endocrinologydiabetes111.pptx

BY DR. K.K. ODINAKA ENDOCRINOLOGY • Endocrinology is the study of the biosynthesis, storage, chemistry, and physiological function of hormones with the cells of the endocrine glands and tissues that secrete them HORMONES • They are circulating messengers, with action at a distance from the orga...

BY DR. K.K. ODINAKA ENDOCRINOLOGY • Endocrinology is the study of the biosynthesis, storage, chemistry, and physiological function of hormones with the cells of the endocrine glands and tissues that secrete them HORMONES • They are circulating messengers, with action at a distance from the organ (gland) of origin of the hormone CLASSES OF HORMONES • Steroids – secreted primarily by the adrenal cortex, the gonads, the Kidneys e.g Cortisol, testosterone, oestrogen , Vitamin D, • Amines- secreted by the adrenal (epinephrine) and the thyroid (triiodothyronine [T3] and thyroxine [T4 medulla gland • Proteins /Polypeptides – peptide hormones include those released by the anterior and posterior pituitary, pancreatic islet cells, parathyroids, lungs (angiotensin II), heart and brain (atrial and brain natriuretic hormones), and hypothalamus (releasing hormones), as well as many local growth factors (insulin-like growth factor-1 FUNCTIONS OF THE ENDOCRINE SYSTEM • The endocrine system is important for • Regulation of growth (in utero and postnatal), • Pubertal development and reproduction • Energy production • Blood pressure • Behavior DISORDERS OF THE THYROID GLAND • The Thyroid gland consists of bilateral lobes extending from the side of the thyroid cartilage downwards to the 6th trachea ring, and the isthmus overlying the 2nd and 3rd rings of the trachea. • It develops from a bud which pushes out from the floor of the pharynx, and descends to its definitive position in the neck PHYSIOLOGY OF THYROID GLAND • The thyroid gland has 2 primary functions • 1. To secrete thyroid hormones [tyroxine ( T4) and triiodothyronine (T3)] • To secrete calcitonin which regulates the amount to circulating calcium NORMAL PHYSIOLOGY OF THE THYROID GLAND PHYSIOLOGY CONTD • Thyroid hormone secretion is regulated by the hypo-thalamic– pituitary axis. • Thyroid-stimulating hormone encourages thyroid cell growth and differentiation, increases iodine uptake , and stimulates the release of T3 and T4 (Thyroid hormones) • The release of TSH is stimulated by thyrotropin-releasing hormone (TRH) produced in the hypothalamus. • Increased circulating levels of thyroid hormone impose a negative feedback on TSH release as well as TRH. • T3 carries 3-4 times the metabolic potency of T4. Thyroid hormone synthesis absolutely requires iodine FUNCTIONS OF THYROID HORMONE CNS – • brain maturation, nerve function • Growth and development • Increases basal metabolic rate and heat production GIT – • Regulates metabolism of carbohydrates, proteins and fats • SKELETAL – Epiphyseal maturation HYPOTHYROIDISM • Hypothyroidism results from deficient production of thyroid hormone, either from a defect in the gland itself (primary hypothyroidism) or a result of reduced thyroid-stimulating hormone (TSH) stimulation. • The disorder may be manifested from birth (congenital) or acquired. CAUSES OF HYPOTHYROIDISM CONGENITAL HYPOTHYROIDISM • This is defined as thyroid hormone deficiency present at birth • Congenital hypothyroidism is the most common preventable cause of mental retardation. • Prevalence 1 in 4000 world wide. • Male : Female ….1:2 CONGENITAL HYPOTHYROIDISM • This is one of the commonest endocrine diseases of infancy. • Most cases of congenital hypothyroidism are not hereditary and result from thyroid dysgenesis. • Some cases are familial; these are usually caused by one of the inborn errors of thyroid hormone synthesis (dyshormonogenesis) and may be associated with a goiter. • Maternal medications …antithyroid medication in pregnancy CLINICAL FEATURES CLINICAL FEATURES • Most infants with congenital hypothyroidism are asymptomatic at birth, even if there is agenesis of the gland. This is because of transplacental passage of moderate amount of T4. • Birth weight and length are normal, but the head size may be slightly increased because of myxedema of the brain. SYMPTOMS AND SIGNS OF CONGENITAL HYPOTHYROIDISM • CNS : excessive sleep, hypotonia, hoarse cry, large open fontanelles, lethargy, coarse facies, increased head size, hearing loss, developmental delay, mental retardation* • DIGESTIVE SYSTEM: Constipation, poor appetite, protruberant abdomen, umbilical hernia, oedema of the genitals, • SKIN: cold and mottled skin, prolonged jaundice, myxedema of the skin, hypothermia SYMPTOMS AND SIGNS OF CONGENITAL HYPOTHYROIDISM • R/S : respiratory difficulties due to an enlarged tongue, include apneic episodes, noisy respirations • CVS: pulse is slow, heart murmurs, cardiomegaly, and asymptomatic pericardial effusion are common SYMPTOMS AND SIGNS OF CONGENITAL HYPOTHYROIDISM • MSS : Delayed growth, Delayed dentition and stunting • Haematologic : anaemia • Because symptoms appear gradually, the diagnosis is often delayed except with neonatal screening programme CLINICAL SCORING DIAGNOSIS • Serum TSH is elevated and T4 assay is decreased in primary hypothyroidism .Serum T3 may be normal, thus it is not helpful in the diagnosis • Roentenograph of skeletal will show retardation of osseous development at birth in 60% of affected newborns. The distal femoral epiphysis, normally present at birth, is often absent DIAGNOSIS • Ultrasonography of thyroid…. to locate the size and site • Electrocardiogram.. may show low voltage P and T wave with diminished amplitude of QRS complexes • Serum cholesterol : in children above 2 years of age cholesterol level is increased TREATMENT • Replacement therapy with sodium-L-thyroxine, orally for life is the treatment of choice • Thyroxine tablet should not be mixed with soy protein formula, iron OR Calcium because these can bind to T4 and limit its absorption. • Without treatment, affected infants become profoundly mentally deficient dwarfs. • Manifestations of excess therapy: craniosynostosis, temperament problems, pseudotumor cerebri ACQUIRED HYPOTHYROIDISM. • The symptoms appear after the first year of life, or in adolescents. It is twice more common in females than in males • Aetiology • Autoimmune ( hashimotor’s disease) • Iodine deficiency ( now rare) • Iatrogenic ( antithyroid drugs, irradiation, thyroidectomy) • Systemic disease ( Cystinosis, histiocytic infiltration} CLINICAL FEATURES • Deceleration of growth is usually the first clinical manifestation • Constipation, cold intolerance, • Delayed puberty in adolescents • Headaches and visual impairments. • NOTE: The disease does not affect school performance and mental ability even in severely hypothyroid children DIAGNOSIS: • Diagnostic studies are the same as those described for congenital hypothyroidism. • The presence of circulating thyroid antibodies implies an autoimmune basis for the disease. TREATMENT • L-thyroxine given as single daily oral dose for life. CASE PRESENTATION • A 4week old male was brought to the children out patient clinic with complaints of yellowish discoloration of the body of 2 weeks duration, protruding tongue, and constipation of 1 week duration • On examination, he was hypotonic, has umbilical hernia, OFC 30 cm. He also has a single transverse palmer crease on his right hand • QUESTION What is the most likely diagnosis? Mention 3 important investigations HYPERTHYROIDISM • This results from excessive secretion of thyroid hormones (T3 and T4) • Less common in children than in adult • In children, hyperthyroidism is almost always due to autoimmune over production of T3 and T4 (Graves’ disease). HYPERTHYROIDISM • Hyperthyroidism may also be due to • Acute, subacute, or chronic thyroiditis • Autonomous functioning thyroid nodules • Tumors producing TSH or TSH-like substances • McCune-Albright syndrome, • GRAVES DISEASE • Graves' disease is an autoimmune disorder in which TSH receptor antibodies bind to the TSH receptor, thereby resulting in the stimulation of thyroid hormone production and subsequent hyperthyroidism • It has a peak incidence in the 11-15 yr old age group; (In children, the disease most frequently occurs during adolescence) • It occurs in approximately 0.02% of children (1 : 5,000) • Hyperthyroidism is more common in female . (5 : 1 female : male ratio). . CLINICAL FEATURES • The earliest signs in children may be emotional disturbances. The children become irritable and excitable. They also cry easily because of emotional lability. They are restless sleepers and tend to kick their covers off • worsening school performance from short attention span, hyperactivity, emotional lability, nervousness, insomnia CLINICAL FEATURES • weight loss (despite increased appetite), • palpitations, • heat intolerance, increased perspiration • Diarrhoea • Hair loss DIAGNOSIS • Elevated serum levels of T3 and T4 with suppressed levels of TSH • The presence of TSH-receptor autoantibodies confirms the diagnosis of Graves' disease. (TSIs) • Imaging • In Graves disease, radioactive iodine uptake by the thyroid is increased, whereas in subacute and chronic thyroiditis it is decreased DIFFERENTIAL DIAGNOSIS • Hypermetabolic states (severe anemia, chronic infections, pheochromocytoma, and musclewasting disease) may resemble hyperthyroidism clinically but differ in thyroid function studies. TREATMENT • MEDICAL • B adrenergic agents: They can rapidly ameliorate the symptoms of hyperthyroidism (nervousness, tremor, and palpitations) B1 adrenegic blocking agents e.g Atenolol are preferred because they are cardioprotective. • Anti-thyroid drugs : Propylthiouracil(PTU) and metimazole (carbimazole). Metimazole is at least 10 times more potent than PTU and has a longer halflife(6-8hours) while PTU is preferred during pregnancy and for nursing mothers because PTU has a lesser ability to cross the placenta and to pass into breast milk. PTU use is not recommended in children due to its potential to cause liver failure • TREATMENT CONTD • RADIATION THERAPY • In radioactive iodine therapy, (I131) is administered orally and concentrates in the thyroid, resulting in ablation of the gland • SURGERY • This is indicated when medical therapy fails. Subtotal thyroidectomy THYROID STORM ( CRISES) • It is an acute, life-threatening hypermetabolic state caused by excessive release of thyroid hormones in individuals with hyperthyroidism • Clinical features: • Sudden onset • Fever • Profuse diaphoresis • Flushed warm skin • Tachycardia • Weakness, lethargy and confusion • Nausea, vomiting, diarrhea • Enlarge liver, jaundice • Coma THYROID STORM • It is fatal if left untreated. • It is extremely rare in children. Etiology 1.Sepsis 2.Surgery ( thyroid surgery) 3.Drugs e.g NSAIDS chemotherapy 4.Excessive thyroid hormone ingestion 5.Vigorous palpation of an enlarged thyroid gland Treatment Thyroid suppressive therapy Sympathetic blockade CASE SCENARIO • A 3 year old boy was brought to the Children outpatient clinic with complaints of Bulging eye balls of 4 weeks, excessive sweating and diarrhoea of 3 weeks , fever and weight loss of 2 weeks duration. • On examination his blood pressure was 180/110mmhg, he had periorbital ecchymosis and bluish subcutaneous nodules. • What is the most likely diagnosis? • Mention 2 important investigations necessary to confirm your diagnosis. DIABETES MELLITUS • IN CHILDREN LEARNING OBJECTIVES • At the end of the lecture, students should be able to • Discuss the pathophysiology of Diabetes Mellitus • Discuss the clinical features of diabetes • Discuss the treatment modalities for Diabetes Ketoacidosis CLINICAL VIGNETTE • A 6 year old boy was brought to the Emergency Paediatric Unit of IMSUTH with complaints of vomiting and abdominal pain of 5 days duration. He also complains of weakness, excessive thirst and hunger despite excessive intake of water and food. His genotype is AS. He is yet to achieve urinary continence at night. • On examination he had an asthenic build. He was lethargic , moderately dehydrated, mildly pale and no pedal oedema . He weighed 15 kilogrammes. • What is the LIKELY diagnosis? • Name 2 important investigations necessary to confirm your diagnosis. INTRODUCTION • The term diabetes mellitus describes a metabolic disorder characterized by hyperglycaemia resulting from defects in insulin secretion or insulin action • EPIDEMIOLOGY  Diabetes is the most common endocrine problem & is a major health hazard worldwide.  Incidence of diabetes is alarmingly increasing all over the globe.  Incidence of childhood diabetes range between 3-50/100,000 worldwide CLASSIFICATION • Type 1: Immune-mediated diabetes (previously called juvenile diabetes or insulin-dependent diabetes mellitus [IDDM]) is the most common type of diabetes in people younger than age 40 years. • It is associated with islet cell antibodies (immunologic markers), diminished insulin production, and being ketosis-prone CLASSIFICATION • Type 2 : (non–insulin-dependent diabetes mellitus [NIDDM], non–immune-mediated) is the most common type in persons older than age 40 years; it is associated with being overweight, insensitivity to insulin, and not being prone to ketosis. • Type 3: also known as ‘’Double diabetes” or atypical diabetes. This occurs where there is a coexistence of both types 1 and 2 diabetes. TYPE 1 DIABETES MELLITUS • The incidence and prevalence rates vary between countries, religion and race. • The prevalence is highest in FINLAND and lowest in Karachi (Parkistan). • Type 1 DM accounts for most cases of diabetes in childhood, however, it is not limited to this age group as new cases continue to occur in adult life TYPE 1 DIABETES MELLITUS • Peaks of presentation occur in 2 age groups: at 5-7 yr of age and at the time of puberty. The 1st peak may correspond to the time of increased exposure to infectious agents coincident with the beginning of school • The 2nd peak may correspond to the pubertal growth spurt induced by gonadal steroids and the increased pubertal growth hormone secretion (which antagonizes insulin). AETIOLOGY • The precise aetiology of DM is unknown, but it is regarded as a multifactorial disorder with Genetic, autoimmune and environmental components • GENETIC : The inheritance of HLA DR3 or DR4 confer a 2-3 fold increased risk of developing DM • Genetic syndromes associated with DM include Down syndrome, Klinefelter syndrome • Autoimmune : the presence of circulating islet cell antibodies in the serum of 85 % of newly diagnosed type 1 DM AETIOLOGY • ENNVIRONMENTAL FACTORS…. • Viral infections like Cytomegallovirus, mumps, Rubella • Drug or chemical induced e.g. Pentamidine, Diaxozide, Glucocorticoids, rodenticides (Vacor) • Dietary factors: Breastfeeding lowers the risk for DM PREDIABETES • It is used to identify individuals with abnormalities in blood glucose homeostasis who are at increased risk for the development of diabetes. • Prediabetes is defined by • Impaired fasting glucose (IFG, fasting glucose 100125 mg/dL [5.6-6.9 mmol/L]), • Impaired glucose tolerance (IGT, 2 hr postprandial glucose 140-199 mg/dL (7.8-11 mmol/L), • Hemoglobin A1c (HbA1c ) values of 5.7–6.4% • Prediabetes is not a clinical entity but rather a risk factor for future diabetes and cardiovascular disease PATHOPHYSIOLOGY • Insulin reduces blood glucose levels by allowing glucose to enter muscle cells and by stimulating the conversion of glucose to glycogen (glycogenesis) as a carbohydrate store. • Insulin also inhibits the release of stored glucose from liver glycogen (glycogenolysis) and slows the breakdown of fat to triglycerides, free fatty acids, and ketones. It also stimulates fat storage. PATHOPHYSIOLOGY • Additionally, insulin inhibits the breakdown of protein and fat for glucose production (gluconeogenesis) in both liver and kidneys PATHOPHYSIOLOGY CLINICAL PRESENTATION • Childhood type 1 diabetes can present in several different ways. • 1. Classic new onset. • 2. Diabetic ketoacidosis. • 3. Silent (asymptomatic) incidental discovery CLINICAL FEATURES • Classic new onset — Hyperglycemia without acidosis is the most common presentation of childhood type 1 diabetes. Symptoms are caused by hyperglycemia and include • Polyuria, nocturia, nocturnal enuresis • Polydipsia • polyphagia • Weight loss • In severe cases , the patient resents with DKA ( vomiting, abdominal pain, severe dehydration, acetone odor of breath and coma. DIAGNOSIS • Random blood sugar > (11.1mmol/l) 200mg/dl • Fasting blood sugar > 126 mg/dl ( 7 mmol/l) • Urinalysis ( presence of glucose and ketones on dip stick) DIAGNOSIS • Oral glucose tolerance test ( OGTT) is usually not necessary for diagnosis. • Other supportive laboratory investigations include : • Full blood count • S/E/U/Cr • Glycosylated haemoglobin TREATMENT • Initial management — The initial phase begins at the time of diagnosis. • In these first few days, the family begins to understand the disease process and is trained to successfully administer insulin, check blood glucose concentrations, check for ketonuria, recognize and treat hypoglycemia TREATMENT • Insulin ( preferably human insulin) is the main stay of treatment of type 1 DM. • Hyperglycaemia without severe acidosis or dehydration • Soluble insulin is given subcutaneously at a dose of 0.5-1units/kg /day 3 times daily . Insulin is given 30-60 minutes before meals 8hourly until patient is stable • After stabilizing the patient, the total dose is given twice daily using about 75% of the daily insulin dose as 2/3rd at breakfast and 1/3rd at dinner. Each dose is subdivided into 2/3rd intermediate acting and 1/3rd short acting preparations DIABETES KETOACIDOSIS • DKA is a paediatric emergency. • This condition is characterized by • Altered consciousness • Severe Dehydration • Blood glucose > 300mg/dl + glycosuria • Increased ketones in blood + ketonuria • Acidosis ( pH < 7.3, Hco3 <15meq/l DKA • Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus • The most common events that cause a person with diabetes to develop diabetic ketoacidosis are: • Infection such as diarrhea, vomiting, and/or high fever • missed or inadequate insulin and • Previously unknown diabetic patient SEVERITY OF DKA • The severity of DKA is categorized by the degree of acidosis • •Mild: venous pH7.25-7.35 or bicarbonate10-15 mmol/L • •Moderate: pH<7.15-7.25, bicarbonate 5-10 mmol/L • •Severe: pH<7.15, bicarbonate<5 mmol/l PRINCIPLES OF DKA MANAGEMENT • Fluid / Electrolyte management • Insulin therapy • Correction of acidosis • Treatment infection of underlying FLUID THERAPY • Rapid correction of shock and hypovolemia ( 1st hour) • Infuse 10-20mls/kg of normal saline or ringers lactate in the first one hour. • Slow correction of deficit +provision of maintenance ( over 24-36hours) • The infusion fluid is changed to 5% glucose IN 0.45% saline when the blood glucose falls to less than 250mg/dl (14mmol/l). INSULIN THERAPY •Insulin should only be given when shock has been successfully reversed. Regular insulin is the insulin of choice in DKA. •It should be given at a dose of 0.1units/kg/hour by intravenous infusion. •This causes a 50—100mg/dl/hr decline of blood glucose by •When the blood glucose falls to <250mg/dl(14mmol/l) the insulin dose can be reduced to 0.05u/kg/hr •When acidosis is corrected, insulin is changed from IV to subcutaneous at 0.2-0,4u/kg every 6-8 hours, given 30minutes before meals. ELECTROLYTE THERAPY Serum potassium may be normal , reducedor increased in DKA as a result of serum acidosis  With fluid , insulin and glucose therapy, acidosis is corrected and potasium moves back into the cells leading to hypokalaemia  The addition of potassium is started from the 2nd hour if urine has been passed.  CORRECTION OF ACIDOSIS/ TREATMENT OF INFECTION • Acidosis is corrected as the fluid volume is restored and insulin is administered to inhibit ketogenesis. • Bicarbonate infusion is given only in severe acidosis (pH < 7.1). Bicarbonate is given slowly and must be diluted because it may precipitate cardiac arrhythmias. • Treat any inter-current illness LONG TERM MANAGEMENT • Multidisciplinary- Paediatrician, Nurse, Dietician, Social worker, School teacher • The child and his family should assume responsibility for the daily diabetic care • They should be able to measure and record blood and urine glucose, recognize and treat hypoglycaemia, adjust insulin dosage in case of exercise and inter-current illness COMPLICATIONS • Hypoglycemia • KNIVES/ KEVINS….. • Kidney – nephropathy • Neuromuscular mononeuritis • Infective – UTIs, TB • • • – peripheral neuropathy, Vascular – coronary/cerebrovascular/peripheral artery disease Eye – cataracts, retinopathy Skin – lipohypertrophy/lipoatrophy, necrobiosis lipoidica • Other complications include : Psychosocial issues MONITORING • . Daily blood glucose at least 4 times; • - Before break fast • - Before lunch • - Before supper • - At bed time. • Initially test blood glucose also between 12AM & 3AM.to exclude nocturnal hypoglycemia MONITORING • Glycosylated hemoglobin (Hb A1c). • *Fraction of hemoglobin to which glucose has been attached. • * Measured as a percent of total hemoglobin. • *Value: Reflect average blood glucose over previous 2-3 months: • -Normal, non diabetic…………< 6% • - Good control --6 - 7.9 • -Fair control --+ 8-9.9 • - Poor control ~ > 1 0 TERMINOLOGIES • Honey moon period • About 75% of new diabetics complain recurrent hypoglycaemia which may recur for weeks to months. • This is due to residual B cell function ~ release insulin • Advice: never stop insulin but reduce the dose to avoid hypoglycaemia TERMINOLOGIES • The Somogyi phenomenon is rebound hyperglycemia after an incident of hypoglycemia. • The term dawn phenomenon describes a rise in blood glucose that occurs during the early morning hours (between 5:00 and 8:00 am), particularly among patients who have normal glucose levels throughout most of the night. CLINICAL VIGNETTE • A 5 month old boy was rushed to the Children emergency room with complaints of fever and vomiting of 5 days duration, passage of watery stool of 4 days duration , loss of consciousness of a day duration. He has not received any vaccination and mother bottle feeds him • On physical examination he was in respiratory distress, buccal mucosa was parched, radial pulse was barely palpable, blood pressure was 60/40mmhg. • What is the most likely diagnosis? • Mention 4 important investigations • How would you treat this patient ? CHOOSE THE BEST OPTION Blood sugar is well controlled when Hemoglobin A1C is: A. Below 7% B. Between 12%-15% C. Less than 180 mg/dL D. Between 90 and 130 mg/dL • 2. The risk factors for type 1 diabetes include all of the following except: a. Diet B Genetic c. Autoimmune d. Environmental CHOOSE TRUE OR FALSE • Diabetes mellitus in children: • A always presents with keto acidosis • B Can be managed with oral hypoglycaemic agents • C May be associated with prior mumps infection • D Has a peak incidence at 10-12 years of age • E. Px can present with Enuresis