Lecture 01 endocrinology (complete).pptx

Endocrinal diseases Lecture I By: Ahmed Rashad Mashaal Definition  Endocrine glands are ductless glands richly supplied by blood vessels.  they secrete hormones that act as chemical messengers.  Hormones may be transported in the bloo...

Endocrinal diseases Lecture I By: Ahmed Rashad Mashaal Definition  Endocrine glands are ductless glands richly supplied by blood vessels.  they secrete hormones that act as chemical messengers.  Hormones may be transported in the blood to a distant site of action or act directly upon nearby cells (paracrine activity). What is the endocrine system? A- The pituitary gland The pituitary gland lies in the base of the skull (hypophyseal fossa in sella turcica). Itis connected to the hypothalamus by the pituitary stalk. The pituitary gland is composed of anterior & posterior lobes. I- Introduction  The anterior lobe of your pituitary gland is made up of several different types of cells that produce and release different types of hormones, including: 1. Growth hormone. regulates growth and physical development. It increase protein anabolism, leading to increased growth of bones, muscles, cartilage and viscera. 2. Thyroid-stimulating hormone (TSH) activates thyroid gland to release thyroid hormones. they are crucial for metabolism. 3. Adrenocorticotropic hormone (ACTH) stimulates adrenal cortex to produce cortisol and other hormones. 4. Follicle-stimulating hormone (FSH): is involved with estrogen secretion and the growth of ova cells in women. It’s also important for sperm cell production in men. 5. Luteinizing hormone. is involved in the production of estrogen in women and testosterone in men. 6. Prolactin: stimulates production of milk. I- Introduction: Anterior lobe hormones  The posterior lobe hormones are usually produced in hypothalamus and stored in the posterior lobe until they’re released.  Vasopressin. This is also called antidiuretic hormone (ADH). It helps your body conserve water and prevent dehydration.  Oxytocin. This hormone stimulates contractions of the uterus during labor. It also stimulate the release of breast milk. I- Introduction: posterior lobe hormones Gigantism Dwarfism  Usually due to pituitary gland  Due to deficiency of GH in tumor (adenoma) during early childhood. childhood.  The patients usually have  Increased secretion of growth well proportioned dwarfism hormone before epiphyses of with childish facies & long bones have united. normal mental function.  The patients complains from  Associated hypogonadism cardiac enlargement & heart & hypoglycemia may be failure + high incidence of developing type II diabetes present.  Treatment by giving mellitus.  The majority dies in early or recombinent GH middle ages. subcutaneously. II- Growth hormone abnormalities (during Childhood) Cause There is increased secretion of growth hormone after the epiphysis has united. It is mostly due to pituitary adenoma. Clinical picture Patient usually has Ape-like faces: big skull with long face, enlargement of the ears, nose, lips and tongue. The mandible becomes enlarged much greater than the maxilla, so the lower gaw becomes very prominent (prognathism). The teeth becomes more spaced and the lower teeth project beyond the upper ones to a considerable extent. Any applied dentures will become progressively ill-fitting. III- Acromegaly The patients also have enlarged hands & feet. The internal organs also increase in size: hepatomegaly, splenomegaly & cardiomegaly. Pressure manifestationsby the enlarging tumor may result in headache & blurring of vision  may end in blindness. III- Acromegaly (cont.) Diagnosis: Skull X-ray, C.T. & MRI are important for accurate diagnosis of the pituitary tumor. Management: Surgical resection or skull irradiation on pituitary gland. III- Acromegaly (cont.) B- The thyroid gland  The adult thyroid gland contains two lobes that wrap along the right and left anterolateral aspects of the trachea midway between the thyroid cartilage and the suprasternal notch.  The right and left lobes are connected by an isthmus on the anterior aspect of the trachea just below the cricoid cartilage.  The adult thyroid gland weighs 15 to 20 g.  Thethyroid gland is attached to the thyroid cartilage and to the upper end of trachea and thus moves on swallowing. I- Introduction Thyroid hormone (thyroxin) is synthesized within the gland. Thyroxin has a stimulatory effect on the metabolic rate of nearly all the body cells. Actions of thyroid hormones 1. Increase tissue metabolism, heat production & oxygen consumption. 2. Stimulate skeletal growth & mental development. 3. Diabetogenic effect: increase glycogenolysis in the liver. 4. Vasodilatation. 5. Decrease serum cholesterol level. 6. Increase conversion of carotene into vitamin A in the liver. 7. Finally, thyroid hormones increase the body’s sensitivity to catecholamines (epinephrine and norepinephrine) from the adrenal medulla, this effect accelerates the heart rate, strengthens the heartbeat, and increases blood pressure. I- Introduction (cont.) Definition: Causes  It is a clinical state 1. Graves’ disease(primary resulting from exposure of thyrotoxicosis): body tissues to excess autoimmune disease affects levels of thyroid mainly females 30-50 years. hormones. 2. Toxic multinodular goiter. 3. Solitary toxic nodule (toxic adenoma). 4. Acute stage of thyroiditis. 5. Secondary to pituitary adenoma secreting TSH. II- Hyperthrodism (thyrotoxicosis)  Clinical picture 1  General: 1. Loss of weight in spite of increased appetite. 2. Intolerance to hot weather. 3. Excessive sweating & warm hands.  Thyroid gland: 1. Graves’ disease: diffuse mild enlargement & smooth. 2. Toxic nodular goiter: More enlarged (may be huge) & nodular.  Nervous system: 1. Irritability & nervousness. 2. Insomnia. 3. Muscle wasting, weakness & fatigue. 4. Tremors in hands, tongue & eye lids. II- Hyperthrodism (thyrotoxicosis)  Clinical picture 2  Eye: 1. Staring look. 2. Lid lag: upper eye lid lag behind the moving eye balls when the patient looks down. 3. A rim of sclera is seen between the upper eye lid and the cornea when the patient looks forwards. 4. Exophthalmos (protrusion of the eyeballs).  Cardiovascular system: 1. Tachycardia, palpitation. 2. Arrythmias (e.g. Atrial fibrillation). 3. Increased systolic pressure  increased pulse pressure (hyperdynamic circulation).  GIT: 1. Diarrhea.  Genital: 1. Amenorrhea. II- Hyperthrodism (thyrotoxicosis) Investigations Treatment Elevated thyroid hormones (T3 & 1. T4). 1. B-Blocker to control 2. Decreased TSH (due to negative heart rate. feedback effect on pituitary gland)  except in secondary causes. 2. Anti-thyroid drugs 3. Autoimmune markers in Graves’ (carbimazole): interfere disease: anti-thyroglobulin Ab. with thyroid hormone 4. Thyroid scan: to assess the size & shape of the gland and to synthesis. differentiate between Graves’s disease from multinodular goiter. 3. Radioactive iodine. 4. Surgery for patients with nodular goiter or huge goiter. II- Hyperthrodism (thyrotoxicosis)  Causes:  Primary 1. Autoimmune: Atrophic thyroiditis or Hashimoto’s thyroiditis. 2. Post surgical. 3. Post irradiation (or post radioactive iodine). 4. Tumor infiltration. 5. Defect in hormone synthesis (iodine deficiency).  Secondary: Hypopituitarism III- Myxoedema (hypothyrodism in adults)   Cariovascular system: Clinical picture 1. Bradycardia. 2. Hypertension  More common in females 3. Increased serum between 30-50 years. cholesterol  General: 4. Pericardial effusion. 1. Weight gain & slow  Nervous system: movement. 1. Slow mental function & 2. Cold intolerance. poor memory 3. Fatigue & weakness. 2. Depression. 4. The face is bloated with 3. Hoarse voice. puffy eyelids. 5. Lips & tongue are thick. 4. Peripheral neuropathy.  Skin:  GIT: 1. Cold, dry, coarse & thick skin 1. Constipation. (doesn’t pit on pressure).  Genital: 2. Hair is sparse & brittle. 1. Menorrhagia III- Myxoedema (hypothyrodism in adults)  Investigations Treatment 1. Thyroid hormones are low:  Replacement therapy decreased T3 & T4 levels. with L-thyroxin 2. Elevated TSH in primary thyroid diseases and lifelong. decreased in secondary  Start with small dose causes. (25-50 µg/day) and 3. Elevated serum cholesterol. increase gradually up 4. Anaemia: usually normocytic to 200 µg/day. normochromic anaemia. 5. Thyroid antibodies: are positive in autoimmune causes (Antithyroid peroxidase antibodies). III- Myxoedema (hypothyrodism in adults) There is a deficiency of thyroid hormones during infancy. Due to agenesis of the thyroid gland. Children will have stunted growth with mental retardation and slow pulse rate. Their faces show puffiness of the eye lids, depressed nasal bridge, big lips & large protruding tongue. There is delayed dentition & small teeth. Their skin is coarse, dry, pale and cold. IV- Cretinism C- The Parathyroid Glands They are normally four parathyroid glands which are situated posterior to the thyroid. The glands secrete parathyroid hormone (parathrmone hormone; PTH). PTH controls serum calcium & phosphorus in the blood. PTH has several actions all serving to increase plasma calcium: I- Introduction Actions of PTH: 1. Increase resorption of bone. 2. Increase intestinal absorption of calcium. 3. Increase renal reabsorption of calcium and increase renal excretion of phosphate. 4. Increase synthesis of vitamin D.  Normal serum calcium 8.5-10 mg/dl.  Normal serum phosphorus 2.5-4.5 mg/dl.  Calcium in the blood exists in 2 forms: 1- Ionised ca (50%): biologically active. 2-Non-ionised ca (50%): bound to serum albumin.  Acidosis increases ionised Ca, while alkalosis decreases it. I- Introduction  Etiology 1- Primary hyperparathyroidism: due to adenoma of the gland. 2- Secondary hyperparathyroidism: compensatory hyperplasia of the parathyroid glands due to prolonged hypocalcemia as in chronic renal disease. II- Hyperparathyroidism  Clinical picture:  Itmay be asymptomatic.  PTH enhances removal of  Hypercalcaemia & calcium calcium & phosphate from diuresis may lead to: bones which lead to: 1. Polyuria, polydipsia. 1. Bone pains & tenderness. 2. Renal stones. 2. Pathological fractures. 3. Nephrocalcinosis: 3. Osteitis fibrosa cystica calcification of renal tissue. (bone is decalcified with 4. Weakness & constipation. cyst formation). 5. Acute pancreatitis. 4. Jaws are decalcified but 6. Peptic ulcer. not the teeth. II- Hyperparathyroidism  Investigations:  High PTH levels.  Elevated serum calcium & low serum phosphate in primary causes.  Serum calcium may be normal & even decreased in secondary cases to chronic renal failure.  Typical features of bone disease in X-ray imaging: - Hands: subperiosteal erosions. - Skull: Pepper-pot skull. - Loss of lamina dura around the teeth. II- Hyperparathyroidism Etiology of hypoparathyroidism 1- Surgical removal of parathyroid glands during thyroidectomy. 2- Autoimmune disease. Hypoparathyroidism results in tetany. III- Hypoparathyroidism Definition of tetany: Causes of tetany  Increased excitability of 1-Renal failure (most the nerves due to important cause of reduction in the hypocalcemia). concentration of 2-Hypoparathyroidism. ionized calcium in the 3-Inadequate intake or plasma. absorption of calcium. 4-Alkalosis: the total serum calcium is normal, but the ionised portion is decreased. Causes: severe vomiting, excess intake of alkali and/or hyperventilation. IV- Tetany Clinical picture A) Manifest tetany 1-Muscle spasms:  Carpopedal spasm.  Trismus due to spasm of the facial & masseter muscles.  Laryngeal spasm.  Generalized convulsions. 2- Perioral & peripheral parasthesias. 3- Ectodermal changes:  Hypoplastic teeth.  Fall of hair.  Brittle nails. IV- Tetany Clinical picture B) Latent tetany Revealed only by tests 1-Chvostek’s sign:  A tap over the facial nerve before the ear causes twitching of the angle of the mouth & outer canthus of the eye 2- Trousseau’s sign:  Inflation of the Sphygmomanometer cuff above the systolic pressure for 3 minutes induces titanic contractions of the wrist & fingers. IV- Tetany Treatment A) Acute attack:  Calcium gluconate 10 ml(10%) very slowly I.V. to control convulsion. B) Long term therapy: Oral calcium gluconate supplementation + active form of vitamin D (alpha-calciferol). D- The Adrenal Glands  Adrenal glands are situated at the upper poles of the kidneys.  They are formed from outer cortex & an inner medulla. I- Introduction I- Introduction  Definition & causes: Clinical picture  It’s a clinical state resulting A- Disturbance in protein from exposure of the body metabolism: tissues to excess cortisol.  Muscles wasting & weakness.  More in females 30-40 years.  Bone: osteoporosis & pathological fractures.  Causes:  Skin: thin skin, poor healing of the 1) Adrenal adenoma or wounds, vascular purpura. carcinoma.  Red striae: due to rupture of the 2) Pituitary adenoma secreting subcutaneous collagen fibers excess ACTH. exposing the vascular Sc tissue. B- Disturbance in carbohydrate 3) Iatrogenic: prolonged therapy metabolism: with cortisone (corticosteroids) cushingoid  Hyperglycemia & may be syndrome. secondary diabetes. II- Cushing syndrome  Clinical picture (cont.) C- Disturbance in fat metabolism:  Moon face: rounded face with bloated checks.  Trunkal obesity: increased fat in obesity & abdominal wall.  Buffalo-hump: increase fat in the interscapular region. D- Disturbance in fluid & electrolytes:  Sodium retention leading to hypertension.  Loss of potassium in urine leading to hypokalemia & polyuria. E- Others:  Depression.  Polycythemia & plethoric faces.  Infection specially of the skin (bacterial & fungal). II- Cushing syndrome Investigations Treatment  CBC changes: Increase of  Surgical resection of the RBCs (polycythemia) + tumor followed by lifelong increase of neutrophils replacement therapy. (neutrophilia) +decrease of  Stop unnecessary long eosinophils. term treatment by  Elevation of serum cortisol steroids. level.  Medical therapies: new  Urinary free cortisol is drugs that inhibit steroid increased. synthesis.  CT & MRI of the pituitary & adrenal glands. II- Cushing syndrome Definition Causes  Failure of the adrenal gland to 1. Autoimmune disease produce the normal amounts of (80% of cases). glucocorticoids, mineralocorticoids and sex hormones. 2. TB, hemorrhage,  This condition results from metastasis destroying destruction of the entire adrenal the adrenal cortex. cortex. 3. Disease of hypothalamus or pituitary reducing the  Treatment of the condition production of ACTH. depends on lifelong replacement therapy (oral hydrocortisone + mineralocorticoid). Dose of cortisone is increased during stress, surgery or infection. III- Addison’s disease  Chronic adrenal failure Acute adrenal failure (Addison’s disease) (addisonian crisis)  Asthenia: muscle weakness,  Precipitating factor: stress, fatigue & weight loss. infection or surgery.  Sudden onset of severe  Abdominal pain, diarrhea, weakness, profound fatigue nausea & vomiting. & GIT disturbances (specially intractable  Hypotension & hypoglycemia. vomiting &diarrhea).  Dehydration.  Hyperpigmentation (due to the  Low blood presurre  increase of ACTH): areas exposed to the sun, scar, skin tachycardia  shock & renal creases, and mucus membranes shutdown.  If not urgently detected & as mouth & tongue. treated  death. III- Addison’s disease E- Insulin & Diabetes mellitus It is a peptide hormone consists of 51 amino acid. It is secreted by ẞ-cells of islets of langerhans. It is secreted in the inactive form (proinsulin) which splits into insulin & C- peptide.  Functions of insulin: A) Carbohydrates: hypoglycemic effect  Increase uptake and utilization of glucose by tissues.  Stimulates glycogenesis & inhibit glycogenolysis in the liver & muscles.  Inhibit gluconeogenesis in the liver. B) Fat metabolism:  Stimulates lipogenesis in adipose tissue & liver.  Inhibits lipolysis & ketogenesis. C) Protein metabolism: Anabolic. I-Insulin Definition:  Group of disorders characterized by chronic hyperglycemia due to relative insulin deficiency, insulin resistance or both.  Itaffects more than 120 million people worldwide.  Diabetes is usually irreversible and its late complications results in reduced life expectancy and major health cost. II- Diabetes mellitus  Type I Type II Insulin dependant diabetes mellitus Non-insulin dependant diabetes mellitus (IDDM) (NIDDM) There is insulin deficiency due to Most probably there is insulin damage of ẞ-cells. resistance. Insulin increases in early stages then decrease in later stages. It is probably an autoimmune There is a genetic predisposition disorder triggered by viral and is strongly related to obesity. infection Usually presents in young age It usually presents in adults ≥ 40 years Insulin is essential for therapy Oral antidiabetic drugs are usually effective & insulin therapy may be needed in late stages Ketosis is common Ketosis is less common II- Diabetes mellitus (types & classification) Clinical picture  May be asymptomatic & discovered accidentaly.  Polyuria.  Polydipsia.  polyphagia.  Symptoms of complications (e.g. Pruritis Vulvae/ parasthesia, tingling due to neuropathy).  In type I: Wight loss, may be dehydration and ketosis.  In type II: onset is gradual and the patient is obese. II- Diabetes mellitus  D) Cutaneous (skin) complications: Complications:  Pruritis, specially pruritis vulvae.  Skin infections: abscesses, furuncles and fungal infections. A) Renal complications:  Fat atrophy at site of insulin injection.  Recurrent urinary tract infection  may end in papillary necrosis. E) Neurological complications:  Diabetic nephropathy (diabetic  Peripheral neuropathy. glomerulosclerosis): proteinuria in early  Cranial nerve palsy: 3rd & 7th cranial stages, lately chronic renal failure. nerves. B) Eye complications:  Autonomic nervous system: impotence  Diabetic retinopathy  may end in retinal detachment. & postural hypotension.  Diabetic cataract.  Cerebral strokes.  Recurrent eye infection. F) GIT complications: C) Cardiovascular complications:  Oral: Dental caries, gingivitis &  Coronary heart disease: angina, loosening of the teeth. infarction and heart failure.  Stomach: gastroparesis (delayed  Cardiomyopathy. gastric emptying).  Atherosclerosis of the large vessels:  Liver: Non-alcoholic steatohepatitis may lead to cerebral stroke of lower limb ischemia & gangrene. (NASH/ fatty liver)  liver cirrhosis.  Intestine: Diarrhea (SIBO: small intestinal bacterial overgrowth). II- Diabetes mellitus Diagnosis Long term follow up  Fasting blood glucose ≥ 126  Glycated hemoglobin. mg/dl (normal 70-110 mg/dl).  Lipid profile.  Random  Serum creatinine. blood glucose ≥ 200 mg/dl.  Fundus examination.  Screen for microalbuminuria.  Oral glucose tolerance test (Two hours post prandial blood glucose): after 6 hours fasting, give the patient 75 gm glucose and test blood glucose 2 hours after; if ≥ 200 mg/dl is diagnostic (normally < 140). II- Diabetes Mellitus Treatment of Type I D.M.  Insulin therapy is the only available option.  There are 2 available regimens: A) Short acting insulin before each meal 3 times daily+ long acting insulin at bed time (more physiologic). B) Two daily doses of Maxitard (mix between short & intermidiate acting insulin) given before breakfast & dinner.  If ketosis is present, immediate hospitalization & treatment with I.V. insulin & I.V. fluids (saline) is mandatory. II- Diabetes Mellitus Treatment of type II D.M.  Diet: reduction of weight – regular exercise – strict simple sugar intake – better to consume complex carbohydrates in smaller amount – increasing fibers in diet reducing glucose absorption.  Oral antidiabetic agents.  Insulin therapy: may be used in advanced cases to achieve metabolic control. II- Diabetes Mellitus  Oral anti-diabetic 5. Dipeptidylpeptidase-4 agents: inhibitors:increases incretin level  decrease glucagon release  relative increase 1. Sulphonylurea: promote insulin levels, as Galvus®. release of insulin from pancreas, as Amryl®/ Diamicron®. 6. Alpha-glucosidase 2. Biguanides (metformin): inhibitors: inhibit intestinal increase anaerobic glycolysis, as absorption of glucose, as Cidophage® or Glucophage®. acarbose (Glucobay®). 3. Glitazones: insulin sensitizers (decrease insulin resistance) as actos ®. 4. Gliflozines (SGLT2 inhibitors): Injectable Glucagon like peptide1 receptor agonists (Victosa®): inhibits reabsorption of sodium Promote insulin secretion + inhibit & glucose in the nephrons, prandial glucagon secretion + causing glucosuria, as Forxiga decrease release of glucose from ®. the liver + decrease gastric emptying. Also used in decreasing body weight. II- Diabetes Mellitus  The metabolic syndrome is a combination of risk factors.  Overweight/ obesity is the corner block of the consequence of complications.  Obesity if not well controlled will result in insulin resistance, which in turn will end by diabetes mellitus with all associated complications.  According to the national cholesterol education program (NCEP) any 3 out of the 5 following features diagnose metabolic syndrome: 1. Waist circumference > 102 cm in men or 88 in women. 2. Serum triglycerides > 150 mg/dl. 3. HDL cholesterol (high density lipoprotein) < 40 mg/dl in males, and < 50 mg/dl in females. 4. Blood pressure ≥ 130/85 mmHg. 5. Fasting blood glucose ≥ 110 mg/dl.  These criteria will identify at-risk patients at earlier stages, this could lead to start therapeutic measures early.  Metabolic syndrome has become increasingly common worldwide.  People with the metabolic syndrome are at increased risk of hypertension, coronary heart disease, stroke, peripheral vascular disease, cancer and type II D.M. III- Metabolic syndrome  Clinical picture & Definition & causes treatment  Definition: blood glucose level is 1. Rapid onset of irritability, tremors below normal value (usually < 45 and pallor. mg/dl). 2. Lack of concentration & headache. 3. Sweating.  Causes: 4. Tachycardia & palpitations. 5. If hypoglycemia is prolonged: 1. Overdose of insulin or convulsions, brain damage and Sulphonylurea. death. 2. Insulin dosage with missed meal.  If the patient is conscious oral  Adrenaline is secreted to glucose or simple sugar could be increase glucose production in given. the liver.  If the patient in coma: IV glucose: 50 ml 50% glucose is given, followed by glucose 10% infusion until recovery. IV- Hypoglycemia Thank you