HYPERTHYROIDISM: EPIDEMIOLOGY Australia -Around 1 in 20 people will experience some form of thyroid dysfunction in their lifetime.

-Around 2 in every 100 women will experience some degree of hyperthyroidism. -Its likely that at any time there are approximately 850,000 Australians with thyroid disease of some kind, often going undiagnosed. United States -Graves disease is the most common form of hyperthyroidism (60-80% of thyrotoxicosis). The annual incidence is 0.5 cases per 1000 persons during a 20-year period, with the peak occurrence in people aged 20-40 years. -Toxic multinodular goiter (15-20% of thyrotoxicosis) occurs more frequently in regions of iodine deficiency. Most persons in the U.S. receive sufficient iodine, and the incidence of toxic multinodular goiter is less than the incidence in areas of the world with iodine deficiency. -Toxic adenoma is the cause of 3-5% of cases of thyrotoxicosis. International -The incidences of Graves disease and toxic multinodular goiter change with iodine intake. -Compared with regions of the world with less iodine intake, the U.S. has more cases of Graves disease and fewer cases of toxic multinodular goiters. Race Autoimmune thyroid disease occurs with the same frequency in Caucasians, Hispanics, and Asians, and it occurs less frequently in the black population. Sex All thyroid diseases occur more frequently in women than in men. Graves autoimmune disease occurs in a male-to-female ratio of 1:5-10. The male-to-female ratio for toxic multinodular goiter and toxic adenomas is 1:2-4. Age -Autoimmune thyroid diseases have a peak incidence in people aged 20-40 years. -Toxic multinodular goiters occur in patients who usually have a long history of nontoxic goiter and who therefore typically present when they are older than 50 years. -Patients with toxic adenomas present at a younger age. Thyroid cancer -Thyroid cancer is the most common endocrinological malignancy -More common in women than men. -Incidence rates vary geographically, with the highest rates occurring in North America (8.1 per 100,000 females) and the lowest rates in Western Africa (1.4 per 100,000 females). Malta has the highest incidence rate in the European Union, with 12.6 per 100,000 females affected, compared to the rate in the UK of 3.1 per 100,000. -In US, thyroid cancer accounts for 1% - 1.5% of all new cancer cases reported annually. It is estimated that about 30,000 new cases of thyroid cancer are diagnosed annually in the US and about 1400 people die of the disease. The median age at diagnosis is 40-45 years.

Iodine and Thyroid Iodine: Not created by the body needs to be part of diet Found in bread, iodised table salt, saltwater fish, seaweed, soy milk Over 80 years, worldwide efforts have been made to eliminate iodine-deficiency. Strategies include: o Iodized salt o Iodine in bread (Australia and NZ) o Iodine injections in areas without wide-spread iodized salt access o Iodination of water supplies Essential for making thyroid hormone T4 and T3

Iodine deficiency can cause: Goitre o Without adequate iodine, thyroid progressively enlarges to keep up with demand for thyroid hormone production o Most common cause of goitre o Can lead to hyperthyroidism Hypothyroidism o Most common cause of hypothyroidism o As bodys iodine levels fall, hypothyroidism may develop since iodine is essential for making thyroid hormone Pregnancy-related problems o Iodine is important in pregnancy or during infancy o Even mild iodine deficiency has been associated with miscarriage, stillbirth, preterm delivery and congenital abnormalities in their babies (mental retardation, problems with growth, hearing and speech) o In severe iodine deficiency a syndrome called cretinism can occur (permanent brain damage, mental retardation, deaf mutism, spasticity and short stature); not seen in Australia

Iodine excess: Can trigger autoimmune thyroid disease and hypothyroidism Theory: o High iodine intake can initiate and worsen infiltration of the thyroid of lymphocytes (due to chronic irritation / injury). o Large amounts of iodine blocks the thyroids ability to make hormone People from iodine-deficient regions who move to iodine-sufficient regions may also experience problems since their thyroids have become very good at taking up and using small amounts of iodine iodine-induced hyperthyroidism Potential sources of excess iodine: Medications (amiodarone) Radiology procedures (iodinated intravenous dye) Diet Iodine controversy: too much vs not enough Small risks of chronic iodine excess are outweighed by the substantial hazards of iodine deficiency

Pathophysiology nikjaja

Three main types of clinical thyroid disease: 1. Secretory malfunction: hyper- or hypothyroidism 2. Swelling of the entire gland: goitre 3. Solitary masses: one large nodule in a nodular goitre, adenoma or carcinoma

Types of thyroid cancer (Sara) Papillary & Follicular ca (well-differentiated thyroid ca) Slow-growing tumour of follicular cells Histological psammoma bodies in 50% Propensity for local invasion & metastases Most common thyroid ca (~80%) (3x > common in women) Appear s after 10-20 year latency RF: (childhood) radiation exposure, Hashimoto thyroiditis

Medullary thyroid ca (MTC) Tumour of parafollicular (C cells) Histological amyloid deposits in stroma (green bifringence on Congo red staining) Represents 5% of thyroid malignancy (75% sporadic, 25% familial) Mostly arise in middle & upper 1/3 of lobes (sporadic-unilat, familial- both) Elevated serum calcitonin levels are diagnostic Prognosis worse cf well-differentiated thyroid ca

Anaplastic thyroid ca One of the least common (1.6%) Rapidly growing thyroid mass Histologically highly variable appearance focal areas of necrosis & haemorrhage Most aggressive biological behaviour + Worse survival rates for all malignancies in general Present in 6th-7th decade of life w symptoms of local invasion Primary Thyroid Lymphoma Represent 2-5% of thyroid malignancies Mostly non-Hodgkins B cell tumours 2nd most common = low grade malignant lymphoma of MALT Assoc. w Hashimotos thyroiditis Sarcoma of thyroid gland Uncommon, aggressive tumours arising in stromal or vascular tissue in gland Important to dy/dx this from anaplastic thyroid ca Unresponsive to chemo, recurrence common, prognosis poor Reference eMedicine

Investigations Thyroid Function Tests Test TSH Total T4 Free T4 Total T3 Free T3 Thyroid Auto-Ab TSI Thyroglobulin

Eric Comment Test of choice Bound & Free T4 Functional (Free) T4 Only in HYPER evaluation Rarely used +ve in Hashimoto disease +ve in Graves disease Follow-up thyroid Cancer Normal Value 0.3-5.0 mIU/L 5.0-12.5 g/dL 0.7-2.0 ng/dL 80-180 ng/dL 2.3-4.2 pg/mL Titre < 1:100 < 1.3 (index) (Depends)

Principles: -Correlate w Hx, Ex (Sg, Sx of HYPER, HYPO) -Disease prevalence 0.6% (1:1 HYPER:HYPO) -Co-morbid Inaccurate? Rpt post-acute -TSH first test Abn? Free Thyroxine (T4) -Drugs (iodine contrast, esp inpatient) Abn? TFT Algorithm (Of Sorts!!) [ ] [] [ ] [] [ ] [ ] RAI [ ] [ ] [ ] [ ] [ ] [ ] AAb "-ve" "+ve"

Further Evaluation -HYPER RAIU +/- scan -Nodule FNA/FNB -HYPO Auto-Ab (+ve = Hashimoto) -Subclinical HYPO Rpt TFTs in 6m -Sick Euthyroid Rpt TFTs post-acute

Severe Illness / Drugs (Iodine) / Idiopathic Hashimoto Thyroiditis Subclin HYPO / Insufficient T4 Rx THS-oma / Peripheral Resistance Further workup if CNS disease suspected Central HYPO / Severe Ill Exogenous T3 T3 Toxicosis / Plummer disease / Toxic adenoma Drugs / Subclin HYPER (+Recovery) / Non-Thyroid Thyroiditis / Severe Ill / Exogenous T4 / Drugs (I) Graves / Plummer (TNG) / Toxic Adenoma Thyroiditis / Severe Ill / Exogenous T4 / Drugs (I) Graves / Plummer (TNG) / Toxic Adenoma

[ ]

FT4

TSH

[ ] <0.3

[] FT4

T3

[] / [ ] [ ] RAI

[ ] (< 0.1 mIU/L)

RAI

Thoracic Outlet Syndrome Provocation Tests Adsons maneuver, Wright test, Roos stress test Imaging & Nerve Study X-ray, MRI, EMG/Histology, Conduction, CT Angiography, etc. HYPERTHYROIDISM Management Aim of Treatment decrease hormone overproduction and block peripheral effects of excess hormones

Mechanism

Indications

Contraindications

Side Effects /Complications

Drugs : Thioureas/ Thionamides Examples carbimazole, propylthiouracil and methimazole Inhibits the iodination of tyrosine on thyroglobulin, which consequently decreases T3/T4 synthesis Also inhibits deiodination of thyroxine (prevents it from becoming triiodothyronine) Orally active Decrease in thyroid hormones only occurs after the bodys stores have been depleted (weeks) The half life of T4 is about 7 days Does not effect exopthalmus Iodine/Iodide Small amounts in the diet are necessary for thyroid function High doses inhibit release of T3 and T4 Short term treatment Only inhibits hormones for a few days or weeks Thyrotoxic crisis Preparation for thyroidectomy Allergic reactions Prolonged use (particularly for Graves Disease) Young patients (<40) Pregnancy Thionamides cross the placenta and can cross into milk Carbimazole>propylt hiouracil Causes congenital hypothyrdoism (baby is born with goitre and cretinism) Agranulocytosis Rashes (2-25%) Headaches, nausea, jaundice and joint pain Agranulocytosis

Radioiodine/ Radioactive

Orally active Taken up and accumulated by thyroid Incorporated into thyroglobulin Emits -particles (localised cytotoxic action) Half life 8 days approx Does not affect thyroid hormone levels Reduces some of the signs and symptoms of

Recurrent Hyperthyroidism Thyroid carcinoma Older patients

Pregnancy Childhood

Hypothyroidism Thyroid Cancer

Symptomatic Relief (-adrenoceptor antagonists eg.

In short term while waiting for thionamides and iodine to take effect

Propranolol, metoprolol or atenolol)

hyperthyroidism Tachycardia Arrythmias Angina Tremor Agitation

For hyperthyroid crisis Preparation for thyroidectomy

HYPOTHYROIDISM Management

Dilini

Aim of Treatment increase thyroid hormone or replace hormone

Mechanism

Indications

Contraindications

Side Effects /Complications Angina Arrythmias Heart Failure Oesteoporosis?? Due to overreplacement of thyroid hormone

Thyroxine (T4) (Levothyroxine oroxine)

Orally Active Action Maximum effect in 10 days Duration of action = 3 weeks

For all symptomatic patients with hypothyroidism

Large doses are contraindicated in the elderly Due to risk factors -

Triiodothyronine (T3)

Hypothyroid crisis Eg. Myxoedema coma Used via i.v

Complications

Jess

Hyperthyroidism Thyrotoxic cardiomyopathy heart failure o May also be related to high-output HF Angina AF o seen in 25%, warfarinise unless contraindicated, mx: control hyperthyroidism o Most common in pts >40 Osteoporosis o Due to bone mineral loss o Severity is related to time of untreated hyperthyroidism Gynaecomastia Thyroid storm o Treatment includes beta-blockers, antithyroid drugs, supportive care, and corticosteroids; an endocrine specialist should be consulted

Opthalmopathy o Retro-orbital inflam + lymphocyte infiltration swelling of the contents of the orbital contents o May occur if pt is hypo/hyper/euthyroid

Complications of hypothyroidism Angina o High initial dose of levothyroxine Resistant hypothyroidism o Generally due to non-compliance AF o Over-tx Osteoporosis o Over-tx Myxoedema coma o Generally occurs an older pts w multiple co-morbidities and a long period of untreated illness o Life-threatening condition where untreated, severe hypothyroidism rapidly deteriorates o Precipitated by another underlying illness Adrenal crisis o Levothyroxine tx in the setting of adrenal insufficiency o Treat initially w glucocorticosteroids Tx-related thyrotoxicosis o Over-tx Post-op complications (general) Pain Pyrexia o Atelectasis (mx: physio, NOT abx) o Tissue damage o Necrosis o Infection Do a thorough infection screen (pneumonia, wound, abdo [peritonism], UTI, IV lines, meningism, endocarditis) o DVT o Choose Ix based on clinical findings Confusion o Hypoxia o Drugs (opiates, sedatives, &c.) o Urinary retention o MI o Stroke o Infection o EtOH withdrawal o Liver/renal failure Dyspnoea/hypoxia o Pneumonia/pulmonary collapse/aspiration o LVF (MI/fluid overload) o PE o Pneumothorax 2ary to CVP line or IC anaesthetic block) BP drop o Compare to BP pre-op o Hypovolaemia (replace fluid losses w/ colloid) o Haemorrhage (check wound sites for evidence) o 2ary to MI, PE o Consider sepsis and anaphylaxis Oliguria o Urinary retention (common) replace lost fluids o Renal failure following shock, nephrotoxic drugs, trauma, transfusion o If anuria: consider malsited cathether, obstruction, or two ureters tied during surgery N/V o Mechanical obstruction o Paralytic ileus o Medications Haemorrhage o 1ary Continuous bleeding, starting during surgery. Replace blood loss and if severe, return to theatre for haemostasis o Reactive Haemostasis appears secure until BP rises and bleeding starts. Replace blood and re-explore wounds o 2ary Occurs 1-2 weeks post-op and is the result of infection Wound dehiscence Incisional hernia (abdominal surgery)

Post-op complications (Thyroid surgery) Recurrent and/or superior laryngeal nerve pals Hypoparathyroidism hypocalcaemia Hypothyroidism Thyroid storm Tracheal obstruction due to haematoma in the wound