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Dr Malith Kumarasinghe MBBS (Colombo) Hormones Transmit information between cells or organs Allow adjustment of internal and external environment Endocrine organs Synthesis and release hormones Maintain homeostatic mechanisms Endocrine Disorders Caused by abnormalities in hormone Synthesis Secretion Control Function Common Endocrine Disorders Diabetes mellitus Thyroid Disease Subfertility Menstrual disorders Osteoporosis Short Stature Delayed puberty Thyroid Disorders Surface Anatomy of Thyroid Where to look for Thyroid ? Background What: brownish-red, highly vascular gland Location: ant neck at C5-T1, overlays 2nd – 4th tracheal rings Avg width: 12-15 mm (each lobe) Avg height: 50-60 mm long Avg weight: 25-30 g in adults (slightly more in women) **enlarges during menstruation and pregnancy** Thyroid is made up of The isthmus The lateral lobes An inconstant pyramidal lobe projecting from isthmus Relations Anterior Pretracheal fascia Strap muscles Sternocleidomastoid Anterior jugular vein Posterior Larynx and Trachea Pharynx and oesophagus Carotid sheath Blood Supply Arterial Superior thyroid artery Inferior thyroid artery Thyroid ima artery Venous Superior thyroid vein Middle thyroid vein Inferior thyroid vein Innervation Principally from Autonomic Nervous system Parasympathetic fibers – from vagus Sympathetic fibers – from superior, middle, and inferior ganglia of the sympathetic trunk Enter the gland along with the blood vessels. Recurrent laryngeal nerve important structure lying between trachea and thyroid may be injured during thyroid surgery ipsilateral vocal cord paralysis, hoarse voice Questions Components of the thyroid gland? Relations of the thyroid gland? Physiology Produces hormones thyroxine (T4) and tri-iodothyronine (T3) are dependent on iodine and regulate basal metabolic rate calcitonin which has a role in regulating blood calcium levels THYROID HORMONES OH OH I I I I I O O NH2 I O Thyroxine (T4) OH NH2 I O OH 3,5,3’-Triiodothyronine (T3) Thyroid hormones – structure Thyroid hormones stored conjugated to thyroglobulin, but are cleaved by pinocytosis before being released into circulation Majority of the thyroid hormone secreted is T4 (90%), but T3 is the considerably more active hormone Although some T3 is also secreted, most is derived by deiodination of T4 in peripheral tissues, especially liver and kidney Both are poorly water soluble 99% of circulating thyroid hormone is bound to carrier protein (mostly thyroxine-binding globulin, but also transthyrein and albumin) Thyroid hormones – function Likely that all cells express thyroid hormone receptors Metabolism Increases basal metabolic rate Increases carbohydrate and lipid metabolism Normal growth Normal development Especially CNS Other systems CVS – increases heart rate, cardiac output CNS – mental acuity Reproduction – fertility requires normal thyroid function Thyroid regulation www.medscape.com; http://ae.medseek.com/ Thyroid pathology Normal thyroid function - ‘euthyroidism’ Disease states may result in hyper- or hypothyroidism - relative excess or deficiency of thyroid hormones Any swelling of the thyroid may be termed a goitre Toxic goitre: associated with increased thyroid hormone output Non-toxic goitre: normal hormone levels (Non-specific terms; don’t relate to a particular pathology) Epidemiology http://www.scielosp.org/scielo.php Hyperthyroidism Prevalence Women 2% Men 0.2% 15% of cases occur in patients older than 60 years of age Causes of Hyperthyroidism Graves Disease – Diffuse Toxic Goiter Plummer’s Disease Toxic phase of Sub Acute Thyroiditis Toxic Single Adenoma Pituitary Tumours – excess TSH Molar pregnancy & Choriocarcinoma (↑↑ βHCG) 7. Metastatic thyroid cancers (functioning) 8. Struma Ovarii (Dermoid and Ovarian tumours) 1. 2. 3. 4. 5. 6. Graves Disease The most common cause of thyrotoxicosis (5060%). Organ specific auto-immune disease The most important autoantibody is Thyroid Stimulating Immunoglobulin (TSI) TSI acts as proxy to TSH and stimulates T4 and T3 Toxic Multinodular Goiter (TMG) TMG is the next most common hyperthyroidism 20% More common in elderly individuals – long standing goiter Lumpy bumpy thyroid gland Milder manifestations (apathetic hyperthyroidism) Mild elevation of FT4 and FT3 Progresses slowly over time Clinically multiple firm nodules (called Plummer’s disease) Other causes….. Sub Acute Thyroiditis (SAT) Toxic Single Adenoma (TSA) Common Symptoms 1. 2. 3. 4. 5. 6. 7. 8. 9. Nervousness Anxiety Increased sweating Heat intolerance Tremor Hyperactivity Palpitations Weight loss despite increased appetite Reduction in menstrual flow or oligomenorrhea Common Signs 1. 2. 3. 4. 5. 6. 7. 8. Hyperactivity, Hyper kinesis Sinus tachycardia or atrial arrhythmia, AF, CHF Systolic hypertension, wide pulse pressure Warm, moist, soft and smooth skin- warm handshake Excessive perspiration, palmar erythema, Onycholysis Lid lag and stare (sympathetic over activity) Fine tremor of out stretched hands – format's sign Large muscle weakness, Diarrhea, Gynecomastia Thyroid Ophthalmopathy Proptosis Lid lag Onycholysis Thyroid storm Acute, severe, exacerbation of thyrotoxicosis due to acute serum T3/T4. Causes: stressors DKA, infection, acute I- tx withdrawal, trauma, thyroid gland manipulation, radioactive I-, surgery, ether anesthesia. Onset: sudden. For surgical pts at risk, it may occur: Intraop Postop: 6-18hrs. Signs T, HR, CHF, confusion, shock, death. Diagnosis 1. Typical clinical presentation 2. Markedly suppressed TSH (<0.05 µIU/mL) 3. Elevated FT4 and FT3 (Markedly in Graves) 4. Thyroid antibodies – by Elisa – anti-TPO, TSI 5. ECG to demonstrate cardiac manifestations 6. Nuclear Scintigraphy to differentiate the causes Treatment Options 1. Symptom relief medications 2. Anti Thyroid Drugs – ATD Methimazole, Carbimazole Propylthiouracil (PTU) 3. Radio Active Iodine treatment – RAI Rx. 4. Thyroidectomy – Subtotal or Total 5. NSAIDs and Corticosteroids – for Sub acute thyroditis Dietary Advice Avoid Iodized salt, Sea foods Excess amounts of iodide in some Expectorants, x-ray contrast dyes, Seaweed tablets, and health food supplements These should be avoided because the iodide interferes with or complicates the management of both ATD and RAI Rx. Hypothyroidism 1.8% of total population. Second only to DM as most common endocrine disorder. Incidence increases with age. More common in females. 2-3% of older women. Etiology PRIMARY HYPOTHYROIDISM Hoshimoto’s thyroiditis-most common Idiopathic hypothyroidism-probably old Hoshimoto’s Irradiation of thyroid Surgical removal Late stage invasive fibrous thyroiditis Iodine deficiency Drug therapy (Lithium, Interferon) SECONDARY HYPOTHYROIDISM 5% of cases. Pituitary or hypothalmic neoplasm. Congenital hypopituitarism. Pituitary necrosis (Sheehan’s syndrome) Thyroid Failure - Organ Systems Cardiovascular • Decreased ventricular contractility • Increased diastolic blood pressure • Decreased heart rate Central Nervous • Decreased concentration • General lack of interest • Depression Gastro-instestinal • Decreased GI motility • Constipation www.drsarma.in 48 Thyroid Failure - Organ Systems Musculoskeletal Muscle stiffness, cramps, pain, weakness, myalgia Slow muscle-stretch reflexes, muscle enlargement, atrophy Renal Fluid retention and oedema Decreased glomerular filtration www.drsarma.in 49 Thyroid Failure - Organ Systems Reproductive Arrest of pubertal development Reduced growth velocity Menorrhagia, Amenorrhea Anovulation, Infertility Hepatic Increased LDL / TC Elevated LDL + triglycerides www.drsarma.in 50 Thyroid Failure - Organ Systems Skin and Hair Thickening and dryness of skin Dry, coarse hair, Alopecia Loss of scalp hair and / or lateral eyebrow hair www.drsarma.in 51 Clinical Signs of Hypothyroidism Coarse Hair; Dry cool and pale skin Goitre (not in all cases), Hoarseness of voice Non-pitting oedema (myxoedema) Puffiness of eyes and face Delayed relaxation of Deep tendon reflexes Slow hoarse speech and slow movements Thinning of lateral 1/3 of eye brows Bradycardia, pericardial effusion www.drsarma.in 52 Xanthomata Tuberous Xanthoma Xanthelasma www.drsarma.in 53 Myxoedema with Carotineamia www.drsarma.in 54 Hypothyroidism and Hypercholesterolemia 14% of patients with elevated cholesterol have hypothyroidism Approximately 90% of patients with overt hypothyroidism have increased cholesterol and / or triglycerides www.drsarma.in 55 Thyroid Function Tests TSH 1. 2. Free T4 3. Free T3 4. Anti-Thyroid Antibodies 5. Nuclear Scintigraphy 6. FNAC of nodule www.drsarma.in 56 Diagnosis In Primary Hypothyroidism TSH is high. Free thyroid hormone are depressed. In Secondary Hypothyroidism Both TSH and free thyroid hormones are low. Anti bodies in hypothyroidism Anti bodies: Anti thyroid peroxidase [ anti microsomal] antibodies Anti thyroglobulin antibodies. Anti bodies against T3 and T4 in auto immune hypothyroid disease. In primary hypothyroidism; - up to 12 % pt do have anti gastric parietal cell antibodies. - these pts. Can develop pernicious anemia. Generally… Once diagnosis of primary hypothyroidism is made, additional imaging or serologic testing is unnecessary if gland is normal on exam. In secondary hypothyroidism, further testing with pituitary provocative testing and imaging to rule out microadenoma. In general, evidence of decreased levels of more than one pituitary hormone is indicative of a panhypopituitary problem. Treatment-Thyroid Hormone Replacement Levothyroxine can cause increases in resting heart rate and blood pressure So replacement should start at low doses in older and patients at risk for cardiovascular compromise Monitoring thyroid function Most patients can be followed by serial TSH measurements. Changes in TSH levels lag behind serum thyroid levels. So TSH should not be checked sooner than four weeks after adjusting of doses. Full effect of replacement on TSH may not become apparent until eight weeks. Patients with pituitary insufficiency, T3 and T4 can be followed. Goal is to keep thyroid hormone level in middle to upper range of normal. Frequency TSH or Free T4 monitored yearly. No data supports the practice. Usually once stable dosage is established, it remains stable until 60-70 years. In elderly serum albumin levels may decrease, so dosage may have to be decreased by 20%. Less frequent monitoring in young patients and annually in elderly. Thank You!