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Endocrinology • Introduction • Dynamic function tests • Hypothalamus and pituitary function tests • Adrenal function • Thyroid function tests • Other glands. Thyroid gland • • • • • • Physiology of the thyroid gland. T3 and T4. Control of the thyroid gland. Tests for thyroid function. Hypothyroidism. Hyperthyroidism. Case 1 • Investigations of 63-year-old woman with effort angina revealed a serum TSH of 96 mU/L and a serum free T4 of 3.7 pmol/L. An ECG showed some evidence of ischemia but was not diagnostic of myocardial infarction. Further biological investigations revealed: Cholesterol 360 mmol/L less than 190 Creatinine kinase 290 U/L less than 150 AST 35 U/L 12-48 1. How would theses results interpreted? 2. What is the importance of knowing about myocardial ischemia? Thyroid gland • The thyroid gland is found in front of the trachea. • The thyroid gland secretes three hormones: thyroxin (T4) and triiodothyronine (T3), both of which are iodinated derivatives of the amino acid tyrosine, and calcitonine. • T4 is ten time more than T3, most T3 (approximately 80%) being derived from T4 by deiodination in peripheral tissues, particularly the liver, kidneys and muscle. • T3 is more potent than T4. Iodide Control Of thyroid hormone • The thyroid gland is under the control of the pituitary gland. • When the level of thyroid hormones (T3 & T4) drops too low, the pituitary gland produces Thyroid Stimulating Hormone (TSH) which stimulates the thyroid gland to produce more hormones. • Under the influence of TSH, the thyroid will manufacture and secrete T3 and T4 thereby raising their blood levels. The pituitary senses this and responds by decreasing its TSH production. • The pituitary gland is regulated by the hypothalamus. The hypothalamus produces TSH Releasing Hormone (TRH) which stimulates the pituitary gland to releaseTSH • Condition that increase ATP demand (cold environment, pregnancy, hypoglycemia) increase the secretion of thyroid hormones. 1. Thyroid hormones increase basal metabolic rate by stimulating the use of cellular oxygen to produce ATP, thus increase cellular metabolism of carbohydrate, lipids and protein. 2. Stimulate the synthesis of additional Na+/K+ ATPase which use large amount of ATP, more heat is given off and lead to increase body temperature (calorigenic effect) thus thyroid gland play major rule in maintenance of normal body temperature. 3. Stimulate protein synthesis and increase the use of glucose and fatty acid for ATP production, they also increase lipolysis and enhance cholesterol excretion thus reducing cholesterol level. 4. Enhance some action of the catecholamine (EP, NE) because they upregulate β receptors for this reason symptoms of hyperthyroidism include increase heart rate and increased blood pressure. 5. With growth hormone and insulin, thyroid hormone accelerates body growth (nervous and skeletal system), deficiency of thyroid hormone during fetal development or childhood causes severe mental retardation. Test Of thyroid function 1. Total thyroxin and triiodothyronine Measurement of plasma tT4 and tT3 concentration. Major disadvantage in that it is dependent on binding protein concentration (TBG) as well as thyroid activity (increase tT3 and tT4 compatible with hyperthyroidism can occur with normal thyroid function if there is increase in binding protein concentration). 2. Free thyroxin and triiodothyronine: • Various techniques have been developed which allow the estimation of fT4 and fT3 concentrations in plasma. • Naturally occurring antibodies to thyroid hormones are some times present in plasma and give high result, measurement of TSH solve the problem. 3. Thyroid-stimulating hormone (TSH) 4. TRH 5. Thyroid scan Isotope Scan Normal Abnormal Thyroid scan A dose of isotope is given and its distribution within the thyroid is determined using a gamma camera. This technique allows the identification of “hot, active” or “cold, inactive” nodules in a patient with lumps in the thyroid gland “malignant disease”. Hypothyroidism and Hyperthyroidism www.thyroid-disease.org.uk Hyperthyroidism Hypothyroidism Too much thyroid hormone Too little thyroid hormone Metabolism speeds up Metabolism slows down Hypothyroidism • Hypothyroidism: Underactive thyroid glands which leads to decrease in the thyroid hormone production. • Incidence in ♀ > ♂ by 3x. • Incidence increased with age (> 60 years). • Hypothyroidism usually develops slowly. • Types: – Primary Hypothyroidism (more common). – Secondary Hypothyroidism (uncommon, with other pituitary insufficiency symptoms). J. Dipiro, R. Talbert, et al. (2008), Causes of hypothyroidism • 90% of cases: – Autoimmune destruction of the thyroid gland (Hashimoto’s disease). – Radiation or surgical treatment of hyperthyroidism (Iatrogenic hypothyroidism). Causes of hypothyroidism • Rare cases: 1. Drugs induced: e.g. amiodarone. 2. TSH deficiency such in case of hypopituitarism. 3. Congenital defects such as blocks in the synthesis of T4 and T3 , end organ resistance to their action or even borne without a gland or with a part of gland (1:4000). 4. Severe iodine deficiency: daily requirement of Iodide is 75mcg which found in 10gm of ionized salt (one teaspoon). Clinical presentation of hypothyroidism 1. General: • Adults: varied & nonspecific symptoms (So need for lab analysis of TSH, T4 &T3 for confirmation). • Children (called Cretinism): failure to thrive. Clinical presentation of hypothyroidism 2. Symptoms: • Dry skin. • Cold intolerance (always feeling colder than others). • Weight gain (despite loss of appetite). • Constipation. • Weakness. • Lethargy. • Fatigue. Clinical presentation of hypothyroidism 3. Signs: • Coarse hair/dry skin. • Peri-orbital puffiness→ • Slow Relaxing Reflex. • Bradycardia. • Slow hoarse speech. Signs and symptoms of hypothyroidism Tiredness Puffy Eyes Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Inability to Concentrate Difficulty Swallowing Thinning Hair or Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Slower Heartbeat Menstrual Irregularities/ Heavy Period Infertility Cold Intolerance Constipation Elevated Cholesterol Muscle Weakness or Cramps Diagnosing hypothyroidism • Primary hypothyroidism: 1.↑ TSH. 2.↓ (Free ± Total T4 & T3). 3.Thyrotropin receptor antibodies (Hashimoto). • Secondary hypothyroidism: 1.Normal or ↓ TSH. 2.↓ (Free ± Total T4 & T3). Hyperthyroidism • Excess thyroid hormone from over-activity of thyroid gland, appeared with symptoms. • Causes of Hyperthyroidism: 1. Grave’s disease (most common). 2. Thyroiditis. 3. Drug induced: Iodine toxicity, Amiodarone and L-thyroxine overdose. 4. Pituitary-hypothalamus origin (adenomas). Clinical presentation of hyperthyroidism 1. Symptoms: • • • • • • • Nervousness. Anxiety. Palpitations Easy fatigability. Menstrual disturbances. Heat intolerance. Loss of weight despite increased appetite. 2. Signs: • Warm, smooth and moist skin. • Exophthalmos → • Unusually fine hair. • Separation of the end of the fingernails from the nail beds. 2. Signs: • Retraction of the eyelids and lagging of the upper lid behind the globe when the patient looks downward (Lid Lag)→ • Tachycardia at rest. • Rapid pulse. • Arrhythmia such as atrial fibrillation (specially in elders). Signs and symptoms of hyperthyroidism Nervousness Irritability Difficulty Sleeping Bulging Eyes/Unblinking Stare Hoarseness or Deepening of Voice Persistent Sore or Dry Throat Difficulty Swallowing Rapid or Irregular Heartbeat Infertility Menstrual Irregularities or Weight Loss Light Period Heat Intolerance Frequent Bowel Movements Warm, Moist Palms Excessive Vomiting in Pregnancy Increased Sweating First-Trimester Miscarriage Family History of Thyroid Disease or Diabetes Diagnosis of hyperthyroidism 1. Physical examination: • Enlargement thyroid gland. • Rapid pulse. • Look for moist and smooth skin. • Tremor of finger trips. • Fast relaxing reflex → Diagnosis of hyperthyroidism 2. Lab data: • ↓ TSH. • ↑ Free ± total T3 & T4. • Thyroid stimulating antibodies (Grave’s). • Thyroid biopsy. Diagnosis of hyperthyroidism 3. ↑ Radioactive Iodine Uptake (RAIU): • True Hyperthyroidism. • Thyroid gland actively overproducing T3 ± T4. 4. ↓ Radioactive Iodine Uptake (RAIU): • Indicate that high levels of thyroid hormone are not a consequence of thyroid gland hyperfunction but by thyroiditis or hormone ingestion (toxicity). Hyperthyroidism treatment • Non-pharmacological: – Surgery. • Pharmacological: – Anti-thyroid drugs. – Radioactive Iodine (RAI). Calcitonin • A thyroid hormone. • Produced by C-cells. • Physiological effects are opposite to those of PTH, lowers plasma Ca. • Rapid acting, short term regulator of plasma Ca levels. • Stimulates osteoblasts, inhibits osteoclasts which causes removal of Ca from plasma to calcify new bone. • Minor role in adult due to PTH feedback, major role in children due to the rapid nature of bone remodeling and its effect on osteoclastic activity. The End