Presentation on theme: "Thyroid Disorders Dr Muries Barham ENDOCRINOLOGEST."— Presentation transcript:
Thyroid Disorders Dr Muries Barham ENDOCRINOLOGEST
Thyroid Disorders Anatomy The thyroid gland consists of two lateral lobes connected by an isthmus. It is closely attached to the thyroid cartilage and to the upper end of the trachea, and thus moves on swallowing.It is often palpable in normal women.
The normal thyroid is 12–20 g in size, highly vascular, and soft in consistency. Four parathyroid glands, which produce PTH,are located posterior to each pole of the thyroid. The recurrent laryngeal nerves traverse the lateral borders of the thyroid gland and must be identified during thyroid surgery to avoid injury and vocal cord paralysis.
The thyroid axis is a classic example of an endocrine feedback loop. Hypothalamic TRH stimulates pituitary production of TSH, which, in turn, stimulates thyroid hormone synthesis and secretion.
Thyroid hormones, acting predominantly through thyroid hormone receptor 2 (TR2), feed back to inhibit TRH and TSH production. The "set-point" in this axis is established by TSH.
TRH is the major positive regulator of TSH synthesis and secretion. Peak TSH secretion occurs 15 min after administration of exogenous TRH. Dopamine, glucocorticoids, and somatostatin suppress TSH but are not of major physiologic importance except when these agents are administered in pharmacologic doses
Thyroid function tests TSH levels can discriminate between hyperthyroidism, hypothyroidism and euthyroidism. There are pitfalls, however. These are mainly with hypopituitarism, with the ‘sick euthyroid’ syndrome, all of which may give ‘false’,low results implying hyperthyroidism.
As a single test of thyroid function it is the most sensitive in most circumstances, but accurate diagnosis requires at least two tests – for example, TSH plus free T4 or free T3 where hyperthyroidism is suspected, TSH plus serum free T4 where hypothyroidism is likely
Causes of Hypothyroidism Primary Autoimmune hypothyroidism: Hashimoto's thyroiditis, atrophic thyroiditis Iatrogenic: 131 I treatment, subtotal or total thyroidectomy, external irradiation of neck for lymphoma or cancer Drugs: iodine excess (including iodine-containing contrast media and amiodarone), lithium, antithyroid drugs, p-aminosalicylic acid, interferon- and other cytokines, aminoglutethimide, sunitinib Congenital hypothyroidism: absent or ectopic thyroid gland, dyshormonogenesis, TSH-R mutation
Causes of Hypothyroidism Iodine deficiency Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedel's thyroiditis Transient -Silent thyroiditis, including postpartum thyroiditis,Subacute thyroiditis -Withdrawal of thyroxine treatment in individuals with an intact thyroid - After 131 I treatment or subtotal thyroidectomy for Graves' disease
Causes of Hypothyroidism Secondary -Hypopituitarism: tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehan's syndrome, trauma, genetic forms of combined pituitary hormone deficiencies -Isolated TSH deficiency or inactivity -Hypothalamic disease: tumors, trauma, infiltrative disorders, idiopathic
Essentials of Diagnosis Symptoms Tiredness, weakness Dry skin Feeling cold Hair loss Difficulty concentrating and poor memory Constipation Weight gain with poor appetite Dyspnea Hoarse voice Menorrhagia (later oligomenorrhea or amenorrhea) Paresthesia Impaired hearing
Atrophic (autoimmune) hypothyroidism. This is the most common cause of hypothyroidism and is associated with antithyroid autoantibodies leading to lymphoid infiltration of the gland and eventual atrophy and fibrosis. It is six times more common in females and the incidence increases with age. The condition is associated with other autoimmune disease such as pernicious anaemia, vitiligo and other endocrine deficiencies. In some instances intermittent hypothyroidism occurs with recovery from disease; antibodies which block the TSH receptor may sometimes be involved in the aetiology.
Hashimoto’s thyroiditis This form of autoimmune thyroiditis,again more common in women and most common in late middle age, produces atrophic changes with regeneration,leading to goitre formation. The gland is usually firm and rubbery but may range from soft to hard.
Hashimoto’s thyroiditis TPO antibodies are present, often in very high titres (> 1000 IU/L). Patients may be hypothyroid or euthyroid, though they may go through an initial toxic phase, ‘Hashi-toxicity’. Levothyroxine therapy may shrink the goitre even when the patient is not hypothyroid.
Postpartum thyroiditis This is usually a transient phenomenon observed following pregnancy. It may cause hyperthyroidism, hypothyroidism or the two sequentially. It is believed to result from the modifications to the immune system necessary in pregnancy, and histologically is a lymphocytic thyroiditis.
Postpartum thyroiditis The process is normally self-limiting, but when conventional antibodies are found there is a high chance of this proceeding to permanent hypothyroidism. Postpartum thyroiditis may be misdiagnosed as postnatal depression
Subacute Thyroiditis Subacute thyroiditis(de Quervain's Thyroiditis; Giant Cell Thyroiditis; Granulomatous Thyroiditis) is an acute inflammatory disease of the thyroid probably caused by a virus. Symptoms include fever and thyroid tenderness. Initial hyperthyroidism is common, sometimes followed by a transient period of hypothyroidism
Subacute Thyroiditis History of an antecedent viral URI is common. Diagnosis is clinical and with thyroid function tests. Treatment is with high doses of NSAIDs or with corticosteroids. The disease usually resolves spontaneously within months.
Subacute Thyroiditis Symptoms and Signs There is pain in the anterior neck and fever of 37.8° to 38.3° C. Neck pain characteristically shifts from side to side and may settle in one area, frequently radiating to the jaw and ears.
Defects of hormone synthesis Iodine deficiency. Dietary iodine deficiency still exists in some areas. The patients may be euthyroid or hypothyroid depending on the severity of iodine deficiency Dyshormonogenesis. This rare condition is due to genetic defects in the synthesis of thyroid hormones; patients develop hypothyroidism with a goitre.
Myxedema Coma uncommon but life-threatening form of untreated hypothyroidism. The condition occurs in patients with long-standing, untreated hypothyroidism.
Myx. Coma-Precipitating factors CNS depressants(barbiturates, phenothiazines, narcotics, anaesthetics) Infections Trauma Hypothermia Hypoventilation Old age
Hypothyroidism & Myxedema Coma Myxedema Coma Findings: – Decrease mental status – from baseline – Hypothermia/ Hypoglycemia/ Hyponatremia – Bradycardia(soft distant heart sounds,enlarged heart with or without pericardial effusion). – Hypoventillation – Peri-orbital edema – Non-pitting Edema – Delayed Tendon Reflexes
Management of Myxedema ICU admission may be required for ventilatory support and IV medications levothyroxine intravenously (myxedema itself can interfere with levothyroxine's intestinal absorption). – Loading dose of 300 – 400 μg – Then 50 μg daily
The hypothermic patient is warmed only with blankets, since faster warming can precipitate cardiovascular collapse. Patients with hypercapnia require intubation and assisted mechanical ventilation. Infections must be detected and treated aggressively.
Management of Myxedema Electrolytes – Hypertonic saline or IV glucose may be needed if there is severe hyponatremia or hypoglycemia; hypotonic IV fluids should be avoided because they may exacerbate water retention secondary to reduced renal perfusion and inappropriate vasopressin secretion Avoid sedation
Prognosis of Myxedema Glucocorticoids - Parenteral hydrocortisone (50 mg every 6 h) should be administered, because there is impaired adrenal reserve in profound hypothyroidism.for 1 week, then taper. Mortality is 20%, and is mostly due to underlying and precipitating diseases
Before therapy with thyroid hormone is commenced, the hypothyroid patient requires at least a clinical assessment for adrenal insufficiency, for which the patient would require evaluation and concurrent treatment.
Thyrotoxicosis Thyrotoxicosis is defined as the state of thyroid hormone excess and is not synonymous with hyperthyroidism, which is the result of excessive thyroid function.
Causes of Thyrotoxicosis Primary hyperthyroidism 1-Graves' disease 2-Toxic multinodular goiter 3-Toxic adenoma Functioning thyroid carcinoma metastases 4- Activating mutation of the TSH receptor 5- Activating mutation of G s (McCune-Albright syndrome) 6-Struma ovarii 7-Drugs: iodine excess (Jod-Basedow phenomenon)
Thyrotoxicosis without hyperthyroidism Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue
Secondary hyperthyroidism TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis Chorionic gonadotropin-secreting tumors Gestational thyrotoxicosis
Graves' Disease Graves' disease accounts for 60–80% of thyrotoxicosis. The prevalence varies among populations, reflecting genetic factors and iodine intake (high iodine intake is associated with an increased prevalence of Graves' disease).
Graves' disease occurs in up to 2% of women but is one-tenth as frequent in men. The disorder rarely begins before adolescence and typically occurs between 20 and 50 years of age; it also occurs in the elderly.
Graves' disease is currently viewed as an autoimmune disease of unknown cause. There is a strong familial predisposition in that about 15% of patients with Graves' disease have a close relative with the same disorder, and about 50% of relatives of patients with Graves' disease have circulating thyroid autoantibodies.
. Proposed environmental triggers include stress, tobacco use, infection, and iodine exposure. The postpartum state, which may be associated with heightened immune function, also may trigger the development of Graves' disease in genetically susceptible women.
Symptoms Hyperactivity, irritability, dysphoria Heat intolerance and sweating Palpitations Fatigue and weakness Weight loss with increased appetite Diarrhea Polyuria Oligomenorrhea, loss of libido
Signs Tachycardia; atrial fibrillation in the elderly Tremor Goiter Warm, moist skin Muscle weakness, proximal myopathy Lid retraction or lag Gynecomastia ophthalmopathy and dermopathy
Graves' disease is caused by an autoantibody against the thyroid receptor for thyroid- stimulating hormone (TSH); unlike most autoantibodies, which are inhibitory, this autoantibody is stimulatory, thus causing continuous synthesis and secretion of excess T 4 and T 3.
Graves' disease (like Hashimoto's thyroiditis) sometimes occurs with other autoimmune disorders, including type 1 diabetes mellitus, vitiligo, premature graying of hair, pernicious anemia, connective tissue diseases, and polyglandular deficiency syndrome.
The pathogenesis of infiltrative ophthalmopathy (responsible for the exophthalmos in Graves' disease) is poorly understood but may result from immunoglobulins directed to specific receptors in the orbital fibroblasts and fat that result in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans
Ophthalmopathy may also occur before the onset of hyperthyroidism or as late as 20 yr afterward and frequently worsens or abates independently of the clinical course of hyperthyroidism.
Treatment: Graves' Disease Graves' disease is treated by reducing thyroid hormone synthesis, using antithyroid drugs, or reducing the amount of thyroid tissue with radioiodine ( 131 I) treatment or by thyroidectomy. Antithyroid drugs are the predominant therapy in many centers in Europe and Japan, whereas radioiodine is more often the first line of treatment in USA. No single approach is optimal and that patients may require multiple treatments to achieve remission.
The common side effects of antithyroid drugs are rash, urticaria, fever, and arthralgia (1–5% of patients). These may resolve spontaneously or after substituting an alternative antithyroid drug.
Rare but major side effects include hepatitis; an SLE-like syndrome; and, most important, agranulocytosis (<1%). It is essential that antithyroid drugs are stopped and not restarted if a patient develops major side effects.
symptoms of possible agranulocytosis (e.g., sore throat, fever, mouth ulcers) and the need to stop treatment pending a complete blood count to confirm that agranulocytosis is not present.
Beta blockers (Propranolol (20–40 mg every 6 h) or longer-acting such as atenolol), may be helpful to control adrenergic symptoms, especially in the early stages before antithyroid drugs take effect. The need for anticoagulation with Warfarin should be considered in all patients with atrial fibrillation.
Radioiodine causes progressive destruction of thyroid cells and can be used as initial treatment or for relapses after a trial of antithyroid drugs. There is a small risk of thyrotoxic crisis after radioiodine, which can be minimized by pretreatment with antithyroid drugs for at least a month before treatment.
Antithyroid drugs should be considered for all elderly patients or for those with cardiac problems to deplete thyroid hormone stores before administration of radioiodine. Carbimazole or methimazole must be stopped at least 2 days before radioiodine administration to achieve optimum iodine uptake.
Thyrotoxic crisis, or thyroid storm Is rare and presents as a life-threatening exacerbation of hyperthyroidism, accompanied by fever, delirium, seizures, coma, vomiting, diarrhea, and jaundice. The mortality rate due to cardiac failure, arrhythmia, or hyperthermia is as high as 30%, even with treatment.
Thyrotoxic crisis is usually precipitated by acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis), surgery (especially on the thyroid), or radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.
Management requires intensive monitoring and supportive care, identification and treatment of the precipitating cause, and measures that reduce thyroid hormone synthesis. Large doses of Antithyroid drugs should be given orally or by nasogastric tube.
One hour after the first dose of antithyroid drug. A saturated solution of potassium iodide (5 drops SSKI every 6 h). Propranolol should also be given to reduce tachycardia and other adrenergic manifestations (40–60 mg PO every 4 h; or 2 mg IV every 4 h). Although other -adrenergic blockers can be used, high doses of propranolol decrease T 4 T 3 conversion, and the doses can be easily adjusted.
Additional therapeutic measures include glucocorticoids (e.g., dexamethasone, 2 mg every 6 h), antibiotics if infection is present, cooling, oxygen, and intravenous fluids.
Subclinical hyperthyroidism Patients with serum TSH < 0.1 mU/L have an increased incidence of atrial fibrillation (particularly elderly patients), reduced bone mineral density, increased fractures, and increased mortality. Patients with serum TSH that is only slightly below normal are less likely to have these features.
Subclinical hyperthyroidism Many patients with subclinical hyperthyroidism are taking L-thyroxine; in these patients, reduction of the dose is the most appropriate management unless therapy is aimed at maintaining a suppressed TSH in patients with thyroid cancer or nodules. The other causes of subclinical hyperthyroidism are the same as those for clinically apparent hyperthyroidism.
Subclinical hyperthyroidism Therapy is indicated for patients with endogenous subclinical hyperthyroidism (serum TSH < 0.1 mU/L), especially those with atrial fibrillation or reduced bone mineral density. The usual treatment is 131 I. In patients with milder symptoms (eg, nervousness), a trial of antithyroid drug therapy is worthwhile.
Subclinical Hypothyroidism Subclinical hypothyroidism is elevated serum TSH in patients with absent or minimal symptoms of hypothyroidism and normal serum levels of free T 4. Subclinical thyroid dysfunction is relatively common; it occurs in more than 15% of elderly women and 10% of elderly men, particularly in those with underlying Hashimoto's thyroiditis.
Subclinical Hypothyroidism In patients with serum TSH > 10 mU/L, there is a high likelihood of progression to overt hypothyroidism with low serum levels of free T 4 in the next 10 yr. These patients are also more likely to have hypercholesterolemia and atherosclerosis. They should be treated with L- thyroxine, even if they are asymptomatic
Subclinical Hypothyroidism For patients with TSH levels between 4.5 and 10 mU/L, a trial of L-thyroxine is reasonable if symptoms of early hypothyroidism (eg, fatigue, depression) are present. L-Thyroxine therapy is also indicated in pregnant women and in women who plan to become pregnant to avoid deleterious effects of hypothyroidism on the pregnancy and fetal development.
Subclinical Hypothyroidism Patients should have annual measurement of serum TSH and free T 4 to assess progress of the condition if untreated or to adjust the L- thyroxine dosage
Approach to the Patient With a Thyroid Nodule Thyroid nodules are common, increasingly so with increasing age. In middle-aged and elderly patients, palpation reveals nodules in about 5%. Results of ultrasonography and autopsy studies suggest that nodules are present in about 50% of adults. Many nodules are found incidentally on thyroid imaging studies done for other disorders.
Etiology Most nodules are benign. Benign causes include hyperplastic colloid goiter, thyroid cysts, thyroiditis, and thyroid adenomas. Malignant causes include thyroid cancers.
Evaluation History: Pain suggests thyroiditis or hemorrhage into a cyst. An asymptomatic nodule may be malignant. Symptoms of hyperthyroidism suggest a hyperfunctioning adenoma or thyroiditis, whereas symptoms of hypothyroidism suggest Hashimoto's thyroiditis.
Risk factors for thyroid cancer History of thyroid irradiation, especially in infancy or childhood Age < 20 yr Male sex Family history of thyroid cancer or multiple endocrine neoplasia A solitary nodule Dysphagia Dysphonia Increasing size (particularly rapid growth or growth while receiving thyroid suppression treatment).
Physical examination: Signs that suggest thyroid cancer include stony hard consistency or fixation to surrounding structures, cervical lymphadenopathy, and hoarseness due to recurrent laryngeal nerve paralysis.
If TSH is suppressed, radioiodine scanning is done. Nodules with increased radionuclide uptake (hot) are seldom malignant. If thyroid function tests do not indicate hyperthyroidism or Hashimoto's thyroiditis, or if nodules are indeterminate or cold, FNA biopsy is done to distinguish benign from malignant nodules.
Ultrasonography is useful in determining the size of the nodule but is rarely diagnostic of cancer.Fine-needle aspiration biopsy is not routinely indicated for nodules < 1 cm on ultrasonography.