Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Approach to common endocrine disorders Dr Amir Babiker MBBS, FRCPCH (UK), CCT (UK), Msc Endocrinology and Diabetes - Queen Mary University, London (UK) Consultant Paediatric Endocrinologist, KKUH and Assistant Professor, KSU (KSA) Growth and Puberty disorders IS SHE SHORT? SHORT STATURE • Standing height > 2SD below the mean (< 2.5 percentile) for gender and chronological age. • Investigation of children <-2SDS identifies pathology in 14% • Investigation of children <-3SDS identifies pathology in 58% • Compare the child’s height with that of a larger population of a similar background and mid-parental target height. Key points • Short stature is defined as standing height or recumbent length more than 2 standard deviations (SD) below the mean value for chronologic age. • Height (growth) velocity (cm/year) is another key auxological parameter in the assessment of a child for short stature. • Height of a child must always be defined in the context of genetic potential conferred by parental heights. • Short stature must not be confused with failure to thrive. Genetic factors are also important GROWTH VELOCITY • Most important aspect of growth evaluation • Change in standing Ht over: • Infants: 4 mo • Children: 6mo • Normal (cm/yr) • • • • 1y: 25 2y: 12 3y: 8 Then until puberty: 4-7 cm REGULATION OF POSTNATAL GROWTH • Infancy: – Nutrition – GH/IGF-I • Childhood: – GH/IGF-I – Thyroxine • Pubertal: – GH/IGF-I – Sex steroids SS CAUSES • Non-pathogenic – Constitutional Delay of Growth and Puberty – Familial short stature • Nutritional • Intra-Uterine Growth Restriction & Genetic disorders – Syndromic e.g Silver-Russell syndrome – Non-syndromic • Systemic disorders and medications related – Cardiovascular disease e.g. congenital heart disease – Renal e.g. chronic renal failure, RTA – Respiratory e.g. cystic fibrosis, asthma – Gastrointestinal disease e.g. IBD – Neurological e.g. brain tumour – Psychosocial e.g. anorexia nervosa, child abuse • Endocrine disorders CDGP VS FAMILIAL SS SS Causes: Endocrine causes GH-related causes • Growth hormone (GH) deficiency: isolated or combined with other pituitary hormone deficiencies • GH insensitivity Hypothyroidism Glucocorticoid excess • Cushing syndrome • Poorly managed congenital adrenal hyperplasia • Exogenous corticosteroid administration Pseudohypoparathyroidism IS SHE SHORT? EVALUATION OF SHORT STATURE Prenatal history, including maternal infection, consumption of alcohol or drugs, and smoking Pattern of growth (height and weight), including birth weight and length in relation to gestational age Family history, including parental heights and age of onset of puberty of parents and first-degree relatives Profile of patient’s pubertal development, including age of onset of breast development and menarche, testicular and penile enlargement, pubic hair, and body odor Nutrition Evaluation of short stature Evidence of systemic disease (gastrointestinal, cardiac, pulmonary, renal) Drug administration (steroids, methylphenidate) Psychosocial milieu Neurologic symptoms, especially headache, visual disturbance Physical Examination Accurate measurements of height, weight, head circumference, arm span, and upper and lower body segments Assessment of nutritional state and fat distribution Abnormal pigmentation of the skin Dysmorphic features Sexual maturity rating (Tanner staging) Neurological examination including fundoscopy and visual field tests Examination of the thyroid gland Target height of the child BOYS: [Father’s ht (cm)+ (mother’s Ht (cm)+ 13)] 2 GIRLS: [(Father’s ht (cm) -13) + mother’s Ht(cm)] 2 Inches: change 13 for 5’’ BASELINE INVESTIGATIONS FOR SHORT STATURE • Full blood count, ESR • Creatinine, urea, electrolytes • Calcium, phosphate, liver function tests • Ferritin, endomysial antibodies • Karyotype (in girls) • T4, TSH • Skeletal survey in dysmorphic children • Bone age X-ray (this is NOT a diagnostic investigation) Further investigations •Low levels of IGF-1 and IGFBP3 are suggestive of GH deficiency •Provocative GH stimulation test (insulin, arginine, clonidine, glucagon, L-dopa) is the accepted method for confirming the diagnosis of GH deficiency. FDA-Approved indications for growth hormone therapy • • • • • • • • • • GHD PWS SGA/IUGR Turner syndrome Noonan syndrome ISS Chronic renal insufficiency AIDS wasting Adult GHD SHOX deficiency Side effects of GH therapy •Hypothyroidism •Edema and sodium retention •Benign intracranial hypertension •Insulin resistance •Slipped capital femoral epiphysis •Scoliosis •Gynecomastia •???Development of cancers TALL STATURE: CAUSES ABNORMAL PUBERTY OVERVIEW • Physiology of normal puberty • Pubertal assessment • Early puberty: • Causes • Diagnosis • management • Delayed puberty: • Causes • Diagnosis • management TIMING OF PUBERTY INCOMPLETE PUBERTY • Premature thelarche • Premature Adrenarche • Premature menarche CAUSES OF CPP • Idiopathic (F>>M) • Organic CNS disruption: • Tumours of the hypothalamic-pituitary region • Post head injury / meningitis • Neurofibromatosis • Williams syndrome • Prematurity / Cerebral Palsy • Hydrocephalus • Post cranial surgery or radiotherapy • Hypothyroidism • Priming PRECOCIOUS PSEUDOPUBERTY IN FEMALES Isosexual (feminizing) conditions • • • • • McCune – Albright syndrome Autonomous ovarian cyst Ovarian tumors Feminizing adrenocortical tumor Exogenous estrogens Heterosexual (masculinizing) • • • • • Congenital adrenal hyperplasia Adrenal tumor Ovarian tumor Glucocorticoid receptor defect Exogenous androgens. PRECOCIOUS PSEUDOPUBERTY IN MALES Isosexual • • • • • • Congenital adrenal hyperplasia Adrenocortical tumor Leydig cell tumor Familial male precocious puberty HCG secreting tumor Teratoma Heterosexual • Feminizing adrenocortical tumor • Exogenous estrogens CAUSES OF PSEUDO-PRECOCIOUS PUBERTY Sex steroids from the adrenal: • Congenital adrenal hyperplasia • Adrenal tumour • Premature adrenarche (<8-9 yr) • Cushing’s Syndrome Sex steroids from the gonad: • Ovarian tumour, cysts • McCune-Albright Syndrome • Testotoxicosis • HCG – secreting (germ cell) tumours Exposure to exogenous steroids ASSESSMENT History, Family history Physical examination: •Cutaneous lesions e.g neurofibromatosis, McCune Albright syndrome • CNS examination - Fundi Auxology: Pubertal staging (Tanner) + size of testes Height, weight, MPH, growth velocity Bone age INVESTIGATIONS Endocrine tests: • Testosterone / oestradiol • LH / FSH • Adrenal androgens (DHEA-S, androstenedione) • 17 –OH progesterone ± synacthen test • β HCG • GnRH test (central or pseudo-precocious) Radiology: • Pelvic ultrasound • MRI hypothalamic – pituitary region DNA analysis: • For known genetic disorders (testotoxicosis, McCune Albright Syndrome) THE GOALS OF TREATMENT FOR CPP • Improvement of adult height • Prevention of social and psychological problems. Treatment of Pseudopuberty – by treating the cause (e.g adrenal tumour or CAH) DELAYED PUBERTY/PUBERTAL FAILURE 1. Central (Hypogonadotrophic Hypogonadism) Physiological central delay and true GnRH /gonadotrophin deficiency 2. Peripheral (Hypergonadotrophic Hypogonadism) Primary gonadal failure HYPOGONADOTROPHIC HYPOGONADISM Constitutional delay of puberty • Chronic illness / systemic disease • Malnutrition (including anorexia nervosa, Dieting, overexercise) • Hypothyroidism Impaired H-P axis: • Tumours H-P axis • Congenital: SOD, Genetic defects • Acquired : CNS Radiotherapy / trauma HYPERGONADOTROPHIC HYPOGONADISM: GIRLS • Gonadal dysgenesis / Turner’s syndrome • Autoimmune ovarian failure • Gonadal failure following chemotherapy or abdominal irradiation • Toxic damage (iron overload) • Intersex disorders including CAIS • PCO Hypergonadotrophic hypogonadism: Boys • Testicular damage: cryptoorchidism, orchidopexy torsion etc. • Bilateral anorchia • Syndromes: Noonans’s, P-W S, L-M-B-B S • Gonadal dysgenesis: Klinefelter’s syndrome, other XY aneuploidy, XO / XY • Gonadal failure following chemotherapy or testicular irradiation ASSESSMENT INVESTIGATIONS TREATMENT OF DELAY/FAILURE THYROID DISORDERS THYROID GLAND • Thyroid gland is composed of over a million cluster of follicles • Follicles are spherical & consists of epithelial cells surrounding a central mass (colloid) • Thyroglobulin is a storage room • Two main hormones: – Tetraiodothyronine (Thyroxin) = T4 – Triiodothyronine = T3 Production of Thyroid Hormones NIS (Na+/I- Sympoter) TPO t1/2 = 5-7d t1/2 = < 24 hrs Effects of thyroid hormones •Foetal brain & skeletal maturation • Increase in basal metabolic rate • Inotropic & chronotropic effects on heart • Increases sensitivity to catecholamines • Stimulates gut motility • Increase bone turnover • Increase in serum glucose • Decrease in serum cholesterol • Conversion of carotene to vitamin A • Play role in thermal regulation Thyroid disorders: Aetiology • Congenital • Acquired – Primary – Secondary – Tertiary Congenital hypothyroidism • Agenesis (No goiter) or dysgenesis (aplasia, hypoplasia, ectopic gland) are the commonest causes…..85% • Dyshormonogenesis (10%) and a goiter will be present. Pendred syndrome with sensorineural deafness is the commonest (often euthyroid). • Transplacental maternal TSH receptor blocking Abs (TRBAb) account for 5% of cases. • Pituitary failure and maternal ingestion of goitrogens are other causes Congenital hypothyroidism • One of the most common treatable causes of Mental retardation • CH Screening is the most cost effective program • Almost all affected Newborns have no S/S at birth • Congenital Anomalies increased by 10%(cardiac) • It is permanent in more than 90% of the cases • The earlier diagnosis the better IQ A. Delayed epiphyseal appearance B. epiphyseal dysgensis Signs of congenital hypothyroidism 31% prolonged jaundice • 23% umbilical hernia • 21% constipation • 21% macroglossia • 19% feeding problems • 16% hypotonia • 16% hoarse cry • 13% large posterior fontanelle • 10% dry skin • 5% hypothermia • 2% goiter • 40% delayed bone age • Management of congenital hypothyroidism • Documentation – Free T4, TSH • Thyroid scan, ultrasound (optional) • Treatment (normal size full term) – start L-thyroxin at 10-15 mcg/Kg daily – Monitor TSH every 2-3 months during first 2 years of life. Acquired hypothyroidism • More common than hyperthyroidism • 99% is primary (< 1% due to TSH deficiency) • Hashimoto’s – most common thyroid problem (4% of population) – most common cause in iodine-replete areas – chronic lymphocytic thyroiditis – Associated with TPO antibodies (90%), less commonly Tg antibodies • Iatrogenic Hypothyroidism from radioactive iodine therapy Symptoms Symptoms – General Slowing Down – Lethargy/somnolence – Depression – Modest Weight Gain – Cold Intolerance – Hoarseness – Dry skin – Constipation (↓ peristaltic activity) – General Aches/Pains – Arthralgias or myalgias (worsened by cold temps) – Brittle Hair – Menstrual irregularities – Excessive bleeding – Failure of ovulation – ↓ Libido Examination • Dry, pale, course skin with yellowish tinge • Periorbital edema • Puffy face and extremities • Sinus Bradycardia • Diastolic HTN • ↓ Body temperature • Delayed relaxation of reflexes • Megacolon (↓ peristaltic activity) • Pericardial/ pleural effusions • Congestive heart failure • Non-pitting edema • Hoarse voice • Myopathy Diagnosis Congenital hypothyroidism • Thyroid hormone level • TSH • Thyroid scan • Maternal investigations: TFT and Abs Acquired Hypothyroidism • TSH • fT4 • Thyroid antibodies • Thyroid ultrasound • TSH: low in secondary hypothyroidism -high in primary hypothyroidism • TRH test: to differentiate between secondary & Tertiary hypothyroidism Hyperthyroidism (Thyrotoxicosis) Definition • Excessive secretion of T3 & T4 • Affects metabolic processes in all body organs • Hyperthyroidism is 4-10 times more prevalent in women Graves’ Disease • • • • Most common cause of hyperthyroidism Goiter, proptosis TSH-R antibody (stimulating) = TRAB 40-70% relapse after 2 years of treatment HYPERTHYROIDISM S&S Heat intolerance Hyperactivity, irritability Weight loss (normal to increased appetite) Diarrhea Tremor, Palpitations Diaphoresis (sweating) Lid retraction & Lid Lag (thyroid stare) Proptosis Menstrual irregularity Goiter Tachycardia A 15 years old female with classic Graves disease DIAGNOSIS • TSH level usually < 0.05 µu / ml • 95 % of cases, high FT4 & FT3 • In 5% high FT3 with normal T4 (T3 Thyrotoxicosis) • Thyroid receptor (TRAB) are usually elevated at diagnosis • Antibodies against thyroglobulin, peroxidase or both are present in the majority of patients TREATMENT Medical: • Beta-blockers • Carbimazole or Methimazole • PTU (propylthiouracil) Other modalities (definitive treatment) • Radioactive iodine • surgery ADRENAL DISORDERS BASIC ANATOMY OF THE HUMAN ADRENAL GLAND Length: 4 – 6 cm; Width: 2 – 3 cm. Weight : 3 – 5 g each VASCULAR SUPPLY OF THE ADRENAL One of the most vascular tissues Arterial supply: Superior, Middle and Inferior adrenal arteries Venous drainage: › Right adrenal vein Inferior Vena cava › Left adrenal vein Left Renal Vein Lymphatic drainage: Para-aortic lymph nodes Without cortisol, we could not live Cortisol functions: • help the body respond to stress • helps maintain blood pressure and cardiovascular function • helps slow the immune system's inflammatory response • helps balance the effects of insulin in breaking down sugar for energy • helps regulate the metabolism of proteins, carbohydrates, and fats • helps maintain proper arousal and sense of well-being • Pituitary gland, (at base of brain) makes ACTH that drives the adrenal gland • production of glucocorticoids ADRENAL DYSFUNCTION Decrease function Increase function • Adrenal insufficiency • Low cortisol, aldestrone • Low Androgens Eg Addison disease • Cushing syndrome High Cortisol • Hyperaldosteronism High aldosterone • Pheochromocytoma High catecholamine . ADRENAL INSUFFICIENCY • Primary or secondary • Congenital or Acquired (for each) • Symptoms • • • • • • • • Weight loss Anorexia Weakness Fever Depression Nausea / abdo pain Myalgia Confusion MANAGEMENT • Resuscitation • IV fluids (0.9% Nacl) • IV hydrocortisone • Continue with sick day rules AMBIGUOUS GENETALIA CUSHING SYNDROME CALCIUM METABOLISM AND ITS DISORDERS OUTLINES • Calcium metabolism • Calcium disorders (↓Ca, ↑Ca) • Parathyroid disorders • Vitamin D disorders • Rickets BONES CELLS PHYSIOLOGICAL IMPORTANCE OF CALCIUM • Calcium salts in bone provide structural integrity of the skeleton • Calcium ions in extracellular and cellular fluids is essential to normal function of a host of biochemical processes • • • • Neuoromuscular excitability Blood coagulation Hormonal secretion Enzymatic regulation CALCIUM HOMEOSTASIS • While PTH and vitamin D act to increase plasma Ca++-- • Calcitonin causes a decrease in plasma Ca++. CALCIUM HOMEOSTASIS ANATOMY AND FEEDBACK INHIBITION CAUSES OF HYPOCALCEMIA Hypo parathyroid Postoperative Non parathyroid PTH Resistance Vitamin D deficiency Pseudohypoparathyroidism Idiopathic Malabsorption hypomagnesaemia Post radiation Liver disease Congenital Kidney disease Vitamin D resistance PSUEDOPSEUDOHYPOPARATHYROIDIS M Similar clinical features but normal biochemistry (PTH, Ca and PO4) RICKETS Reduced mineralization of bone matrix due to calcium deficiency. Commonest cause is Vit D3 deficiency: • Dietary lack of the vitamin • Insufficient ultraviolet skin exposure • Malabsorption of fats and fat-soluble vitamins- A, D, E, & K. • Abnormal metabolism of vitamin D • Chronic renal failure. TYPES OF RICKETS • Nutritional • Vitamin D deficient • Vitamin D dependant type I • Vitamin D dependant type II (Vit D resistant) • Hypophosphataemic OTHER CONDITIONS THAT CAN CAUSE RICKETS • • • • • • • Medications Antacids Anticonvulsants Corticosteroids Loop diuretics Malignancy Prematurity CLINICAL FEATURES Skeletal deformities Features of hypocalcaemia ( eg. Apathetic, poor feeding, tetany and seizures) Hypotonia and delayed motor development INVESTIGATIONS Bone profile • calcium • Phosphate • Alkaline phosphatase • Parathyroid hormone • Vitamin D (25 OH VitD +/- 1,25 (OH)2 Vit D) • Urinary calcium and phospherus X- rays TREATMENT • Vitamin D supplement or • Vitamin D analogues (one alpha, calcitriol) Dose and type depends on the underline cause of Rickets • Calcium • Phosphate THE EFFECT OF TREATMENT Before After THANK YOU