT Internal Management 1. Acute stabilization of the patient Ensure airway, breathing and circulation 2. Thyroid specific therapy with the goals to: Decrease thyroid hormone synthesis o Thionamides ▪ Propylthiouracil 400mg stat then 200mg Q6H ▪ Mechanism of action: competes with thyroglobulin tyrosine residues for thyroid peroxidase catalyzed iodination, thereby decreasing the numbers of mono and di-iodotyrosines ▪ PTU inhibits T4 to T3 conversion in both the thyroid and peripheral tissues Prevent thyroid hormone release o Lugol’s iodine ▪ Wolff Chaikoff effect is an autoregulatory phenomenon whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis within the follicular cells ▪ Must be administered at least 1H after 1st dose of PTU to prevent iodine from being utilized as a substrate for synthesis Decrease peripheral action of circulating thyroid hormone and support the circulation o Corticosteroids 14 16 Aug 2024  SIT Internal ▪ Inhibit peripheral conversion of T4 to T3 ▪ Treats concomitant/relative adrenal insufficiency o Beta-blockers 3. Treat the precipitant 15 16 Aug 2024  SIT Internal Primary Hypothyroidism Characterised by the deficient production of thyroid hormones due to an intrinsic dysfunction of the thyroid gland itself Causes o Previous surgery o Radioiodine therapy o Previous radiation to the neck o Drugs o Hashimoto’s thyroiditis Clinical presentation o Fatigue o Weight gain o Cold intolerance o Constipation o Bradycardia Treatment o Levothyroxine replacement therapy ▪ Must be taken 60 minutes before a meal or 4 hours after the last meal ▪ Things that interfere with absorption: diet (meals, calcium, grapefruit juice), bile acid sequestrants (cholestyramine), oral bisphosphonates, PPI/H2 receptor antagonists, ferrous sulphate, calcium carbonate/citrate/acetate o Goal is to normalize TSH levels 16 16 Aug 2024  SIT Internal Myxedema Coma State of decompensated hypothyroidism, resulting in multi-system dysfunction, characterized by thermoregulatory, cardiac and neurologic manifestations Popoveniuc diagnostic scoring system for myxedema coma Management 1. Acute stabilization of the patient Ensure airway, breathing and circulation 2. Thyroid specific management Empirical cover for hypocortisolism with IV hydrocortisone IV levothyroxine loading dose of 200-400mcg to saturate the receptors followed by maintenance IV levothyroxine Switch to oral levothyroxine only when patient is more alert 3. Supportive treatment Passive warming Management of metabolic disturbances and complications 4. Treatment of the precipitant 17 16 Aug 2024