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Thyroid Disorders

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Thyroid Disorders

  1. 1. Thyroid disorders By Dr. Osman Bukhari
  2. 2. <ul><li>Synthesis & release of thyroid hormones </li></ul><ul><li>1- Trapping of iodine in z gland </li></ul><ul><li>2- Organification of iodine by peroxidase </li></ul><ul><li>3- Coupling of mono & diiodotyrosine to form T4 & T3 </li></ul><ul><li>4- Release of T4 & T3 </li></ul><ul><li>* Thyroid secretes mostly T4 & very little T4, but 90% of circulating T3 ( most active hormone) is derived from peripheral deiodination of T4 to T3 in z liver, kidney & muscles. </li></ul>
  3. 3. <ul><li>*Over 99% of circulating hormones are bound to TBG, thyroid binding preaMlb. & albumin. Only free hormone enter cells binding to specific nuclear receptors for tissue action. </li></ul><ul><li>Hypothalamic- Pituitary- Thyroid axis :- </li></ul><ul><li>1-TRH stimulates release of TSH </li></ul><ul><li>2-TSH stimulates TSH receptors to increase synthesis & release of stored T3 & T4 increasing their level in z plasma </li></ul><ul><li>3- T3 & T4 feed back on z pituitary and hypothalamus to reduce synthesis of TRH & TSH </li></ul>
  4. 4. <ul><li>Hyperthyroidism </li></ul><ul><li>This refers to z clinical manifestations with increased serum levels of T3 & T4. </li></ul><ul><li>Causes :- </li></ul><ul><li>1- Graves, disease +++ </li></ul><ul><li>- A.I disease characterized by increased secretion & release of thyroid hormones </li></ul><ul><li>- Associated with vascular goitre & may be accompanied by infiltrative ophthalmopathy & less commonly dermopathy & acroachy </li></ul>
  5. 5. <ul><li>- F : M = 9:1, 20 -40 years </li></ul><ul><li>- Pathogenesis is due to TSH receptor antibodies that bind to TSH-R in z gland and stimulate hyperfunction. TSH-R Ab are present in 80 % of pat. TPO & thyroglobulin Abs are increased in most pats. </li></ul><ul><li>- Pats with Graves disease are at increased risk of developing other A.I diseases. </li></ul><ul><li>- The natural history is that of remission and relapses. Many pats eventually Hypothyroid </li></ul>
  6. 6. <ul><li>2- Toxic adenomas or nodules : </li></ul><ul><li>a- Toxic multinodular goitre </li></ul><ul><li>b- Toxic solitary nodule or adenoma (Plumer,s disease) </li></ul><ul><li>* they are not accompanied by ophthalmopathy or dermopathy (due to glycosaminoglycan & lymphocytic infiltration. Thyroid Abs are not usually present in z plasma. </li></ul><ul><li>3- Sub acute thyroiditis (de Quervain,s thyroiditis) : there are general symptom of inflammation, neck pain, thyroid tenderness, high ESR and initial transient hyperthy. Is followed by transient hypothr. </li></ul>
  7. 7. <ul><li>4- Iodine induced hyperthyroidism (Jodbasedow disease)_ occur in MNG after large doses of iodine e.g. dietary iodine supplements, contrast & drugs like amiodarone </li></ul><ul><li>5- Thyrotoxicosis factitia - from ingestion of exogenous thyroxin. </li></ul><ul><li>6- Strom ovarii-ovarian dermoid & teratomas secreting thyroid hormones autonomously from z contained thyroid tissue </li></ul>
  8. 8. <ul><li>7- Hashimotos,s thyroiditis – causes transient hyperthyroidism </li></ul><ul><li>8- Pregnancy & trophpoblastic tumours – postpartum thyroiditis causing transient hyperthy. Due to release of stored hormones following damage to z thyroid by TPO Abs. Very high levels of hCG stimulate TSH-R in early preg, molar preg, chorioCa & testicular malign. </li></ul><ul><li>9- Metastatic functional thyroid Ca . </li></ul><ul><li>10- Post-irradiation </li></ul><ul><li>11- TSH secreting pituitary tumours . </li></ul>
  9. 9. <ul><li>*** Over 90 % of cases of hyperthy. are caused by Graves, toxic MNG & toxic solitary nodules. </li></ul>
  10. 10. <ul><li>Clinical manifestations of hyperthyroidism: symptoms :- </li></ul><ul><li>- Variable </li></ul><ul><li>-fatigability -irritability - restlessness </li></ul><ul><li>- nervousness - anxiety - palpitation </li></ul><ul><li>- heat intolerance - diarrhea - Wt loss </li></ul><ul><li>- proximal muscle weakness - tremors </li></ul><ul><li>- sweating - menstrual irregularities </li></ul><ul><li>- goitre - hypokaemic periodic paralysis </li></ul><ul><li>- painful eyes, increased lacrimation, exoph photophobia, blurred vision & diplopia </li></ul>
  11. 11. <ul><li>Signs:- </li></ul><ul><li>- goitre with a bruit -hyperkinesis </li></ul><ul><li>- fine finger tremor of out-stretched hands </li></ul><ul><li>- warm sweaty hands - palmer erythema </li></ul><ul><li>- sinus tachycardia with full pulse or AF </li></ul><ul><li>- systolic HT- HF - proximal myopathy </li></ul><ul><li>- lid retraction & lid lag </li></ul><ul><li>-proptosis, exophthalmus keratitis </li></ul><ul><li>- periorbital & conjunctival edema </li></ul><ul><li>- ophhalmoplegia </li></ul>
  12. 12. <ul><li>- pretibial myxedema( in 3% of Graves) </li></ul><ul><li>- thyroid acropachy: clubbing & swollen fingers from periosteal new bone formation </li></ul><ul><li>-onychlysis </li></ul><ul><li>-brisk reflexes </li></ul><ul><li>- gynaecomastia </li></ul><ul><li>**Ophthalmopathy is clinically apparent in 20-40 % of Graves & usually consist of chemosis, conjunctivitis & mild proptosis. </li></ul><ul><li>More severe case occur in 5-10% & have exophthalmus & diplopia. </li></ul>
  13. 13. <ul><li>** The eye sighs, pretibial myxoedema and thyroid acropachy occur only in Graves disease </li></ul><ul><li>** Elderly pats frequently present with AF, tachycardia and/or HF with only few other signs </li></ul><ul><li>** Children frequently present with excessive growth rate, behavioral problems & may show Wt gain </li></ul>
  14. 14. <ul><li>Complications of hyperthyroidism : </li></ul><ul><li>- AF & HF </li></ul><ul><li>- Osteoporosis </li></ul><ul><li>-Hypercalcemia & nephrocalcinosis </li></ul><ul><li>- Hypokalaemic periodic paralysis induced by exercise or heavy CHO ingestion </li></ul><ul><li>- Sexual problems in males </li></ul>
  15. 15. <ul><li>Diff. Diag. of hyperthyroidism : </li></ul><ul><li>- Anxiety </li></ul><ul><li>- Phaeochromocytoma </li></ul><ul><li>- Cardiac with AF refractory o TR </li></ul><ul><li>- Other causes of ophthalmoplegia and exophthalmos </li></ul>
  16. 16. <ul><li>Diag of hyperthyroidism </li></ul><ul><li>- Clinical suspicion confirmed by: </li></ul><ul><li>- Suppressed serum TSH except in 2dry hyperthyroidism </li></ul><ul><li>- Raised serum T4, free T4 or T3 & T3 </li></ul><ul><li>- TSH-R abs, TPO & thyroglobulin Abs are present in most cases </li></ul><ul><li>- Radio-iodine uptake </li></ul><ul><li>- Imaging </li></ul>
  17. 17. <ul><li>Treatment of hyperthyroidism </li></ul><ul><li>1- Antithyroid drugs </li></ul><ul><li>2- Radioiodine </li></ul><ul><li>3- Surgery </li></ul>
  18. 18. <ul><li>Antithyroid drugs </li></ul><ul><li>( Thiourea drugs ) </li></ul><ul><li>They inhibit z formation of thyroid hormones. Generally used for young adults, mild hyperthy, small goitres and preparing pats for surgery & radioactive iodine therapy </li></ul>
  19. 19. <ul><li>1- Carbimazole & z active metabolite methimazole – Also have mild immunosuppressive activity. - Initial dose 40-60mg divided or single </li></ul><ul><li>- SE- rash, nausea, vomiting, arthralgia, </li></ul><ul><li>jaundice & agranulocytosis ( o.1%) </li></ul><ul><li>- It crosses z placenta </li></ul>
  20. 20. <ul><li>2- Propylthiouracil </li></ul><ul><li>- Dose 100-200mg 8-hourly </li></ul><ul><li>- additionally blocks conversion of T4 to T3 </li></ul><ul><li>- SE—rash, nausea, vomiting & agranulo </li></ul><ul><li>Beta blockers </li></ul><ul><li>- Propranolol </li></ul><ul><li>- Dose –40-8mg 8-houly </li></ul><ul><li>- Avoid in bronchial asthma & use with </li></ul><ul><li>care in HF </li></ul><ul><li>- Decrease conversion of T4 to T3 </li></ul>
  21. 21. <ul><li>Treatment regimens </li></ul><ul><li>1- Gradual dose titration </li></ul><ul><li>- Start with z high dose </li></ul><ul><li>- Review after 4-6 Ws & reduce dose </li></ul><ul><li>depending on clinical state & T4 & T3 </li></ul><ul><li>levels </li></ul><ul><li>- Stop BB when clinically & biochem </li></ul><ul><li>euthyroid </li></ul><ul><li>- Review after2-3Ms & reduce carbimaz </li></ul><ul><li>if controlled </li></ul>
  22. 22. <ul><li>- Reduce dose gradually to 5mg over </li></ul><ul><li>6- 24Ms if z disease remained </li></ul><ul><li>controlled </li></ul><ul><li>- When euthyroid on 5mg daily </li></ul><ul><li>discontinue carbimazole </li></ul><ul><li>*Propylthiouracil is used in a similar way. </li></ul><ul><li>2- Block & replace regimen </li></ul><ul><li>- Full doses of antithyroid drugs are given </li></ul><ul><li>e.g. carbimazole 40mg to suppress the </li></ul><ul><li>thyroid completely while replacing </li></ul>
  23. 23. <ul><li>thyroxin 100 mcg daily once z pat is euthyroid & continued for 18Ms </li></ul><ul><li>- This regimen avoids over or under TR </li></ul><ul><li>and offers z immunosuppressive effect </li></ul><ul><li>of carbimazole </li></ul><ul><li>- It is CI in pregnancy as T4 crosses </li></ul><ul><li>placenta less well than carbimazole </li></ul><ul><li>** About 50% relapse after a course of antithyroid TR & long term therapy, surgery or R/I therapy is considered. Those with large single or MNG are unlikely to remit after a course. </li></ul>
  24. 24. <ul><li>Surgery– subtotal thyroidectomy </li></ul><ul><li>Surgery is considered for large goitres unlikely to remit after med TR, pressure symptoms, preg women uncontrolled with low doses of Thiourea, poor compliance with drugs, persistent dug SE & recurrent hyperthy after drugs </li></ul><ul><li>- Pat rendered euthyroid or Ipodate preoperatively </li></ul><ul><li>- Thyroid vascularity is reduced preoperatively by Ipodate or Lugols iodine solution to reduce thyroid crisis </li></ul>
  25. 25. <ul><li>- Complications of surgery include postoperative bleeding &tracheal compression, recurrent laryngeal nerve palsy, hypocalcemia, hypothy & recurrent hyperthy. </li></ul>
  26. 26. <ul><li>Radioactive iodine </li></ul><ul><li>- Now commonly being after child bearing age </li></ul><ul><li>- CI during pregnancy & while breast feeding </li></ul><ul><li>- Dose 200-500 </li></ul><ul><li>- pat rendered euthyroid preoperatively and stop drugs 4 days before </li></ul><ul><li>- Early neck pain, transient hyperthy, progressive incidence of hypothy, worsening of ophthal, ?carcinogenesis. </li></ul>
  27. 27. <ul><li>Hyperthy in pregnancy & neonatal life </li></ul><ul><li>- Maternal hyperthy is uncommon during pregnancy, mild & usually due to Graves </li></ul><ul><li>- TSH-R Abs cross z placenta & stim fetal thyroid, carbimazole also crosses placenta but T4 poorly & so block & replace regim is CI </li></ul><ul><li>- Use smallest necessary dose of drugs and breast feeding while on usual doses is safe. </li></ul><ul><li>- If high doses are needed surgery can be performed, best in z 2 nd trimester. </li></ul>
  28. 28. <ul><li>- A child borne to a mother with Graves may be borne with hyperthy even if she is treated because ABS may still be present. The fetus should be monitored monthly with pulse & hormones </li></ul>
  29. 29. <ul><li>Thyroid crisis or storm </li></ul><ul><li>- Rare, mortality 10%, </li></ul><ul><li>- present with rapid deterioration of hyperthy with hyperpyrexia, extreme restlessness, tachycardia, hypotension, delirium & com </li></ul><ul><li>- precipitated by stress, infection or trauma in a pat inadequately treated or surgery in unprepared pat or R/I therapy </li></ul><ul><li>- Diag is clinical </li></ul><ul><li>- TR include Propranolol, hydrocortisone, </li></ul>
  30. 30. <ul><li>Na iodide orally, Ipodate (inhibit release of hormones & conversion of T4 to T3), IV fluids, lowering temp & high doses of Thioureas. </li></ul>
  31. 31. <ul><li>Hypothyroidism </li></ul><ul><li>Syndrome that results from deficiency of thyroid hormones. F : M =15 : 1 </li></ul><ul><li>It may be primary or secondary to hypothalamic-pituitary disease. </li></ul><ul><li>Primary hypothy : </li></ul><ul><li>1- Autoimmune </li></ul><ul><li>- Atrophic thyroiditis </li></ul><ul><li>- Hashimoto,s thyroiditis </li></ul><ul><li>- Postpartum thyroiditis </li></ul><ul><li>** Associated AI diseases </li></ul>
  32. 32. <ul><li>2- Post-surgery </li></ul><ul><li>3- Post-irradiation ( R/A iodine or external neck irradiation) </li></ul><ul><li>** 1, 2 & 3 account for more than 90% of causes. </li></ul><ul><li>4- Defects of hormone synthesis </li></ul><ul><li>- Iodine deficiency </li></ul><ul><li>- Dyshormonogenesis due to genetic defects in hormone synth e.g. Pendred,s syndrome (hypothy + sensorineural deafness </li></ul>
  33. 33. <ul><li>- Anti thyroid drugs </li></ul><ul><li>- Other drugs e.g. amiodarone, lithium ( inhibit release of thyroid hormones ), interferon </li></ul><ul><li>5- Post sub acute thyroiditis </li></ul><ul><li>6- Infiltration e.g. tumours, sarcoidosis </li></ul><ul><li>7- Food goitrogens e.g. cassavas </li></ul><ul><li>8- peripheral resistant to thyroid </li></ul><ul><li>hormones </li></ul><ul><li>9- Congenital e.g. agenesis. </li></ul>
  34. 34. <ul><li>Secondary hypothy </li></ul><ul><li>1-Hypopituitarism </li></ul><ul><li>2- Isolated TSH deficiency </li></ul><ul><li>** Goitre is absent in atrophic </li></ul><ul><li>thyroiditis, irradiation, after total thyroidectomy & in 2ry hypothy </li></ul>
  35. 35. <ul><li>Clinical features : </li></ul><ul><li>-Hypothy causes S & S referable to all and diagn may be missed if not positively considered. Myxoedema refers to accumulation of mucopolysaccharides, hyaluronic acid & chondroitin SO4 in S/C tissues. </li></ul><ul><li>- The classic picture of slow, dry- haired, thick- skinned, deep voiced pat with Wt gain, cold intolerance, bradycardia & constipation makes z diagn easy, but milder cases are diff to diagn clinically. </li></ul>
  36. 36. <ul><li>Symptoms : </li></ul><ul><li>- Tiredness & malaise - Wt gain/anorexia </li></ul><ul><li>-Cold intolerance - Poor memory </li></ul><ul><li>- Depression - Poor libido </li></ul><ul><li>- Goitre - dry brittle hair </li></ul><ul><li>- Dry coarse skin - Constipation </li></ul><ul><li>- Arthralgia, myalgia, muscle weakness and stiffness - Menorrhagia, oligomenorrhoea or amenorrhoea in females. - deafness </li></ul><ul><li>- Psychosis - Coma </li></ul>
  37. 37. <ul><li>Signs : </li></ul><ul><li>- Mental slowness - Poverty of movement </li></ul><ul><li>- Ataxia - deafness - psychosis </li></ul><ul><li>- Dry thin hair - Loss of lateral eyebrow </li></ul><ul><li>- Hypertension - Hypothermia - HF </li></ul><ul><li>- Bradycardia - Pericardial effusion </li></ul><ul><li>- Ascites & pleural eff—rare - Pallor </li></ul><ul><li>- Cold peripheries - Hard pitting edema </li></ul><ul><li>- Carpal tunnel syndrome - deep voice </li></ul><ul><li>- Periorbital edema - dry carotinemic skin </li></ul><ul><li>- Goitre - OverWt - Anemia </li></ul>
  38. 38. <ul><li>- Proximal myopathy - Myotonia </li></ul><ul><li>- Slow relaxing reflexes </li></ul><ul><li>- Slow growth velocity, poor school performance & arrest of pubertal development in children with hypothy </li></ul><ul><li>Hypothy should be excluded in all pats with menstrual disturbances, infertility and hyperprolactinaemia </li></ul><ul><li>- Hypothy in elderly is diff to differentiate from normal aging </li></ul>
  39. 39. <ul><li>Investigations: </li></ul><ul><li>- High serum TSH confirm z diagn of pry hypothy - very sensitive </li></ul><ul><li>- Low total or free T4 confirms hypothy state as TSH is low or normal in 2ry hypothy </li></ul><ul><li>- High thyroid Abs (TPO & Thyroglobulin) </li></ul><ul><li>- Anemia </li></ul><ul><li>- Hypercholestrolaemia </li></ul><ul><li>- Organ specific Abs </li></ul><ul><li>- Hyponatraemia </li></ul><ul><li>- ECG-S. bradycardia, low voltage, Tw inv & Jw </li></ul>
  40. 40. <ul><li>Complications of hypothyroidism : </li></ul><ul><li>- CAD & HF </li></ul><ul><li>- Increased susceptibility to infection </li></ul><ul><li>- Organic psychosis </li></ul><ul><li>- Infertility—Miscarriage </li></ul><ul><li>- Adrenal crisis may be precipitated by </li></ul><ul><li>thyroid therapy </li></ul><ul><li>- Myxedema coma: Most often seen in elderly women leading to severe hypothermia, hypovent, hypoxia, hyponatr, hypoten and hypercapnia. Convulsions & CNS signs, confusion & coma </li></ul>
  41. 41. <ul><li>It is precipitated by an underlying infection, illness & cold exposure. Mortality is 50 % </li></ul><ul><li>Diff diagn: Hypothy should be considered in unexplained asthenia, menstrual disturbance, constipation, Wt gain, hyperlipidaemia, anemia, refractory HF, ascites & psychosis </li></ul><ul><li>- </li></ul>
  42. 42. <ul><li>Treatment of hypothyroidism </li></ul><ul><li>- T4 is z drug of choice for replacement </li></ul><ul><li>- In young fit pats start with 100mcg/d </li></ul><ul><li>- In small, old or frail start with 50mcg/d </li></ul><ul><li>- In IHD with severe hypothy start carefully with 25mcg/d </li></ul><ul><li>- Increase dose by 25-50 every 1-3W till pat is euthyroid </li></ul><ul><li>- Adequacy of TR is assessed clinically and by TSH & T4 </li></ul>
  43. 43. <ul><li>- Maintenance dose is 100-150 mcg/d with annual TFT. </li></ul><ul><li>- Clinical improvement do not begin before 2W & resolution of symptoms may take 6M </li></ul><ul><li>- TR is life long </li></ul><ul><li>- Myxedema coma –ICU </li></ul><ul><li>- 400mcg IV start, then 1oomcg daily </li></ul><ul><li>- Rewarm pat gradually </li></ul><ul><li>- Hydrocortisone 100mg 8 hourly </li></ul><ul><li>- Glucose to prevent hypoglycemia </li></ul>
  44. 44. <ul><li>- Intubate & O2 if hypovent. Or hypercap. </li></ul><ul><li>Screening for hypothy: </li></ul><ul><li>Routine screening of newborn to detect high TSH as an indicator of Pry hypothy is efficient & cost-effective to prevent cretinism if T4 is started early. </li></ul>
  45. 45. <ul><li>A 30 y lady presented to her GP with increased irritability & anxiety which has been noticed by her husband & colleagues at work over z last 3/12. She lost Wt. despite good appetite & has increased frequency of bowel movements. She feels extremely tired, sweats profusely & can not tolerate hot weather. </li></ul><ul><li>No PH of sig medical problem </li></ul><ul><li>Her parents are diabetic, a sister had thyroid dis and an elderly sister suffers from chronic anemia. </li></ul><ul><li>O/E: she appears agitated & tremulous. Her eyes appear prominent, pulse 104/min & regular, BP 150/70 </li></ul>
  46. 46. <ul><li>Systemic exam . Was normal. </li></ul><ul><li>CBC, urine exam. & blood urea-E were normal </li></ul><ul><li>1- What is z most likely diagn? </li></ul><ul><li>2- Mention additional 3 symptom & signs? </li></ul><ul><li>3- How would neck exam. helps you to reach a diagn? </li></ul><ul><li>4- Tow investigations to confirm z diagn? </li></ul><ul><li>5- Mention a serological investigation to reveal the nature of z underlying dis? </li></ul><ul><li>6- One diff. diagn? </li></ul><ul><li>7- How would you manage this patient? </li></ul>

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