Thyroid Diseases PDF

ENDOCRINOLOGY Thyroid Gland Diseases Disorders of the Thyroid Gland Thyroid Anatomy and Physiology: o In healthy adults, the thyroid gland consist of two lobes, connecting by midline isthmus, each thyroid lobe normally measures up to 5...

ENDOCRINOLOGY Thyroid Gland Diseases Disorders of the Thyroid Gland Thyroid Anatomy and Physiology: o In healthy adults, the thyroid gland consist of two lobes, connecting by midline isthmus, each thyroid lobe normally measures up to 5 cm in length, 2 cm in width, and 2 cm in depth; the entire gland weighs 10 to 20 grams. o Histologically, the gland consist of two type of cells: 1. The parafollicular C cells secrete calcitonin, which is of no apparent physiological significance in humans. 2. The follicular epithelial cells synthesize thyroid hormones by incorporating iodine into the amino acid tyrosine on the surface of thyroglobulin (Tg), a protein secreted into the colloid of the follicle. o Iodide is a key substrate for thyroid hormone synthesis; a dietary intake in excess of 100μg/day is required to maintain thyroid function in adults. o The thyroid secretes predominantly thyroxine (T4) and only a small amount of triiodothyronine (T3); approximately 85% of (T3) in blood is produced from T4 by a family of monodeiodinase enzymes that are active in many tissues, including liver, muscle, heart and kidney. o T4 has a longer half-life in blood than T3 (approximately 1 week compared with approximately 18 hours), and binds and activates thyroid hormone receptors less effectively than T3. o T3 and T4 circulate in plasma almost entirely (> 99%) bound to transport proteins, mainly thyroxine-binding globulin (TBG). It is the unbound or free hormones that diffuse into tissues and exert diverse metabolic actions. o Production of T3 and T4 in the thyroid is stimulated by thyrotrophin (thyroid-stimulating hormone, TSH), a glycoprotein released from the thyrotroph cells of the anterior pituitary in response to the hypothalamic tripeptide, thyrotrophin-releasing hormone (TRH). o There is a negative feedback of thyroid hormones on the hypothalamus and pituitary such that in thyrotoxicosis, when plasma concentrations of T3 and T4 are raised, TSH secretion is suppressed. o TSH is usually regarded as the most useful investigation of thyroid function. 1 ENDOCRINOLOGY Thyroid Gland Diseases Investigations in patient with thyroid diseases: 1. Thyroid function tests - T3, T4 and TSH. 2. Thyroid Autoantibodies. 3. Imaging (Ultrasound, CT scan , PET scan …etc) 4. Thyroid scan and radioactive iodine uptake: Radioactive iodine uptake (RAIU) is a measure of iodine uptake by the thyroid over a pre-specified time frame, typically 24 hours. RAIU is used to evaluate the cause of hyperthyroidism; it is not indicated in patients with normal or elevated TSH levels. RAIU percentage is typically very high in patients with Graves’s disease (diffusely increased uptake) and only moderately elevated in those with toxic nodule or toxic multinodular goiter. 5. Tissue biopsy (histopathological examination). Interpretation of thyroid function test TSH T4 T3 Interpretation U.D Raised Raised Primary thyrotoxicosis U.D Normal Raised Primary T3 toxicosis Normal or Raised Raised Secondary thyrotoxicosis raise Non adherence to medications U.D Normal Normal Subclinical thyrotoxicosis Elevated Low Low Primary hypothyroidism Normal / Low Low Low Secondary hypothyroidism Elevated Normal Normal Subclinical hypothyroidism The percentage of thyroid autoantibodies in different populations Antithyriod peroxidase Anti-TSH General population 8 - 27 0 Grave’s disease 50 -80 80 - 95 Autoimmune hypothyroidism 90 - 100 10 – 20 2 ENDOCRINOLOGY Thyroid Gland Diseases Functional Thyroid Disorders THYROTOXICOSIS: o Thyrotoxicosis is a term used to describe thyroid hormone excess from all sources, whereas hyperthyroidism is the more specific term to describe thyroid gland overactivity. o Thyrotoxicosis may result from endogenous thyroid disorders, pituitary tumors, and exogenous levothyroxine. o The most common causes of hyperthyroidism are Graves’s disease. o Causes of thyrotoxicosis and their relative frequency are: Cause Frequency (%) Grave’s disease 76 Multinodular goitre 14 Solitary thyroid adenoma 5 Thyroiditis Subacute (de Quervain’s 3 Post-partum 0.5 Iodide-induced Drugs (amiodarone) 1 Radiographic contrast media - Iodine supplementation programme - Extrathyroidal source of thyroid hormone Factitious thyrotoxicosis 0.2 Struma ovarii - TSH-induced TSH-secreting pituitary adenoma 0.2 Choriocarcinoma and hydatidiform mole - Follicular carcinoma and or metastasis 0.1 3 ENDOCRINOLOGY Thyroid Gland Diseases Clinical features of Thyrotoxicosis: 1 Only in Grave’s 2 commonly in elderly 3 rarely seen Symptoms Signs General Weight loss despite normal or increased Weight loss appetite Goiter with bruit 1 Heat intolerance Fatigue, apathy2 Osteoporosis (fracture, loss of height) Gastrointestinal Diarrhoea, steatorrhoea, hyperdefecation Anorexia2 Vomiting3 Cardiorespiratory Palpitations Sinus tachycardia Dyspnoea on exertion Atrial fibrillation Angina Systolic hypertension/ Ankle swelling increased pulse pressure Exacerbation of asthma3 Cardiac failure Haematological Lymphadenopathy3 Neuromuscular Anxiety, irritability, emotional lability, Tremor psychosis Hyper-reflexia Tremor Ill-sustained clonus Muscle weakness Proximal myopathy Periodic paralysis (predominantly in Chinese) Bulbar myopathy2 Dermatological Sweating Palmar erythema Pruritis Pretibial myxoedema1 Alopecia Finger clubbing (thyroid acropachy)1 Spider naevi3 Onycholysis3 Pigmentation3 Vitiligo1 Reproductive Amenorrhoea/oligomenorrhoea Gynaecomastia Infertility, spontaneous abortion Loss of libido, impotence Ocular Grittiness, red eyes Lid retraction, lid lag Excessive lacrimation Chemosis1 Diplopia1 Exophthalmos1 Loss of acuity1 Periorbital oedema1 Corneal ulceration1 Ophthalmoplegia1 4 ENDOCRINOLOGY Thyroid Gland Diseases Investigations: The first-line investigations are serum T3, T4 and TSH.  The typical pattern of hyperthyroidism is TSH suppression with an elevated T4 and/or T3.  A normal serum TSH in the setting of an elevated T4 and/or T3 concentration suggests the presence of a TSH-secreting pituitary adenoma. When biochemical thyrotoxicosis has been confirmed, further investigations should be undertaken to determine the underlying cause, including measurement of TSH receptor antibodies (TRAb, elevated in Graves’ disease) and radioisotope scanning. Management: Rapid control of adrenergic symptoms with a β-blocker is indicated in most patients with thyrotoxicosis. Beta-blockers should not be used for long-term treatment of thyrotoxicosis but are extremely useful in the short term. (Propranolol, Nadolol, Atenolol) Although the specific intervention used is usually determined by the underlying cause and patient and physician preference, control of the thyrotoxic state may be achieved by one of three treatment modalities: thionamides, radioactive iodine ablation, or surgery. I. Thionamides (Carbimazole/Methimazole and propylthiouracil): o These drugs reduce the synthesis of new thyroid hormones by inhibiting the iodination of tyrosine. Also they have immune modulating effects. o Thionamides may be used to prepare patients for thyroidectomy or radioiodine treatment, or they may be used as the primary therapy. o Usually, these drug results in subjective improvement within 10–14 days and renders the patient clinically and biochemically euthyroid at 6–8 weeks. o In most patients, these drugs should continue for 12–18 months. o Adverse effects of antithyroid medications:  The most common is a rash.  Agranulocytosis is a rare but potentially serious complication that cannot be predicted by routine measurement of white blood cell count but which is reversible on stopping treatment. Patients should be warned to stop the drug and seek medical 5 ENDOCRINOLOGY Thyroid Gland Diseases advice immediately, whenever a severe sore throat or fever develop while on treatment.  PTU is associated with a small but definite risk of hepatotoxicity, which, in some instances, has resulted in liver failure requiring liver transplantation, and even in death. It should therefore be considered second-line therapy to carbimazole and be used only during pregnancy or breastfeeding, or if an adverse reaction to carbimazole has occurred. II. Radioactive iodine ablation  131I is administered orally as a single dose and is trapped and organified in the thyroid. Although it decays within a few weeks, it has long-lasting inhibitory effects on survival and replication of follicular cells.  It is effective in 75-90% of patients within 4–12 weeks. During the lag period, symptoms can be controlled by a β-blocker or, in more severe cases, by carbimazole. If thyrotoxicosis persists after 6 months, a further dose of 131I can be given.  The disadvantage of 131I treatment is that the majority of patients eventually develop hypothyroidism.  In a patient with severe thyrotoxicosis, radioactive iodine may provide additional substrate to the hyperfunctioning gland, resulting in exacerbation of the hyperthyroid state. Consequently, it may be reasonable to initiate a thionamide prior to ablation to lower the thyroid hormone levels.  131I is usually avoided in patients with Graves’ ophthalmopathy and evidence of significant active orbital inflammation.  In women of reproductive age, pregnancy must be excluded before administration of 131I and avoided for 6 months thereafter; men are also advised against fathering children for 6 months after receiving 131I. III. Surgery:  Surgery is rarely first-line therapy, given the inherent risks with any surgery. Patients in whom control cannot be achieved with thionamides and those who are not comfortable with radioiodine therapy are typically referred for surgery.  Restoration of the euthyroid state before surgery with thionamides is important to improve hemodynamics during general anesthesia and decrease the patient's risk of thyroid storm. 6 ENDOCRINOLOGY Thyroid Gland Diseases Grave’s disease: o Is a multiorgan system autoimmune disorder that can affect the thyroid, eyes, and skin. o It is frequently seen in women between the ages of 20 and 50 years and is the most common cause of hyperthyroidism worldwide. o Antibodies against the TSH receptor stimulate autonomous production of T4 and T3. o Features specific for Grave’s disease: 1. Goiter with bruit. 2. Thyroid acropachy. 3. Pretibial myxedema. 4. Thyroid ophthalmopathy. o Thyroid stimulating antibodies are usually positive and RAIU and scan will show markedly increased uptake with diffuse activity on the scan. o Because thionamide drugs also have an immunomodulatory effect that reduces autoantibody titers, antithyroid drugs are often first-line treatment for Graves’s disease. o If the patient does not go into remission or if disease recurs, definitive therapy with radioactive iodine ablation or surgery is recommended. Toxic adenomaand Multinodular Goiter:  Activating mutations in the TSH receptor gene are responsible for the autonomous production of thyroid hormone.  They can be relatively asymptomatic or with mild symptom.  Because of the loss of normal regulation of thyroid hormone production, patients are at risk for developing acute thyrotoxicosis when exposed to iodine excess, particularly after a contrast load for medical testing (Jod-Basedow phenomenon), such as in cardiac catheterization and contrast-enhanced CT scans.  On physical examination, a nodule(s) may be palpable or there may be a diffusely enlarged goiter with a nodular contour but no discrete palpable nodules.  The thyroid uptake scan will reveal increased activity in the “hot” nodule(s) with relative suppression of the remaining thyroid tissue. These results should then be correlated with the ultrasonographic findings to determine if any additional nodules exist, which will require further investigation with FNA. 7 ENDOCRINOLOGY Thyroid Gland Diseases  Radioactive iodine ablation or surgery is the most common treatment for toxic nodules.If a patient has a particularly large goiter with compressive symptoms or if there is concern for malignancy, surgery is recommended as first-line therapy.  Thionamides are recommended to normalize thyroid hormone levels prior to radioactive iodine or surgery; this is done to avoid exacerbation of the thyrotoxicosis. Factitious thyrotoxicosis: o Cause by exogenous thyroxine intake which suppresses pituitary TSH secretion and hence iodine uptake. o Characterized by: 1. Negligible iodine uptake. 2. Low or undetectable thyroglobulin level. 3. High T4:T3 ratio more than 70:1 (typically 30:1) Subclinical Hyperthyroidism:  Subclinical hyperthyroidism is a laboratory-based diagnosis, defined as suppressed TSH level with normal T3 and T4 levels.  Symptoms are typically mild; most patients are asymptomatic.  Repeat assessment of thyroid function should be performed 6 to 12 weeks after the initial tests, as the values will normalize in up to 30% of patients.  Treatment is recommended for patients with a TSH level below 0.1μU/mL (0.1mU/L).  Treatment either radioactive iodine or thionamide. Destructive Thyroiditis: o Thyroiditis is a self-limited inflammatory condition of the thyroid resulting in the release of preformed thyroid hormone into the circulation. o There are two categories of thyroiditis: painful and painless. 1. The causes of painful thyroiditis are inflammatory (de Quervain or subacute granulomatous thyroiditis), infectious (suppurative), and radiation-induced. 8 ENDOCRINOLOGY Thyroid Gland Diseases 2. Painless thyroiditis is more commonly seen than painful thyroiditis and has several causes, including postpartum thyroiditis, silent thyroiditis, and drug-induced thyroiditis. o The disease course has two phases: thyrotoxic and recovery phase. The duration of the thyrotoxicphase is typically 2 to 6 weeks, during which patients may exhibit classic symptoms of thyrotoxicosis. Following the release of preformed hormone, the damaged thyroid ceases production of T3 and T4 during the recovery phase; consequently, administration of thionamides will not be effective in treating elevated hormone levels. The patient may then become clinically hypothyroid, a condition that may require temporary levothyroxine therapy. The length of the hypothyroid phase can vary but classically is 6 to 12 weeks. Subacute (de Quervain’s) thyroiditis: o In its classical painful form, subacute thyroiditis is a transient inflammation of the thyroid gland occurring after infection with Coxsackie, mumps or adenoviruses. The condition can also be precipitated by drugs, including interferon-α and lithium. o There is pain in the region of the thyroid that may radiate to the angle of the jaw and the ears, and is made worse by swallowing, coughing and movement of the neck. o The thyroid is usually palpably enlarged and tender. o In the thyrotoxic phase, the iodine uptake is low,and the erythrocyte sedimentation rate (ESR) is usually raised. o The pain and systemic upset usually respond to simple measures such NSAIDs. Occasionally, however, it may be necessary to prescribe prednisolone 40 mg daily for 3–4 weeks in severe cases. o The thyrotoxicosis is mild and treatment with a β-blocker is usually adequate. Antithyroid drugs are of no benefit because thyroid hormone synthesis is impaired rather than enhanced. o Careful monitoring of thyroid function and symptoms is required so that levothyroxine can be prescribed temporarily in the hypothyroid phase. 9 ENDOCRINOLOGY Thyroid Gland Diseases Post-partum thyroiditis:  The maternal immune response, which is modified during pregnancy to allow survival of the fetus, is enhanced after delivery and may unmask previously unrecognised subclinical autoimmune thyroid disease.  Occur in 5-10% of women within 6 months of delivery. Those affected are likelyto have antithyroid peroxidase Ab in the serum  Symptomatic thyrotoxicosis presenting for the first time within 12 months of childbirth is likely to be due to post-partum thyroiditis and the diagnosis is confirmed by a negligible radio-isotope uptake.  Post-partum thyroiditis tends to recur after subsequent pregnancies, and eventually patients progress over a period of years to permanent hypothyroidism. Thyroid storm: o This is a rare but life-threatening complication of thyrotoxicosis. It is a medical emergency and has a mortality of 10% despite early recognition and treatment. o Although thyroid storm has been reported with many causes of thyrotoxicosis, it occurs most commonly with Graves’s disease. o It is most commonly precipitated by infection, surgery, myocardial infarction or within a few days of 131I therapy. o The most prominent signs are fever, agitation, delirium, nausea, vomiting diarrhea, jaundice, tachycardia or atrial fibrillation and, in the older patient, cardiac failure. o The diagnosis is based on clinical presentation but can generally be ruled out if T4 and T3 levels are within normal limits. o Treatment:  Rehydration and Antipyretic.  Propranolol, either orally (80 mg 4 times daily) or intravenously (1– 5 mg 4 times daily).  PTU are preferred agents because it has added benefit of blocking peripheral conversion of T4 to T3, carbimazole is alternative.  Dexamethasone (2 mg 4 times daily).  Iodine drops (potassium iodide or Lugol’s Solution) should be administered to inhibit further release of T4,T3 from the gland.  Searching for and treating precipitating factors. Atrial fibrillation in thyrotoxicosis: 10 ENDOCRINOLOGY Thyroid Gland Diseases o Atrial fibrillation occurs in about 10% of patients with thyrotoxicosis. o The incidence increases with age. o Characteristically, the ventricular rate is little influenced by digoxin but responds to the addition of a β-blocker. o Thromboembolic vascular complications are particularly common in thyrotoxic AF, so, anticoagulation is required, unless contraindicated. o Once the patient is euthyroid (treated), 50% will revert to sinus rhythm spontaneously, the remainder may require cardioversion. HYPOTHYROIDISM: o Hypothyroidism refers to low circulating thyroid hormone levels. o Women affected approximately six times more frequently than men. o Autoimmune disease (Hashimoto’s thyroiditis) and thyroid failure following 131I or surgical treatment of thyrotoxicosis account for over 90% of cases, except in areas where iodine deficiency is endemic. o Etiology: 1. Autoimmune:  Hashimoto’s thyroiditis,  Spontaneous atrophic hypothyroidism,  Graves’ disease with TSH receptor blocking antibodies. 2. Iatrogenic: Radioactive iodine, Thyroidectomy, Drug: (amiodarone, lithium) 3. Transient thyroiditis 4. Iodine deficiency 5. Congenital: dyshormonogenesis 6. Infiltrative: Amyloidosis, Sarcoidosis, Riedel’s Thyroiditis 7. Secondary hypothyroidism o Evaluation:  An elevated serum TSH and low T4 level indicates the diagnosis of primary hypothyroidism.  Measurements of serum T3 are unhelpful since they do not discriminate reliably between euthyroidism and hypothyroidism.  The presence of TPO antibodies suggests that Hashimoto thyroiditis is the underlying cause.  Thyroid imaging is not indicated unless there is concern for a nodule on physical examination.  Non specific laboratory investigations include anemia, hypercholesterolemia, and hyponatremia. 11 ENDOCRINOLOGY Thyroid Gland Diseases o Clinical features of hypothyroidism: 3 for rare Symptoms Signs General Weight gain Weight gain Cold intolerance Hoarse voice Fatigue, somnolence Goitre Hoarseness Gastrointestinal Constipation Ileus3 Ascites3 Cardiorespiratory Bradycardia Hypertension Pericardial and pleural effusions3 Haematological Macrocytosis Anaemia Iron deficiency (pre-menopausal women) Normochromic Neuromuscular Carpal tunnel syndrome Delayed relaxation of tendon reflexes Aches and pains Cerebellar ataxia3 Muscle stiffness Myotonia3 Deafness Depression Psychosis (myxoedema madness)3 Dermatological Dry skin Myxoedema Dry hair Purplish lips Alopecia Malar flush Carotenaemia Vitiligo Erythema ab igne (Granny's tartan) Reproductive Menorrhagia Infertility Galactorrhoea3 Impotence3 Ocular Periorbital oedema/myxoedema Loss of lateral eyebrows Management: 12 ENDOCRINOLOGY Thyroid Gland Diseases o Thyroid hormone replacement with levothyroxine alone is recommended. The goal of therapy is normalization of the TSH. o The starting dose can be weight-based at 1.67μg/kg/d, using ideal body weight. In patients with prevalent cardiac disease, tachyarrhythmias, or multiple comorbidities, or in those who are older than 65 years, the dose should not be based on weight but rather should be 25 to 50μg/d. o The dose should be titrated based on TSH levels measured 6 to 8 weeks after any dose change. o To improve gastrointestinal absorption, levothyroxine should be taken on an empty stomach, 1 hour before or 2 to 3 hours after ingestion of food or medications that would interfere with absorption, such as calcium- or iron-containing supplements. o Patients with celiac disease may require higher levothyroxine doses because of impaired absorption. o Patients feel better within 2–3 weeks. Reduction in weight and periorbital puffiness occurs quickly but the restoration of skin and hair texture and resolution of any effusions may take 3–6 months. Levothyroxine replacement in ischaemic heart disease:  Exacerbation of myocardial ischaemia, infarction and sudden death are recognised complications of levothyroxine replacement, even using doses as low as 25 μg per day.  In patients with known ischaemic heart disease, thyroid hormonereplacement should be introduced at low dose and increased very slowly under specialist supervision.  Coronary intervention may be required if angina is exacerbated by levothyroxine replacement therapy. Hashimoto’s thyroiditis: 13 ENDOCRINOLOGY Thyroid Gland Diseases  It is characterised by destructive lymphoid infiltration of the thyroid, ultimately leading to a varying degree of fibrosis and goitre.  Hashimoto’s thyroiditis increases in incidence with age, and it is more common in women than in men (4:1).  Many present with a small or moderately sized diffuse goitre, which is characteristically firm or rubbery in consistency.  Around 25% of patients are hypothyroid at presentation. In the remainder, serum T4 is normal and TSH normal or raised, but these patients are at risk of developing overt hypothyroidism in future years.  Antithyroid peroxidase antibodies are present in the serum in more than 90% of patients with Hashimoto’s thyroiditis.  Levothyroxine therapy is indicated as treatment for hypothyroidismin a dose sufficient to suppress serum TSH to low but detectable levels.  There is an increased risk of thyroid lymphoma, although this is exceedingly rare. Myxedema Coma: o An extreme but rare manifestation of hypothyroidism, resulting in life- threatening secondary systemic decompensation. o The mortality rate is 50% and survival depends on early recognition and treatment of hypothyroidism and the triggering factors. o Myxedema coma is more common in elderly women; it may occur in those with a history of hypothyroidism or no antecedent illness. o Precipitating events include myocardial infarction, infection, stroke, trauma, gastrointestinal bleeding, or metabolic derangements. o Mental status changes and hypothermia are the most common clinical manifestations. The spectrum of mental status changes includes lethargy, stupor, coma, depression, or even psychosis. Hypothermia (temperature less than 34.4 °C) is present in nearly all patients; lower temperatures are associated with a worse prognosis. Ventilatory drive is decreased, resulting in hypoxemia and hypercapnia. Additional signs include bradycardia, hypoglycemia, hyponatremia, and/or hypotension. A significant percentage of patients experience seizures, which may be related to the coexisting metabolic derangements. o Diagnosis is made based on the clinical presentation and the coexisting metabolic abnormalities (hypoglycemia, hyponatremia).If is suspected, the serum TSH and T4 levels should be tested immediately. The serum cortisol level should be checked as soon as possible to 14 ENDOCRINOLOGY Thyroid Gland Diseases evaluate for concomitant adrenal insufficiency prior to initiation of thyroid hormone replacement. o Management:  Empirically initiate high-dose glucocorticoid therapy.  Supportive care (mechanical ventilation, vasopressors, warmed intravenous fluids, warming blankets, and management of the underlying precipitating event).  Intravenous levothyroxine should be administered, initially as an intravenous bolus of 200 to 500 μg, followed by daily doses of 50 to 100 μg intravenously until transition to an oral formulation is feasible. Treatment with intravenous T3 is alternative. Euthyroid Sick Syndrome (Nonthyroidal illness syndrome): o Changes seen in thyroid function test results during critical illness. o The typical pattern is initially a low T3 level, followed by a decline in the T4 level. As the patient becomes more critically ill, the TSH level may also decline, creating a clinical picture that is difficult to discern from central hypothyroidism. o If the TSH is greater than 20μU/mL (20mU/L) or is undetectable, ESS is less likely to be the cause and overt thyroid dysfunction should be strongly considered. o In a clinically euthyroid patient, thyroid function tests should be repeated 6 weeks after hospitalization. Amiodarone and thyroid disease:  The anti-arrhythmic agent amiodarone has a structure that is analogous to that of T4and contains huge amounts of iodine; a 200 mg dose contains 75 mg iodine.  Amiodarone also has a cytotoxic effect on thyroid follicular cells and inhibits conversion of T4 to T3.  20% of patient receiving amiodarone will develop hypothyroidism or thyrotoxicosis, and so thyroid function should be monitored regularly.  The Thyrotoxicosis can be classified as either: Type I: iodine-induced excess thyroid hormone synthesis inpatients with an underlying thyroid disorder, such asnodular goitre or latent Graves’ disease (an example of the Jod–Basedow effect). 15 ENDOCRINOLOGY Thyroid Gland Diseases Type II: thyroiditis due to a direct cytotoxic effect of amiodarone administration.  Antithyroid drugs may be effective in patients with the type I form but are ineffective in type II thyrotoxicosis. Prednisolone is beneficial in the type II form.If the cardiac state allows, amiodarone should be discontinued,  Hypothyroidism should be treated with levothyroxine, which can be given while amiodarone is continued. Thyroid Diseases and Pregnancy:  Increased estrogen levels during pregnancy cause a rise in thyroxine- binding globulin. To maintain a stable free T4 and T3, thyroid hormone production is increased and TSH remains within the normal range.  Routine screening of TSH is not indicated for every pregnant woman. TSH screening is indicated in women with a risk of thyroid gland dysfunction, including known thyroid disease; those with autoimmune disorders, goiter, previous head/neck irradiation, previous thyroid surgery, known positive TPO antibodies or positive TSI antibodies, or a strong family history of thyroid dysfunction; those who live in iodine- deficient areas; or those older than 30 years.  Fetal thyroid tissue is not functional until 10 to 12 weeks' gestation, necessitating maternal thyroid hormone transfer through the placenta.  Thyroid hormone deficiency can negatively affect fetal neurocognitive development.It is critical to maintain a euthyroid state during pregnancy in these patients.  TSH testing should be performed every 6 weeks throughout pregnancy, with adjustments in thyroid hormone replacement dosing as needed to maintain the TSH within the trimester-specific normal range. The largest dose escalations typically occur in the first trimester, with more dose stability later in pregnancy.  In patients on levothyroxine replacement, the dose of the medication may need to be increased, on average by 30% to 50%.  PTU is the preferred antithyroid drug during the first trimester because of potential teratogenic effects from methimazole during organogenesis.  Radioiodine therapy is contraindicated during pregnancy and while breastfeeding. 16 ENDOCRINOLOGY Thyroid Gland Diseases Structural Disorders of the Thyroid Gland Thyroid nodule: o Nodularity of the thyroid is extremely common, the prevalence increases with age. In autopsy series and screening ultrasound studies, nodules may be seen in up to 60%. o Nodules are frequently detected incidentally on imaging studies performed for other reasons. o Most thyroid nodules are benign, with only approximately 10% harboring a malignancy (primary or metastatic). o A careful history should be performed in patients with a thyroid nodule. Focusing on history of radiation exposure, family history of thyroid cancer, or a personal history of thyroid cancer, rapid nodule growth, and hoarseness.Pain is an uncommon finding with thyroid nodules, but when present it is usually associated with benign conditions. o On examination, if the nodule is hard, fixed to surrounding tissue (nonmobile with swallowing), and/or there is associated cervical lymphadenopathy; the risk of malignancy is greater. o TSH measurement is the initial test in a patient with a thyroid nodule.If the TSH is suppressed, measurement of T4 and T3 should be performed, and a radionuclide scan should be considered.  If the scan identify “hot” or functioning nodules, it has a very low likelihood of malignancy and typically do not require FNA.  If the scan show “cold” or non-functioning nodules, OR the patient has normal/elevated TSH, the ultrasound and FNA is indicated. o Ultrasonic features concerning for malignancy include microcalcifications, marked hypoechogenicity, irregular borders. These findings are nearly 70% specific for cancer. o Malignant nodules and those that are suspicious for malignancy require prompt excision. 17 ENDOCRINOLOGY Thyroid Gland Diseases Multinodular (Nontoxic) goiters: o Occur more frequently with advancing age, low iodine intake, or Hashimoto disease. o The risk for malignancy is the same for multiple nodules as it is for a solitary nodule; therefore, the evaluation and management are identical. Biopsy should be performed on the three or four nodules (larger than 1 cm) with the most suspicious ultrasound features. o Levothyroxine therapy to suppress TSH secretion and reduce goiter size is generally not helpful, poses a risk of thyrotoxicosis, and is not recommended. Radioactive iodine ablation is not an option for euthyroid and hypothyroid patients. o Surgical removal is the treatment of choice if the compressive symptoms are significant, if malignancy is suspected, or if the patient desires cosmetic intervention. 18 ENDOCRINOLOGY Thyroid Gland Diseases Thyroid Cancer: o The vast majority of patients with thyroid cancer have well- differentiated (papillary or follicular) thyroid cancer, with excellent long-term survival. o Treatment of well-differentiated cancer includes a combination of surgery, radioactive iodine, and levothyroxine suppression. o Anaplastic thyroid cancer is undifferentiated and is the most aggressive form of thyroid cancer.Patients are usually over 60 years of age and present with rapid thyroid enlargement over 2–3 months. The goitre is hard and there may be stridor due to tracheal compression and hoarseness due to recurrent laryngeal nerve palsy. o There is no effective treatment for anaplastic carcinoma, although surgery and radiotherapy may be considered in some circumstances. o The prognosis for lymphoma, which may arise from preexisting Hashimoto’s thyroiditis, is better. Treatment is with combination chemotherapy and external beam radiotherapy. o Medullary thyroid cancer represents less than 10% of all thyroid cancers. Approximately 25% of medullary thyroid cancers are 19 ENDOCRINOLOGY Thyroid Gland Diseases hereditary or associated with hereditary condition like multiple endocrine neoplasia type 2A (MEN-2A), MEN2B. o All patients with medullary thyroid cancer should be screened with RET proto-oncogene sequencing. o Screening for pheochromocytoma with measurement of plasma fractionated metanephrine levels should be done in all patients with an RET mutation prior to thyroidectomy. 20