Signs and symptoms of endocrine organ diseases and metabolic disorders. (diseases of pancreas and thyroid gland) Lecture in internal medicine propaedeutics Eugenia Golubkina, assistant of professor Department of Internal Medicine Kharkiv state university named after V. N. Karazin INTRODUCTION Endocrine gland - a gland of the body that produces hormones and secretes them directly into the bloodstream. Hormone-a chemical substance secreted by an endocrine gland or group of endocrine cells that acts to control or regulate specific physiological processes, including growth, metabolism, and reproduction. The American Heritage® Science Dictionary Hypothalamus/pituitary Thyroid gland Parathyroid glands PANCREAS Location : in the retroperitoneal space of the upper part of the abdomen. Features: almost completely covered by the stomach and duodenum. Has lobe-like structure. http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/pancreas_biliary_tract/c hronic_pancreatitis.pdf FUNCTIONS OF THE PANCREAS Pancreas has two main functions: 1. Exocrine: the acini of the pancreas secrete pancreatic juice to complete the digestion of chyme in the duodenum. Pancreatic juice is a mixture of water, salts, bicarbonate, and many different digestive enzymes. 2. Endocrine: the endocrine cells form the Islets of Langerhans, consisting of B (ß) cells secreting insulin, A (α) cells secreting glucagon, D (δ) cells secreting somatostatin, and F cells secreting pancreatic polypeptide. These hormones are secreted into the portal circulation. INSULIN AND GLUCAGON MAIN FUNCTIONS OF INSULIN Insulin is a polypeptide hormone, composed of two chains (A and B), derived from proinsulin Activates + Inhibits - Glucose Ketogenesis uptake in muscles and adipose tissue Glycolysis Glycogen synthesis Protein synthesis Amino acid transport Gluconeogene sis Glycogenolysis Proteolysis https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcR_jf1lerjdCqUhJBhZ8R97nVT4czJ4I3LOAi7fouMPM0D-10AM6A BASAL AND POSTPRANDIAL LEVELS OF GLUCOSE http://www.rnceus.com/dmeds/images/secretion.jpg BASAL AND POSTPRANDIAL LEVELS OF INSULIN SECRETION http://www.rnceus.com/dmeds/images/secretion.jpg NORMAL AND PATHOLOGICAL VALUES OF BLOOD GLUCOSE Euglycaemia – a normal blood glucose concentration; 3.9-5.5 mmol/l (70-99 mg/dl) Hyperglycaemia – high blood glucose concentration; >5.5 mmol/l (>70 mg/dl) Hypoglycaemia – low blood glucose concentration; Starts with 3.3-3.9 mmol/l (60-70 mg/dl) http://www.idf.org/sites/default/files/Diabetes-in-Childhood-and-Adolescence-Guidelines.pdf HYPERGLYCAEMIC SYNDROME Symptom Polydipsia (“poly” – much, many; “dipsia”thirst ) Polyuria Characteristic features Pathogenesis Amount of fluid intake is Increased osmolality of over 2 liters per day. blood due to hyperglycaemia leads to cellular dehydratation and activation of thirst center Amount of excreted Due to polydipsia and urine is over 2,5-3 liters glucoseuria (osmotic per day diuresis) Increased appetite (hunger) Compensatory reaction to decrease prevalence of catabolic state Polyphagia CAUSES OF HYPERGLYCAEMIA  Diabetes mellitus type1  Diabetes mellitus type2  Another types of diabetes mellitus  Severe stress  Critical illness (ex. MI, stroke, trauma, infections)  Surgery  Drugs (corticosteroids, thiazide diuretics, epinephrine, etc.)  Diet with high amounts of carbohydrates HYPOGLYCAEMIC SYNDROME Autonomic symptoms Trembling Palpitations Neurological (neuroglycopenic) symptoms Drowsiness Discoordination of speech and movements Abnormal behavior, Irritability, anger General symptoms Headache Dizziness Sweating Weakness Anxiety Hunger Nausea Confusion Seizures Dyplopia CAUSES OF HYPOGLYCAEMIA  Inadequate insulinotherapy  Strenuous exercise  Starvation  Alcohol abuse  Diseases such as hypothyroidism, tumors (insulinoma) healthline.com WHAT IS DIABETES MELLITUS? Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes - greek for “siphon” or “fountain” for the characteristic frequent urination; Mellitus - latin for “sweet as honey” Diabetes Care Volume 38, Supplement 1, January 2015 http://www.diapedia.org/introduction-to-diabetes-mellitus/1104085113 RISK FACTORS FOR DIABETES  Physical inactivity  First-degree relative with diabetes  High-risk race/ethnicity  Women who delivered a baby >9 lb or were diagnosed with GDM  Atherosclerosis  Arterial Hypertension  Conditions associated with insulin resistance: severe obesity, acanthosis nigricans, PCOS (polycystic ovary syndrome)  CVD history 2015 American Diabetes Association (ADA) Diabetes Guidelines - modified CLASSIFICATION OF DIABETES MELLITUS 1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced diabetes Diabetes Care Volume 38, Supplement 1, January 2015 MAIN TYPES OF DIABETES MELLITUS Insulin acts as a key that lets the body’s cells take in glucose and use it as energy. Insulin acts as a key that lets the body’s cells take in glucose and use it as energy. Insulin acts as a key that lets the body’s cells take in glucose and use it as energy. Diabetes Care Volume 38, January 2015 Diabetes mellitus 1 type Autoimmune disease: Islet cell autoantibodies, insulitis, Association with other autoimmune diseases Absolute deficiency of the insulin Usually lean ( lypolysis) Diabetes mellitus 2 type No immune disturbance Insulin resistance Is related to obesity, decreased physical activity and unhealthy diets Partial (relative) insulin deficiency initially Often overweight ( lypogenesis) Younger (usually < 30 years of age) Always need lifelong insulin for survival Usually (but not always) older (usually > 30 years of age) usually do not require insulin (can control glycaemia with diet and exercise, or with oral medications, or with the addition of insulin) Variable; from slow (often insidious) to severe Onset is mostly acute; Ketoacidosis is common SOME FACTS ABOUT DIABETES  Without insulin, a person with type 1 diabetes will die.  People with type 2 diabetes mellitus can stay undiagnosed for many years unaware of the long term damage being caused by the disease.  Poorly controlled diabetes leads to serious complications and early death.  Gestational diabetes can result in birth complications that can affect both mother and child and increase the risk for developing type 2 diabetes later in life. Diabetes Care Volume 38, January 2015 MACROVASCULAR COMPLICATIONS OF DIABETES Macrovascular complications - affection of large vessels: Peripheral vascular Coronary artery Cerebrovascular disease disease disease https://anu4bindu.files.wordpress.com/2013/03/diabetes-complications.jpg?w=614 http://healthy-ojas.com/diabetes/heart-disease.html MICROVASCULAR COMPLICATIONS OF DIABETES Microvascular complications affection of small vessels:  Retinopathy- damaged blood vessels in retina, may cause blindness;  Nephropathy – may lead to kidney failure and death  Neuropathy – “Walking on pins and needles” https://anu4bindu.files.wordpress.com/2013/03/diabetes-complications.jpg?w=614 DIABETES MELLITUS: MAIN COMPLAINTS Classic triple P: Poliuria - increased urinary frequency ; Polydipsia – increased thirst; Polyphagia – increased hunger http://dhrcindia.com/diabetes_e_6.html DIABETES MELLITUS: COMPLAINTS Other complaints of patients with diabetes Skin itching http://www.planetayurveda.com/blog/naturalherbal-remedies-diabetes-ayurvedic-treatment/ DIABETES: INSPECTION Symptom Dry peeling (flaking) skin with trophic changes, ulcers Pathogenesis As a result of dehydratation and affection of small vessels Xanteplasma palpebrarum Furunculosis, mycosis Rubeosis (redness of forehead, cheeks) Disbalance of lipids Impaired immunological defense Dilatation of capillaries http://www.skinsight.com/adult/xanthelasmaPalpebrarum.htm http://www.slideshare.net/ChamplainDRCC/foot-care-training-presentation-dec-6-2012-on-final DIABETES: PALPATION Assessment of Dry skin with humidity of skin decreased turgor Assessment of pedal pulse Assessment of skin temperature Palpation of liver Pulse is diminished or absent Decreased temperature of lower extremities Hepatomegaly as a result of steatosis http://www.osceskills.com/e-learning/subjects/peripheral-vascular-examination/ ASSESSMENT OF PEDAL PULSE The dorsalis pedis pulse is felt on the dorsal surface of the foot, just lateral to the extensor hallucis longus tendon. The posterior tibial pulse is felt on the posterior surface of the medial malleolus, between it and the medial border of the calcaneal tendon. https://academic.amc.edu/martino/grossanatomy/site/Medical/CASES/Lower%20limb/POP_UPS/popliteal%20anspop_up4.htm ASSESSMENT OF SENSITIVITY Nylon monofilament test. There is a risk of ulcer formation if the patient is unable to feel the monofilament when it is pressed against the foot with just enough pressure to bend the filament. The patient is asked to say “yes” each time he or she feels the filament. Failure to feel the filament at four of 10 sites is 97 percent sensitive and 83 percent specific for identifying loss of protective sensation. http://www.aafp.org/afp/1998/0315/p1325.html DIAGNOSTICS OF DIABETES  Complaints (polyuria, polyphagia, polydipsia, weight loss, etc.)  Anamnesis vitae ( i.e. family history of diabetes)  Anamnesis morbi (abrupt or slow onset, etc.)  Objective examination (signs of dehydratation, ketoacidosis, etc.)  Fasting plasma glucose (FPG)  Oral glucose tolerance test (OGTT)  Random plasma glucose  Urine analysis  Glycated haemoglobin (HbA1c)  C-peptide  Islet-autoantibodies CRITERIA FOR DIABETES * Normal Prediabetes Diabetes Fasting plasma 3.8-5.5mmol/l 5.6-6.9mmol/L 7.0 mmol/L or 126 mg/dL glucose (FPG) or or 70-99 mg/dl 100-125 mg/dL Oral glucose tolerance test (OGTT) *HbA1c <7.8 mmol/L or <140 mg/dl <5.7% 7.8–11.0 mmol/L or 140-199 mg/dl 5.7–6.4% ≥11.1 mmol/L or >200mg/dl ≥6,5% Symptoms of diabetes plus random plasma glucose concentration ≥ 11.1 mmol/l (200 mg/dl). *In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing. DIAGNOSTIC TESTS FOR DIABETES Urine analysis – findings: Glucosuria – presence of glucose in urine; can be detected if level of blood glucose exceeds more than 10-12 mmol/l (diabetes mellitus, renal tubular dysfunction – glucose is not being reabsorbed in tubules) Ketonuria - presence of ketones in urine (in case of ketoacidosis); Ketoreview.com ADDITIONAL TESTS C-peptide is a peptide composed of 31 amino acids. It is released from the pancreatic beta-cells during cleavage of insulin from proinsulin. The reference range is 0.8-3.1 ng/mL or 0.26-1.03 nmol/L (SI). Is decreased in 1 type DM, increased in insulin resistance. Islet autoantibodies: presence of ICA (islet cell antibodies ), IAA (antibodies to insulin) and GADA (antibodies against the enzyme glutamic acid decarboxylase) can confirm 1type diabetes mellitus or LADA (Latent autoimmune diabetes in adults ) Davidson’s Principles and Practice of Medicine, 21th edition, p.800 EMERGENCY STATES IN DIABETES: KETOACIDOSIS Diabetic ketoacidosis (DKA) is a complex disordered metabolic state characterized by hyperglycaemia, acidosis, and ketonaemia. Precipitating factors:  Infection, stress;  Discontinuation of or inadequate insulin therapy;  Intercurrent illness (i.e. MI, cerebrovascular accident)  new-onset type 1 diabetes or discontinuation of insulin in established type 1 diabetes  In young patients with type 1 diabetes, psychological problems complicated by eating disorders https://www.bsped.org.uk/clinical/docs/DKAManagementOfDKAinAdultsMarch20101.pdf http://care.diabetesjournals.org/content/32/7/1335.full.pdf+html PATHOGENESIS OF KETOACIDOSIS  In diabetic ketoacidosis, the insulin level is inappropriately low, leading to hyperglycaemia and inappropriately high rates of lipolysis. This state is accompanied by an increase in counterregulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine).  The excess of free fatty acids is oxidized to ketoacids (acetone, 3-beta-hydroxybutyrate, and acetoacetate), which are the hallmark of DKA. Accumulation of large quantities of ketone bodies leads to subsequent metabolic acidosis.  Since lipolysis is easily inhibited at low levels of insulin, ketoacidosis only develops in the presence of severe insulin deficiency, and is therefore more common for type 1 diabetes. http://www.diapedia.org/acute-and-chronic-complications-ofdiabetes/71040851425/diabetic-ketoacidosis-and-hyperglycaemichyperosmolar-state EMERGENCY STATES IN DIABETES: HYPOGLYCAEMIA Hypoglycemia is defined by:  the development of autonomic or neuroglycopenic symptoms;  a low plasma glucose level (<4.0 mmol/L for patients treated with insulin or an insulin secretagogue);  symptoms responding to the administration of carbohydrate Endogenous insulin Glucagon Adrenaline Noradrenaline Growth hormone Cortisol 3,0 mmol/l 4,5 mmol/l 4,0 mmol/l 3,5 mmol/l Onset of hypoglycaemic symptoms Neuroglycopenia 2,5 mmol/l 2,0 mmol/l Severe neuroglycopenia 1,5 mmol/l Canadian Diabetes Association Clinical Practice Guidelines Expert Committee http://www.emconsulte.com/en/module/displayarticle/article/278561/iconosup /fig0005 EMERGENCY STATES IN DIABETES: HYPOGLYCAEMIA Precipitating factors:  Inappropriate dose of insulin  Impaired awareness of hypoglycemia  Autonomic neuropathy  Skipping meals  Strenuous exercise  Alcohol Impaired awareness of hypoglycaemia (IAH) is an acquired complication of insulin therapy, which affects people with type 1 and insulin-treated type 2 diabetes mellitus, whereby the ability to perceive the onset of hypoglycaemia becomes diminished or absent. http://www.ncbi.nlm.nih.gov/pubmed/21211739 Symptoms Early signs Onset of coma Diabetic ketoacidotic coma Weakness, vomiting, dry mouth, polyuria Slow Hypoglycaemic coma Hunger, trembling (tremor), sweating Rapid Features of precoma Breathing Skin Tongue Progressive loss of conciousness Kussmaul respiration Dry with decreased turgor Dry with Excitation coma normal sopor Wet with normal turgor Wet Tone of eyeballs Glycaemia, glucoseuria Ketonaemia, ketonuria Decreased High present Normal or increased Low absent EMERGENCY STATES IN DIABETES: HHS Hyperosmolar hyperglycaemic state (HHS) is caused by blood hyperosmolality and pronounced intracellular dehydration without ketosis and can be characterized by:  Hypovolaemia  Marked hyperglycaemia without significant hyperketonaemia or acidosis  High Osmolality Features: It usually affects elderly patients, many with previously undiagnosed type 2 diabetes. Hyperosmolar coma develops gradually over several days, rarely - overnight. The management of the hyperosmolar hyperglycaemic state (HHS) in adults with diabetes Joint British Diabetes Societies EMERGENCY STATES IN DIABETES: HHS Precipitating factors:  Severe dehydration - vomiting, diarrhea, blood loss, increased urine output, burns, frostbite;  Excessive injection of solutions of glucose and saline solutions;  Intercurrent infectious diseases;  Surgery;  Prolonged treatment with diuretics, massive doses of corticosteroids, immunosuppressants. The predecessors of HHS are: polyuria, polydipsia, sometimes polyphagia. Then develops fatigue, signs of dehydration, drowsiness, confusion. Blood hyperosmolality is accompanied by a pronounced tendency to thrombosis, severely impaired microcirculation in different tissues - especially in the brain and kidneys. THYROID GLAND Location and anatomy : The thyroid gland is made up of the isthmus and 2 lateral lobes. The isthmus overlies the 2nd and 3rd rings of the trachea whilst the lobes extend from either side of the thyroid cartilage downward. Macleod's Clinical Examination, 12th Edition Oxford Handbook of Clinical Examination and Practical Skills, 1st Edition FUNCTIONS OF THYROID GLAND The thyroid synthesizes two hormones, L-thyroxine (T4) and triiodothyronine (T3), of which T3 acts at the cellular level and T4 is the prohormone. Main functions of thyroid hormones are:  accelerated rate of utilization of foods for energy;  increased protein synthesis and the rate of protein catabolism;  increase the rate and depth of respiration;  increased heart rate and cardiac output;  increased bone turnover and resorption;  increases gut motility;  stimulation of erythrogenesis FUNCTIONS OF THYROID HORMONES CONT.  increased speed of muscle contraction and relaxation and muscle protein turnover.  increased hepatic gluconeogenesis/glycolysis and intestinal glucose absorption.  increased lipolysis and cholesterol synthesis and degradation  increased catecholamine sensitivity and β-adrenergic receptor numbers in heart, skeletal muscle, adipose cells and lymphocytes.  Decreases cardiac α-adrenergic receptors. HYPOTHALAMUS-PITUITARY-THYROID AXIS  TRH (synthesized by the hypothalamus) is transported to the pituitary gland, where it binds to receptors on thyrotrophic cells, stimulating the synthesis and secretion of TSH.  TSH is transported in the circulation to the thyroid gland, where it binds to the TSH receptor on thyrocytes. This stimulates iodide transport, organification,hydrolysis TRH - thyrotropin-releasing hormone ; of thyroglobulin, and secreTSH- thyroid-stimulating hormone tion of thyroid hormone.  Circulating T4 and T3 exert negative feedback at the levels of both the hypothalamus and the pituitary gland, inhibiting the synthesis and secretion of TRH and TSH, respectively. www.123rf.com FUNCTIONAL STATE OF THYROID GLAND Euthyreosis – normal levels of thyroid hormones T3 and T4 Hyperthyroidism – syndrome caused by persistently elevated level of thyroid hormones T3 and T4 in blood, which occurs with various diseases or excessive exogenous entry of thyroid hormones. Hypothyroidism - syndrome characterized by prolonged persistent lack of thyroid hormones in the body or reducing their effect at the tissue level. PATHOLOGICAL STATES OF THYROID GLAND Hyper- and hypothyroidism can be:  primary (lesions in thyroid gland) and  secondary or central (lesions in pituitary or hypothalamus). Euthyreosis TSH (0.4–4.2 mlU/L) Free T4 (10–25 pmol/L) Increased Low Free T3 (3.5– 7.5 pmol/L) Increased low Primary/Secondary Suppressed/Increased Hyperthyroidism (< 0.05 mU/L) Primary/Secondary Increased (> 10 hypothyroidism mU/L)/Normal CAUSES OF HYPERTHYROIDISM  Diffuse toxic goitre (Grave’s disease, Bazedow’s disease)  Nodular (multinodular) goitre  Thyroiditis (acute, subacute, etc.)  Solitary thyroid adenoma  Drugs (e.g. amiodarone, l-thyroxine)  Struma ovarii (ovarian teratoma containing thyroid tissue)  TSH-secreting pituitary adenoma Macleod's Clinical Examination, 12th Edition CAUSES OF HYPOTHYROIDISM Primary hypothyroidism:  Congenital absence of thyroid tissue  Autoimmune diseases and autoimmune thyroiditis (Hashimoto’s thyroiditis)  Surgical removal of thyroid tissue, radioablation of thyroid tissue by radioactive iodine or external beam radiation  Impaired thyroid hormone synthesis, iodine deficiency  Congenital enzymatic defects that disrupt thyroid hormone synthesis  Drug-mediated inhibition of thyroid hormone  production and release ( eg. amiodarone) Secondary hypothyroidism:  Insufficient secretion of TRH or TSH  Tumor (lymphoma, germinoma, glioma)  Hypopituitarism  Pituitary surgery and radiation https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcQ8KqUu6Ab-w-8Y6dfpB1ppJP8or9szDY9RgK3cXndffcmlqOmr3w SYNDROME OF HYPERTHYROIDISM : COMPLAINTS Symptom Weight loss (>10%) Weakness Sweatiness, increased temperature Irritability, fast mood changes Palpitations, intermissions in the work of the heart Diffuse neck swelling Pathogenesis thyroid hormones activation of metabolic processes Toxic myopathy baseline metabolism Toxic encephalopathy Sympaticotonia Presence of goitre (enlargement of thyroid gland) HYPERTHYROIDISM: INSPECTION, PALPATION Symptom Warm skin Hyperhydrosis Features Pathogenesis Increased Hypermetabolic state temperature of skin Wet palms, increased sweating Autonomic dysfunction and increased temperature Hyperplasia of folliculi, of thyroid gland autoimmune-mediated inflammatory process of the orbital tissues, predominantly affecting the fat and the extraocular muscles Enlargement of Due to WHO thyroid gland classification Eye symptoms Positive Shtelwag’s, Moebius’s, Gref’s, Dalrymple symptoms WHO CLASSIFICATION OF GOITRE • Grade 0 - no palpable or visible goitre • Grade 1 - A goitre that is palpable but not visible when the neck is in the normal position (i.e., the thyroid is not visibly enlarged) • *thyroid nodules in a thyroid which is otherwise not enlarged fall into this category • Grade 2 - A swelling in the neck that is clearly visible when the neck is in a normal position and is consistent with an enlarged thyroid when the neck is palpated Macleod's Clinical Examination, 12th Edition http://apps.who.int/iris/bitstream/10665/43781/1/9789241595827_eng.pdf PALPATION OF THYROID GLAND Pay attention on:  Shape and surface (smooth, diffuse, symmetric or not);  Mobility (moves with swallowing or not);  Consistency (nodules);  Tenderness (diffuse or localized);  Thyroid bruit; Anterior approach Posterior approach www.studyblue.com HYPERTHYROIDISM : LESIONS OF SYSTEMS System Respiratory Cardio-vascular Lesion RR>18/min Tachycardia HR>100/min (palpitations) Arterial systolic hypertension Rhythm disturbances (Atrial fibrillation) Cardiac failure Diarrhoea Vomiting Irritability, tearfulness, behavior change Tremor Fatigue Restlessness Gastro-intestinal Nervous GRAVE’S DISEASE  Synonims: diffuse toxic goitre, Basedow's disease (Germany), Grave's disease (Britain), Flajani`s disease (Italy).  Definition: it is autoimmune thyroid disease, which manifests with diffuse thyroid enlargement and hyperthyroidism.  Cause of hyperthyroidism in Graves’ disease is the production of thyroid-stimulating immunoglobulins (autoantibodies) that bind to and activate the TSH receptor, promoting thyroid hormone secretion and growth of the thyroid gland (they behave like TSH). PATHOGENESIS OF GRAVE’S DISEASE http://img.medscapestatic.com/pi/meds/ckb/19/43419.jpg GRAVE’S OPHTHALMOPATHY Exophtalmos (proptosis) - abnormal protrusion of the eyeball Stellwag sign (stare)- incomplete and infrequent blinking Möbius sign - poor convergence Dalrymple sign - retraction of the upper and/or lower lid due to hyperstimulation of the sympathetically innervated muscles in the upper and lower lids; von Graefe sign (Lid lag on downgaze) - while slowly moving the fixation object from upward to downward, the eyelid lags behind the globe on downgaze. Seidel H: Mosby’s guide to physical examination, 4th ed 4, St. Louis, 1999, Mosby, Macleod's Clinical Examination, 12th Edition THYROID DERMOPATHY Synonyms: pretibial myxedema (PTM), localized myxedema  It can be described as localized lesions of the skin resulting from the deposition of hyaluronic acid in the dermis and subcutis.  The precise cause of PTM remains uncertain but it is nearly always associated with autoimmune thyroid disease  Although PTM is most often confined to the pretibial area, it may occur anywhere on the skin, especially the ankle, dorsum of the foot, knees, shoulders, elbows, upper back, pinnae, nose, neck. Thyroid dermopathy. Courtesy of Dr. Vahab Fatourechi, Mayo Clinic THYROID STORM Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones in individuals with thyrotoxicosis. Predisposing factors:  Sepsis,  Surgery, anesthesia induction  Radioactive iodine (RAI) therapy  Drugs (anticholinergic and adrenergic drugs, eg, pseudoephedrine; salicylates; NSAIDs; chemotherapy)  Excessive thyroid hormone (TH) ingestion  Withdrawal of or noncompliance with antithyroid medications  Direct trauma to the thyroid gland  Vigorous palpation of an enlarged thyroid http://emedicine.medscape.com/article/925147-overview#showall THYROID STORM: CLINICAL PRESENTATION  Fever (38.5°C - 41°C)  Excessive sweating  CVS: accelerated tachycardia, hypertension with wide pulse pressure, high-output cardiac failure, cardiac arrhythmias (supraventricular arrhythmias are more common, [eg, atrial flutter and fibrillation], but ventricular tachycardia may also occur).  NS: severe agitation, altered behavior, delirium, seizures, and coma.  GIT: diarrhea, vomiting, jaundice, and abdominal pain. http://4.bp.blogspot.com/-_hdyQkhLmpk/UUAGP3lINEI/AAAAAAAACVg/2HjkoG9YJiY/s1600/fever-thermometer.jpg GRAVE’S DISEASE: INVESTIGATIONS Thyroid function tests:  Thyroid hormones - T3, T4 NB! In most patients serum T3 and T4 are both elevated but T4 is in the upper part of the normal range and T3 raised (T3 toxicosis) in about 5%.  TSH NB! Serum TSH is undetectable in primary thyrotoxicosis but values can be raised in the very rare syndrome of secondary thyrotoxicosis caused by a TSH-producing pituitary adenoma. Antithyroid antibodies:  TSH receptor IgG antibodies (TRAb);  TPO (thyroid peroxidase) antibodies;  Thyroglobulin antibodies; These antibodies are elevated in most patients with Grave’s disease. GRAVE’S DISEASE: INVESTIGATIONS  Radioactive iodine scanning and measurements of iodine uptake NB! In Graves disease, the radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland. Iodine-123 thyroid scan  Ultrasound of thyroid gland with color-Doppler evaluation A Grey-scale image with increased echogenicity Color flow Doppler image with increased vascularisation http://image.slidesharecdn.com/thyroid-140315071819-phpapp01/95/thyroid-ultrasound-17-638.jpg?cb=1394898622 http://emedicine.medscape.com/ article/383062-overview GRAVE’S DISEASE: INVESTIGATIONS  Computed tomography scanning or magnetic resonance imaging (of the orbits) may be necessary in the evaluation of proptosis. If routinely performed, most patients have evidence of orbitopathy, such as an increased volume of extraocular muscles and/or retrobulbar connective tissue.  Biopsy rarely to exclude other reasons for hyperthyroidism (eg. cancer) Also can be done:  A CBC count to check for development of fever or symptoms of infection and hematological side effects of antithyroid medications;  Liver function test results should be obtained to monitor for liver toxicity caused by antithyroid medications. SYNDROME OF HYPOTHYROIDISM : COMPLAINTS Symptom Weight gain (>10%) Chilliness, cold intolerance, decreased temperature Pathogenesis thyroid hormones metabolic processes baseline metabolism inhibition of Constipation Facial puffiness Dysmenorrhoea Poor memory Diffuse neck Swelling motility of GIT The deposition of mucopolysaccharides in the subcutaneous fat tissue Dyshormonal encephalopathy Presence of goitre - goitrous hypothyroidism may occur in endemic goiter in iodine deficiency regions HYPOTHYROIDISM: INSPECTION, PALPATION Symptom Features Pathogenesis  Hypometabolic state: metabolism of proteins, lipids, carbohydrates, vitamins;  Autonomic dysfunction The deposition of mucopolysaccharides in the subcutaneous fat Edema of tongue, swelling of vocal cords Dry skin, decreased hyperkeratosis, temperature of dry brittle skin unmanageable hair, brittle nails Edemas, periorbital edemas Hoarse voice, enlarged tongue Non-pitting edemas HYPOTHYROIDISM : LESIONS OF SYSTEMS System Cardiovascular Lesion Bradycardia HR<60/min, hypotension, ischemic coronary disease due to atherosclerosis (hyperlipidemia) Decreased appetite, flatulence, constipation Sleepiness, poor memory, dementia, depression Gastrointestinal Nervous Congenital hypothyroidism may lead to cretinism (mental retardation) https://www.mja.com.au/sites/default/files/issues/180_04_160204/top10414_fm-3.jpg MYXEDEMA COMA  Mixedema coma a rare, life-threatening condition, occurs late in the progression of hypothyroidism. The condition is seen typically in elderly women and is often precipitated by infection, medication, environmental exposure, or other metabolic-related stresses.  Its characteristics include coma with extreme hypothermia (temperature 24° to 32.2 °C), areflexia, respiratory depression with CO2 retention, convulsions are not uncommon and cerebrospinal fluid (CSF) pressure and protein content are raised. HYPOTHYROIDISM: INVESTIGATIONS  Elevated TSH with decreased T4  Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 is considered mild or subclinical hypothyroidism  Assays for anti–thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies may be helpful in determining the etiology of hypothyroidism or in predicting future hypothyroidism.  In patients with hypothalamic or pituitary dysfunction, TSH levels do not increase in appropriate relation to the low free T4 levels.  Ultrasonography of the neck and thyroid can be used to detect nodules and infiltrative disease.  The use of color flow Doppler scanning allows assessment of vascularity, which can help to distinguish thyroiditis (decreased flow) from Graves disease (increased flow). http://emedicine.medscape.com/article/122393-workup#c6 HYPOTHYROIDISM: INVESTIGATIONS Other abnormalities include the following:  anaemia, which is usually normochromic and normocytic in type but may be macrocytic (sometimes this is due to associated pernicious anaemia) or microcytic (in women, due to menorrhagia)  increased serum aspartate transferase levels, from muscle and/or liver  increased serum creatine kinase levels, with associated myopathy  hypercholesterolaemia and hypertriglyceridaemia  hyponatraemia due to an increase in ADH and impaired free water clearance. HYPOTHYROIDISM: SCREENING No universal screening recommendations exist for thyroid disease for adults. The American Thyroid Association recommends screening at age 35 years and every 5 years thereafter, with closer attention to patients who are at high risk, such as the following:  Pregnant women  Women older than 60 years  Patients with type 1 diabetes or other autoimmune disease  Patients with a history of neck irradiation http://emedicine.medscape.com/article/122393-workup#c7 Thank you for your attention!