Hyperthyroidism

Hyperthyroidism

1. DR.ADEEL RIAZ PGR SURGERY DEPTT. CPTH, LAHORE. HYPERTHYROIDISM

2. INTRODUCTION: Hyperthyroidism and Thyrotoxicosis are the terms often used interchangeably, however each refers to slightly different conditions.Hyperthyroidism refers to over activity of the thyroid gland, with resultant excessive secretion of thyroid hormones and accelerated metabolism. Thyrotoxicosis refers to the c linical effects of an unbound thyroid hormone, regardless of whether or not the thyroid is the primary source. There are number of pathological causes of hyperthyroidism in children and adults.These include Grave’s disease, T oxic Adenoma, Toxic Multinodular Goitre and Thyroiditis.Of these, Grave’s disease accounts for approx. 60% of cases of hyperthyroidism.To understand the pathophysiology of hyperthyroidism, it is necessary to understand the normal physiology of the thyroid gland.

3. THYROID GLAND: The thyroid gland is a butterfly-shaped endocrine gland that is normally located in the lower front of the neck. The thyroid gland’s job is to make thyroid hormones, which are secreted into the blood and then carried to every tissue in the body. Thyroid hormone helps the body use energy, stay warm and keep the brain, heart, muscles, and other organs working as they should .

4. DEFINITION: Hyperthyroidism is due to increased levels of thyroid hormone i.e. Diffuse Toxic Goitre (Grave’s disease), Toxic Multinodular Goitre (Plummer’s disease) and Toxic Adenoma. According to SANJAY AZAD: Hyperthyroidism is the hyperactivity of thyroid gland with sustain increase in sythesis and release of thyroid hormones. According to WATSON: Hyperthyroidism implies an excessive secretion of thyroid hormones and may called as thyrotoxicosis, but toxic goitre , exophthalmic goitre or Grave’s disease. The term exophthalmic goitre or Grave’s disease are reversal for hyperthyroidism that is accompanied by exophthalmus and extreme nervousness.

5. ANATOMY OF THE THYROID GLAND It is butterfly-shaped located just inferior to larynx in the lower front of the neck. It is composed of right and left lateral lobes, one on either side of trachea, that are connected by isthmus anterior to the trachea. Microscopic spherical sac called thyroid follicles make up most of the thyroid gland. The walls of each follicles consist primarily of cells called follicular cells. The thyroid gland is a highly vascularized organ located in the neck, deep to the platysma , sternothyroid and sternohyoid muscles, and extending from the 5 th cervical (C5) to the Ist Thoracic (T1) vertebrae.

6. ANATOMY OF THE THYROID GLAND The gland consists of two lobes (left and right) connected by a thin, median isthmus overlying the 2 nd to 4 th tracheal rings, typically forming an “H” or “U” shape. Beneath the visceral layer of the pretracheal , deep cervical fascia, the thyroid gland is surrounded by a true inner capsule, which is thin and adheres closely to the gland. The capsule sends projections into the thyroid forming septae and dividing it into lobes and lobules. Dense connective tissue attachments secure the capsule of the thyroid to both the cricoid cartilage and the superior tracheal rings. Arterial supply is by superior thyroid, inferior thyroid and thyroid ima artery, Venous drainage by superior , middle and inferior thyroid veins. Nerves in relation are superior laryngeal and recurrent laryngeal nerve. Lymphatic drainage is by middle and lower deep cervaical and supraclavicular lymph nodes.

7. PHYSIOLOGY OF THYROID GLAND Thyroid gland secretes Tri- iodothyronine (T3) & Thyroxine (T4). Steps involved in synthesis of these hormones are Iodine trapping from blood into the thyrocytes ( Thiocyanates and perchlorates block this step) Oxidation of iodide to inorganic iodine catalyzed by peroxidase enzyme ( Carbimazole,Propylthiouracil and PASA block this step) Formation of iodotyrosines : iodine + tyrosine= MIT ( monoiodotyrosine ) + DIT ( diiodotyrosine ) ( carbimazole inhibits this step) Coupling reactions: coupling of 2 molecules of DIT results in T4 and 1 molecule of DIT + MIT results in T3 (this stage is blocked by carbimazole ) Hydrolysis: Hormones combine with globulin to form thyroglobulin stored in thyroid gland and are released as required by the process of hydrolysis.

8. PATHOPHYSIOLOGY Hyperthyroidism characterized by loss of normal regulatory control of thyroid hormone secretions ↓ Stimulatory action of thyroid in the body, hyermetabolism results ↓ Increase in sympathetic nervous system results ↓ Alteration of secretion & metabolism of hypothalamic pituitary and gonadal hormones ↓ Excessive thyroid hormone stimulates cardiac system and increase of adrenergic receptors activity ↓ Tachycardia, increased cardiac output, stroke volume, adrenegic responsiveness and peripheral blood flow ↓ Resultant state of nutrinional deficiency & - ve Nitrogen balance ↓ Hyperthyroidism

9. HYPERTHYROIDISM A hyper metabolic biochemical state It is a multi system disease with Elevated levels of FT 4 or FT 3 or both What is thyrotoxicosis ? What is hyperthyroidism ? What are the various causes ? How to differentiate the causes ? What is the appropriate treatment ?

10. CAUSES OF HYPERTHYROIDISM Graves Disease – Diffuse Toxic Goiter Plummer’s Disease – Toxic MNG Toxic phase of Sub Acute Thyroiditis - SAT Toxic Single Adenoma – STA Pituitary Tumours – excess TSH Molar pregnancy & Choriocarcinoma (↑↑ β HCG) Metastatic thyroid cancers (functioning) Struma Ovarii ( Dermoid and Ovarian tumours ) Thyrotoxicosis Factitia ; INF, Amiodarone , SSRIs

11. GRAVE’S DISEASE The most common cause of thyrotoxicosis (50-60%). Organ specific auto-immune disease The most important autoantibody is Thyroid Stimulating Immunoglobulin (TSI) or TSA TSI acts as proxy to TSH and stimulates T 4 and T 3 Anti thyro peroxidase (anti-TPO) antibodies Anti thyro globulin (anti-TG) Anti Microsomal and other Autoimmune diseases - Pernicious Anemia, T1DM RA, Myasthenia Gravis, Vitiligo , Adrenal insufficiency .

12. GRAVE’S DISEASE I 123 or TC 99m Normal v/s Graves

13. TOXIC MULTINODULAR GOITRE 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 FT 4 and FT 3 Progresses slowly over time Clinically multiple firm nodules (called Plummer’s disease) Scintigraphy shows - hot and normal areas

14. TOXIC MULTINODULAR GOITRE NUCLEOTIDE SCINTIGRAPHY

15. SUBACUTE THYROIDITIS SAT is the next most common hyperthyroidism – 15% T 4 and T 3 are extremely elevated in this condition Immune destruction of thyroid due to viral infection Destructive release of preformed thyroid hormone Thyroid gland is painful and tender on palpation Nuclear Scintigraphy scan - no RIU in the gland Treatment is NSAIDs and Corticosteroids

16. TOXIC ADENOMA TSA is a single hyper functioning follicular thyroid adenoma. Benign monoclonal tumor that usually is larger than 2.5 cm It is the cause in 5% of patients who are thyrotoxic Nuclear Scintigraphy scan shows only a single hot nodule TSH is suppressed by excess of thyroxines So the rest of the thyroid gland is suppressed

17. TOXIC ADENOMA NUCLEOTIDE SCINTIGRAPHY

18. NUCLEOTIDE SCINTIGRAPHY

19. CLINICAL MANIFESTATIONS OF HYPERTHYROIDISM Those that occur with any type of thyrotoxicosis Those that are specific to Graves disease Non specific changes of hyper metabolism

20. COMMON SYMPTOMS SKIN : warm, may br erythmatous (due to increased blood flow), smooth (due to decrease in keratin), sweaty and heat intolerance, oncholysis (softening of nails and loosening of nail beds), hyperpigmentation (due to increase ACTH secretion) CVS : increased cardiac output (due to increased O2 demand), tachycardia, widened pulse pressure,high output HF. RESPIRATORY : dyspnea on rest or exertion, increased O2 consumption & CO2 production, hypoxemia and hypercarbia,tracheal obstruction,increased pulmonary arterial pressure, resp. muscles weakness, decreased exercise capacity. GIT : malabsortion , steatorrhea , celiac disease, hyperphagia , anorexia, dysphagia, hyperdefecation , weight loss.

21. COMMON SYMPTOMS NEUROMUSCULAR : tremors and hyperactive tendon reflexes REPRODUCTIVE : in females; oligomenorrhea,amenorrhea in males; gynecomastia , decreased libido, erectile dysfunction, decreased or abnormal sperms. PSYCHIATRIC : hyperactivity, emotional liability, anxiety, insomnia, decreased concentration. GENITOURINNARY : urinnary frequency and nocturia .

22. COMMON SIGNS 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 M uscle weakness, Diarrhea, Gynecomastia

23. Specific to Graves Disease Diffuse painless and firm enlargement of thyroid gland Thyroid bruit is audible with the bell of stethoscope Ophthalmopathy – Eye manifestations – 50% of cases Sand in eyes, periorbital edema, conjunctival edema ( chemosis ), poor lid closure, extraocular muscle dysfunction, diplopia, pain on eye movements and proptosis . Dermoacropathy – Skin/limb manifestations – 20% of cases Deposition of glycosamino glycans in the dermis of the lower leg – non pitting edema, associated with erythema and thickening of the skin, without pain or pruritus - called (pre tibial myxedema)

24. MNG and Graves Huge Toxic MNG Diffuse Graves Thyroid

25. Higher grades of Goiter Toxic MNG (Diffuse) Graves

26. Grade IV Toxic MNG Huge Toxic MNG Huge Toxic MNG

27. Proptosis Lid lag Thyroid Ophthalmopathy

28. Ophthalmopathy in Graves Periorbital edema and chemosis

29. Severe Exophthalmia

30. Thyroid Dermopathy Pink and skin coloured papules, plaques on the shin

31. Clubbing and Osteoarthropathy Thyroid Acropathy

32. Onycholysis

33. NON SPECIFIC CHANGES Hyperglycemia, Glycosuria Osteoporosis and hypercalcemia ↓ LDL and Total Cholesterols Atrial fibrillation, LVH, ↑ LV EF Hyper dynamic circulatory state High output heart failure H/o excess Iodine, amiodarone , contrast dyes

34. DIAGNOSTIC TESTS Thyroid Function Tests (TFTs) Thyroid antibodies – by ELISA Ultrasound Fine needle aspiration cytology (FNAC) Thyroid Nucleotide Scintigraphy

35. THYROID FUNCTION TESTS Serum TSH is supressed in hyperthyroidism (<0.05 mU /L) T3 & T4 are raised almost always from their normal levels i.e. T3=1.5-3.5 nmol /L & T4=55-150 nmol /L but T3 is more sensitive. TSH receptor antibodies are not measured routinely,but are commonly present. In developing hyperthyroidism, the free T3 concentration is more sensitive indicator of developing disease than T4,and the former is therefore preferred for confirming hyperthyroidism that has already been suggested by a supressed TSH result.

36. ULTRASOUND Ultrasound can be used to assess a thyroid nodule. Its advantage over physical examination lies alone in its ability to distinguish solid from cytic nodules, whether more than one nodule exists,and the exact size and extent of nodules. Infact , ultrasound can be used to access the size and shape of the thyroid itself. Because of recent advances in this form of imaging, ultrasound has become a sensitive modality, particularly when assessing size and numbers of nodules.

37. FINE NEEDLE ASIRATION Provided adequate sample is removed on biopsy, FNAC of the thyroid nodule can be used to categories tissue into benign, malignant, thyroiditis, follicular neoplasm. This technique has reduced unnecessary operative procedure in patients with benign disease and increased the probability that surgery will be performed on those with malignant disease .

38. THYROID NUCLOTIDE SCINTIGRAPHY The throid gland tissue can take up iodine and certain other molecules. When radioactive isotopes of these substances are swallowed or injected into blood stream, they are taken up by thyroid gland. As they decay, a special camera can detect the energy that is released, creating a picture of the thyroid gland. Most commonly used isotopes are Iodine-123, 99m- Technetium, 131- iodine.

39. Measure TSH and FT4  TSH,  FT4 Measure FT3 Primary (T4) Thyrotoxicosis High Pituitary Adenoma FNAC, N Scan Normal  TSH, FT4 N  TSH,  FT4 T3 Toxicosis Features of Grave’s Yes Rx. Grave’s No Single Adenoma, MNG Low RAIU  RAIU Sub Acute Thyroiditis, I 2 , ↑ Thyroxine F/u in 6-12 wks Algorithm for Hyperthyroidism

40. Treatment Options Symptom relief medications Anti Thyroid Drugs – ATD Methimazole , Carbimazole Propylthiouracil (PTU) Radio Active Iodine treatment – RAI Rx. Thyroidectomy – Subtotal or Total NSAIDs and Corticosteroids – for SAT

41. Symptom Relief Rehydration is the first step β – blockers to decrease the sympathetic excess Propranalol , Atenelol , Metoprolol Rate limiting CCBs if β – blockers contraindicated Treatment of CHF, Arrhythmias Calcium supplementation Lugol Iodine solution for ↓ vascularity of the gland

42. Anti Thyroid Drugs (ATD) Imp. considerations Methimazole Propylthiouracil Efficacy Very potent Potent Duration of action Long acting BID/OD Short acting QID/TID In pregnancy Contraindicated Safely can be given Mechanism of action Iodination, Coupling Iodination, Coupling Conversion of T 4 to T 3 No action Inhibits conversion Adverse reactions Rashes, Neutropenia Rashes, ↑Neutropenia Dosage 20 to 40 mg/ OD PO 100 to 150mg qid PO

43. How long to give ATD ? Reduction of thyroid hormones takes 2-8 weeks Check TSH and FT 4 every 4 to 6 weeks In Graves, many go into remission after 12-18 months In such pts ATD may be discontinued and followed up 40% experience recurrence in 1 yr. Re treat for 3 yrs. Treatment is not life long. Graves seldom needs surgery MNG and Toxic Adenoma will not get cured by ATD. For them ATD is not the best. Treat with RAI.

44. Radio Active Iodine (RAI Rx.) In women who are not pregnant In cases of Toxic MNG and TSA Graves disease not remitting with ATD RAI Rx is the best treatment of hyperthyroidism in adults The effect is less rapid than ATD or Thyroidectomy It is effective, safe, and does not require hospitalization. Given orally as a single dose in a capsule or liquid form. Very few adverse effects as no other tissue absorbs RAI

45. Radio Active Iodine (RAI Rx.) I 123 is used for Nuclear Scintigraphy ( Dx .) I 131 is given for RAI Rx. (6 to 8 milliCuries ) Goal is to make the patient hypothyroid No effects such as Thyroid Ca or other malignancies Never given for children and pregnant/ lactating women Not recommended with patients of severe Ophthalmopathy Not advisable in chronic smokers

46. Surgical Treatment Subtotal, Near Total & Total Thyroidectomy Hemi Thyroidectomy with contra-lateral subtotal ATD and RAI Rx are very efficacious and easy – so Surgical treatment is reserved for MNG with Severe hyperthyroidism in children Pregnant women who can’t tolerate ATD Large goiters with severe Ophthalmopathy Large MNGs with pressure symptoms Who require quick normalization of thyroid function

47. Preoperative Preparation ATD to reduce hyper function before surgery β eta blockers to titrate pulse rate to 80/min LUGOL’s solution 1 to 2 drops bd for 14 days This will reduce thyroid blood flow And there by reduce per operative bleeding Recurrent laryngeal nerve damage Hypo parathyroidism are complications

48. 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.

49. Thyrotoxicosis Factitia Excessive intake of Thyroxine causing thyrotoxicosis Patients usually deny – it is willful ingestion This primarily psychiatric disorder May lead to wrong diagnosis and wrong treatment They are clinically thyrotoxic without eye signs of Graves High doses of Thyroxine lead to TSH suppression This causes shrinkage of the thyroid Stop Thyroxine and give symptom relief drugs

50. Algorithm for Thyroid Nodule Thyroid Nodule Low TSH Normal TSH TC 99 Nuclear Scan FNAC or US guided biopsy Hot Nodule Cold Nodule RAI Ablation, Surgery or ATD Non diagnostic – repeat FNAC Surgery or Cytology Cyst Benign T4 suppression Suspicious or follicular Ca Malignant Surgery 4% 10% 69% 17%

51. Summary of Hyperthyroidism Hyperthyroidism Age % Enlarged Pain RAIU Treatment Graves (TSI Ab eye, dermo, bruit) 20 - 40 60% Diffuse None ↑↑ ATD – 18 m Toxic MNG > 50 20% Lumpy Pressure ↑ RAI, Surgery Single Adenoma 35 - 50 5% Single None ± RAI, ATD S Acute Thyroiditis Any age 15% None Yes ↓↓ NSAID, Ster. TSH is markedly low, FT4 is elevated