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Thyroid Disease . Lottie Wright. Thyroid Anatomy. -2 lobes, Isthmus -Formed from diverticulum of floor of pharynx -Follicular cells -C5-T1 -2 Arteries -3 Veins -PSNS – vagus nerve -SNS – cervical trunk -Recurrent laryngeal nerve -4 parathyroid glands.
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Thyroid Disease Lottie Wright
Thyroid Anatomy -2 lobes, Isthmus -Formed from diverticulum of floor of pharynx -Follicular cells -C5-T1 -2 Arteries -3 Veins -PSNS – vagus nerve -SNS – cervical trunk -Recurrent laryngeal nerve -4 parathyroid glands
Quick note on the Parathyroid glands • 4 • Posterior to thyroid • Secrete parathyroid hormone in response to low ionised calcium levels (-ve feedback) • PTH – increase osteoclast activity releases calcium and phosphate from the bones • Increase calcium and decreased phosphate reabsorption in the kidney • Increase active vitamin D3 production • OVERALL INCREASE CALCIUM AND DECREASE PHOSPHATE.
Hormone Pathway Hypothalamus TRH Anterior Pituitary TSH Thyroid -ve feedback T3 and T4
T3, T4, TBG?! • T4 = Thyroxine = PROHORMONE (80%) • T3 = Triiodothyroxine = ACTIVE (20%) • Iodine containing modified amino acids • T4 T3 in peripheral tissues by: • beta-deiodination • STRESS e.g. acute/chronic sickness, post-surgery, high cortisol, diabetes T4 reverse T3 (rT3), no endocrine action. Regulation of T4 levels e.g. to conserve energy.
Plasma Proteins • T3 & T4 bound to Plasma Proteins in the bloodAlbumin, Thyroxine Binding Globulin • 0.05% T4 free, 0.5% T3 free • Total plasma hormone concentration is dependent on concentration of binding protein. • TBG = pregnancy • TBG = liver and kidney disease
Action of thyroid hormone • Work via intracellular receptors and DNA • Increase basal metabolic rate • Increase number of adrenergic B-receptors in tissuesTissues more responsive to catecholamines • In FETUS – responsible for maturation of bones, lungs, brain.Lack thyroid function ‘cretinism’low IQ, poorly formed bones
Case 1 – 37 year old female Sally • 4 week history of: • Weight loss despite increased appetite • Irritability • ‘Feeling hot and clammy’ • Diarrhoea • Palpitations • Tremor • Examination: • Fast pulse • Fidgeting • Thin hair • Palmar erythema • Eye signs…
HYPERTHYROIDISM • Prevalence 2% • M:F = 5:1 • Most common in middle age. • Causes:99% intrinsic thyroid disease rather than pituitary origin. • Graves’s DiseaseToxic Nodular GoitreToxic Adenoma
Investigations • TSH – undetectable (0.5-5.7mU) • Free T4 – 40pmol/L (10-25 pmol/L) • Free T3 – 20 pmol/L (3.5 – 7.5 pmol/L) • Thyroid Peroxidase Antibody +ve(Don’t routinely test for TSH receptor Antibodies) • ImagingThyroid Uptake Scan
Grave’s Disease (75%) T4 TSH • A cause of ‘thyrotoxicosis’ • Autoimmune IgGantibodies to TSH receptor on thyroidStimulates increased T4 production-ve feedback decreased TSH, therefore undetectable • DiffuseGoitre • 20-50% concordance MZ twins • Environmental triggers:High Iodine IntakeSmokingStress
Thyroid Eye Disease Pretibial myxoedema Thyroid Acropachy
Toxic Multi-nodular Goitre (15%) • More common in elderly & iodine deficient areasLow T4 production Increased TSH hyperplasia of thyroid tissue (multinodular) predisposition to TSHr mutation • Thyroid hormone secreting nodules • Nodular goitre
Hyperthyroid treatment • Beta-blockers for rapid symptom control • 2 treatments, equally effective • Titration of carbimazole for 4/52, reduce based on TFTs every 1-2 months • ‘Block and replace’ – carbimazole + levothyroxineReduced risk of iatrogenic hypothyroidism • 12-18 months of treatment • 50% relapse and require... • Radioiodine – thyroid traps iodine, destroys cells • Surgery –thyroidectomy +/- replacement therapy.Euthyroidpts onlyComps: vocal cord palsy
Differential Diagnosis of Hyperthyroidism • VAGUE! • Difficult to distinguish mild case from anxiety states • Use clinical signsEye signs, goitreetcWeight loss despite normal/increased appetite.
Thyroid Eye Disease (Thyroid orbitopathy) • Affects whole orbit- 6 extra-ocular muscles- lacrimal gland- fatty tissues • Target cells express TSHrAutoantibodies attack fibroblasts proliferate, secrete glycosaminoglycans, form collagen • Diagnosis based on clinical features80% have been hyperthyroid20% ‘euthyroid’ • RFS: SMOKING, female, radioactive iodine
Clinical features • Soft tissue inflammationConjunctivaloedema& redness, eyelid oedema, lacrimal gland enlargement • Proptosis • Eyelid changesLid lag, lid retraction, lateral flare • Radiological featuresfusiform swelling, sparing of tendons, inflammed tissues – shows up white. • MyopathyInflammed extra-ocular musclesDIPLOPIA • Compressive optic neuropathyreduced visual acuity, reduced colour vision, visual defect
Case 2 – 46 year old female Brenda • 6 month history of: • Weight gain • Dry hair and skin • Constipation • Always feeling cold • Fatigue • Low mood • On Examination: • Puffiness of face • Pallor • Slow pulse • Coarsening and shedding of hair BRADYCARDIC Reflexes slow to relax, Ataxia (cerebellar), Dry thin hair/skin, Yawning/drowsy, Cold hands/cold intolerance, Ascites + non-pitting oedema, Round puffy face and hand/obese, Defeated demeanour, Immobile +/- Ileus, Congestive cardiac failure.
HYPOTHYROIDISM • Prevalence 1-5% • Incidence 2/1000 • M:F = 1:5 • Most common middle age • Causes:Primary (thyroid)Secondary (pituitary gland)Autoimmune/ Radio-iodine treatment for hyperthyroidismWorldwide- - iodine deficiency
Investigations • TSH – 23.0 (0.5-5.7 mU/L) – Important for 1’/2’ cause • Free T4 – 2.0 (10-25 pmol/L) • Free T3 – 3.0 (3.5-7.5) • TPO antibodies +ve
Hashimoto’s Thyroiditis T4 TSH • Autoimmune • Autoantibodies to thyroid peroxidase enzyme (TPO) • Diffusegoitre • Decreased T4 production by disease thyroid, feedback to pituitary leads to increased TSH production.
Atrophic Hypothyroidism T4 TSH • Autoimmune • Anti-thyroid Auto-antibodies lymphoid infiltration atrophy and fibrosis • No goitre present • Associated with other autoimmune conditions • Pernicious anaemia, vitiligo
2’ hypothyroidism due to 1’ hypopituitarism • Failure of anterior pituitary gland to produce TSH • Understimulation of thyroid to produce T4 • Biochemistry:Low T4, Low TSHTreat pituitary! T4 TSH
Hypothyroid Management • Replacement therapyfor life • Levothyroxine, Starting dose dependent on age, fitness and cardiac performance. • 6/52 reviewOnce normal, check TSH yearlyEnzyme inducers increase metabolism of thyroxine
Complications • Thyroid Crisis (<2%) • Rapid deterioration of hyperthyroidism • 10% mortality • Fever, anxiety, agitation, confusion, tachycardia • Treat before biochemistry results return. • Often provoked by minor stress/infection/surgery • May require ICU admission • B-blockers, carbimazole, iodine, IV glucocorticoids to stop thyroxine production
Myxoedema Coma (rare) • >50% mortality • Hypothermia, confusion, coma • Treat before biochemistry results • IV T3 • Full supportive therapy
Prognosis • Hyperthyroidism: Untreated = 30% mortality • Post treatment = 3x increased risk of osteopaenic # 1.5 x increased risk of CV disease • Hypothyroidism
OSCE: Thyroid Examination • Introduce and wash hands • General ExaminationAppropriately dressed/ behaviour, Skin, Hair, Body shape, • HandsThyroid Acropachy, sweating, onycholysis, palmar erythema, tremor, pulse • EyesPeriorbitaloedema, Exophthalmos from sides and behind, assess CN 2,3, 6, lid lag by following finger • NeckSwelling, scars, hyperaemia, venous distention, stick out tongue • PALPATE Temperature, swallowing, stick out tongue *, swelling (describe!), lymph nodes, tracheal deviation • Thyroid Bruit, percuss for retrosternal goitre • Offer to assess Pretibial myxoedema, tendon reflexes, review ECG • Review any biochemistry available
QUIZ • 2 causes of hyperthyroidism? • Graves’s Disease, Toxic MultinodularGoitre • 2 causes of hypothyroidism? • Atrophic Hypothyroidism, Hashimoto’s thyroiditis • 3 Treatments of Hyperthyroidism • Carbimazole +/- Levothyroxine, Radio-iodine, Sub-total Thyroidectomy • Feature of thyroid eye disease (SPERMC) • Soft tissue inflammation, Proptosis, Eyelid changes, Radiological Changes, Myopathy, Compressive Optic Neuropathy • What happens to TSH & T4/T3 in the following:Grave’s DiseaseHashimoto’s ThyroiditisSecondary hypothyroidism • GD: Low TSH, Raised T4/T3HT: High TSH, Low T4/T3SH: Low TSH, Low T4/T3