Thyroid Gland PDF

Thyroid gland DR AMR ALY ELSHORMILISY ASSISTANT PROFESSOR OF INTERNAL MEDICINE - HELWAN UNIVERSITY MRCP-UK SCE ENDOCRINOLOGY AND DIABETES – UK  In the bloodstream, less than one percent of the circulating T3 and T4 remains unbound. This free T3 and T4 can cr...

Thyroid gland DR AMR ALY ELSHORMILISY ASSISTANT PROFESSOR OF INTERNAL MEDICINE - HELWAN UNIVERSITY MRCP-UK SCE ENDOCRINOLOGY AND DIABETES – UK  In the bloodstream, less than one percent of the circulating T3 and T4 remains unbound. This free T3 and T4 can cross the lipid bilayer of cell membranes and be taken up by cells. The remaining 99 percent of circulating T3 and T4 is bound to specialized transport proteins called thyroxine-binding globulins (TBGs), to albumin, or to other plasma proteins. This “packaging” prevents their free diffusion into body cells. More T4 than T3 is produced, but T4 is converted in some peripheral tissues (liver, kidney and muscle) to the more active and potent T3 by 5′- monodeiodination; an alternative 3′-monodeiodination yields the inactive reverse T3 (rT3). The latter step occurs particularly in severe non-thyroidal illness Control of the hypothalamic–pituitary– thyroid axis Thyrotrophin-releasing hormone (TRH), a peptide produced in the hypothalamus, stimulates the pituitary to secrete thyroid-stimulating hormone (TSH). TSH, in turn, stimulates growth and activity of the thyroid follicular cells. The T3 and T4 subsequently secreted into the circulation by follicular cells exert negative feedback on the hypothalamus and pituitary. Hypothyroidism  Hypothyroidism is common, affecting over 1% of the general population and about 5% of individuals over age 60 years. About 85% of affected individuals are women. Thyroid hormone deficiency affects almost all body func- tions. Maternal hypothyroidism during pregnancy results in off- spring with IQ scores that are an average 7 points lower than those of euthyroid mothers. Congenital hypothyroidism occurs in about 1:4000 births; untreated, it causes cretinism with permanent cognitive impairment  Etiology of primary hypothyroidism Hypothyroidism is a common condition with various causes, but 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.  Hashimoto’s thyroiditis ( chronic lymphocytic thyroiditis) This form of autoimmune thyroiditis is more common in women and is characterised by destructive lymphoid infiltration of the thyroid, ultimately leading to a varying degree of fibrosis and thyroid enlargement where many present with a small or moderately sized diffuse goitre, which is characteristically firm or rubbery in consistency. The goitre may be soft, however, and impossible to differentiate from simple goitre by palpation alone. Most common in late middle age. There is an increased risk of thyroid lymphoma, although this is exceedingly rare.  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. Patients may be hypothyroid or euthyroid, though they may go through an initial toxic phase, ‘Hashi-toxicity’ Thyroiditis is frequently associated with other autoimmune conditions: pernicious anemia, Sjögren syndrome, vitiligo, inflammatory bowel disease and celiac disease. Autoimmune thyroiditis is sometimes associated with other endocrine deficiencies ( e.g., type 1 diabetes mellitus, autoimmune gonadal failure, hypoparathyroidism, and adrenal insufficiency ) as part of autoimmune polyendocrine syndrome type 2 (APS-II).  Postpartum thyroiditis This is usually a transient phenomenon observed following pregnancy (in the first 12 months postpartum) and occasionally after miscarriages. It may cause hyperthyroidism, hypothyroidism or the two sequentially (the thyrotoxic phase typically occurs 2–6 weeks postpartum and lasts 2–3 months). It is believed to result from the modifications to the immune system necessary in pregnancy. The process is normally self-limiting, but when conventional antibodies are found(over 80% have antithyroid antibodies) there is a high chance of this proceeding to permanent hypothyroidism. Postpartum thyroiditis may be misdiagnosed as postnatal depression, emphasizing the need for thyroid function tests in this situation. Postpartum thyroiditis tends to recur after subsequent pregnancies, and eventually patients progress over a period of years to permanent hypothyroidism.  Defects of hormone synthesis Iodine deficiency Dietary iodine deficiency still exists as ‘endemic goitre’ in some areas where goitre is occasionally massive. The patients may be euthyroid or hypothyroid, depending on the severity of iodine deficiency. The mechanism is thought to be borderline hypothyroidism leading to TSH stimulation and thyroid enlargement in the face of continuing iodine deficiency. Efforts to prevent deficiency by providing iodine in salt continue worldwide but often with incomplete success.  Dyshormonogenesis This rare condition is due to genetic defects in the synthesis of thyroid hormones; patients develop hypothyroidism with goitre. One particular familial form is Pendred syndrome which is Autosomal recessive syndrome associated with sensorineural deafness. Clinical picture of hypothyrodism  The clinical presentation depends on the duration and severity of the hypothyroidism. A consequence of prolonged hypothyroidism is the infiltration of many body tissues by the mucopolysaccharides, hyaluronic acid and chondroitin sulphate. Some hypothyroid patients with Hashimoto thyroiditis have symptoms that are not due to hypothyroidism but rather to conditions associated with Hashimoto thyroiditis; these include Addison disease, hypoparathyroidism, diabetes mellitus, pernicious anemia, Sjögren syndrome, vitiligo and celiac disease. Myxoedema madness Depression is common in hypothyroidism. Rarely, with severe hypothyroidism in the elderly, the patient may become frankly demented or psychotic, sometimes with striking delusions. This also may occur shortly after starting T4 replacement.  Investigation of primary hypothyroidism Serum TSH is the investigation of choice; a high TSH level is found primary hypothyroidism. A low free T4 level confirms the hypothyroid state. In patients with autoimmune thyroiditis, titers of antibodies against thyroperoxidase and thyroglobulin are high , and other organ-specific antibodies may be present. Other abnormalities include the following: anaemia: which is usually normochromic and normocytic in type but may be macrocytic (sometimes this is due to associated pernicious anaemia) or microcytic (in women, due to menorrhagia or undiagnosed coeliac disease) hypercholesterolaemia and hypertriglyceridaemia  increased serum aspartate transferase( AST) levels, from muscle and/or liver increased serum creatine kinase(CK) levels, with associated myopathy hyponatraemia due to an increase in ADH and impaired free water clearance ( d.t. decrease in cardiac output ) *In severe, prolonged hypothyroidism, the electrocardiogram (ECG) classically demonstrates sinus bradycardia with low-voltage complexes and T- wave flattening or inversion. *Semen analysis shows an increase in abnormal sperm morphology.  Management Replacement therapy with levothyroxine (thyroxine, i.e. T4) is given for life. The starting dose will be 50-100 ug depending upon the severity of the deficiency and on the age and fitness of the patient, especially their cardiac performance. People with ischaemic heart disease require lower initial doses, especially if the hypothyroidism is severe and longstanding , so usually will then begin with 25 μg daily and perform serial electrocardiograms (ECGs), increasing the dose at about 4-week intervals if angina does not occur or worsen, and the ECG does not deteriorate. 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.  During pregnancy, an increase in T4 dosage of about 25–50 μg is often needed to maintain relatively stricter TSH range of 0.5–2.5 mU/L, and the necessity for optimal replacement during pregnancy is emphasized by the finding of reductions in cognitive function in children of mothers with elevated TSH during pregnancy. In cases where there is difficulty normalizing the TSH, compliance issues, concurrent medication that can interfere with thyroxine absorption (such as iron, calcium compounds and proton pump inhibitors) and undiagnosed coeliac disease should be considered. Complete suppression of TSH should be avoided because of the risk of atrial fibrillation and osteoporosis  Myxoedema coma Severe hypothyroidism, especially in the elderly, may present with this LIFE THREATENING EMERGENCY WITH HIGH MORTALITY RATE Clinical picture: Coma - Respiratory failure – Hypotension - Bradycardia – Hypothermia-Hypoglycemia – Pericardial effusion Precipitating factors: Infections - Trauma (including surgery) -Exposure to cold - Cardiovascular problems  Myxoedema coma is a medical emergency and treatment must begin before biochemical confirmation of the diagnosis. Suspected cases should be treated with an intravenous injection of triiodothyronine ( quicker onset of action) until there is sustained clinical improvement. In survivors, there is a rise in body temperature within 24 hours and, after 48–72 hours, it is usually possible to switch patients to oral levothyroxine. N.B. levothyroxine (T4) alone or combined with liothyronine (T3) can be used  Unless it is apparent that the patient has primary hypothyroidism, the thyroid failure should also be assumed to be secondary to hypothalamic or pituitary disease and treatment given with hydrocortisone should start, pending the results of T4, TSH and cortisol measurement. Other measures include slow rewarming , cautious use of intravenous fluids, broad-spectrum antibiotics and high-flow oxygen. Occasionally, assisted ventilation may be necessary  Subclinical hypothyroidism Serum TSH is raised, and serum T3 and T4 concentrations are at the lower end of the reference range. This may persist for many years, although there is a risk of progression to overt thyroid failure, particularly if antibodies to thyroid peroxidase are present or if the TSH rises above 10 mU/L. The term “subclinical” is somewhat misleading, since it does not refer to patients’ symptoms but rather refers only to serum hormone levels; in fact, such patients can have subtle manifestations of hypothyroidism (eg, fatigue, depression, hyperlipidemia) that may improve with a trial of levothyroxine replacement. Treatment with levothyroxine is normally recommended where the TSH is consistently above 10 mU/L, or when possible symptoms, high-titre thyroid antibodies, or lipid abnormalities are present. It is also considered best to normalize TSH during (and ideally before) pregnancy to avoid potential fetal adverse effects.  Non-thyroidal illness (‘sick euthyroidism’) It should be considered in patients without known thyroid disease who are found to have a low serum FT3, FT4 with a serum TSH that is not elevated and elevated serum reverse T3. Patients are clinically euthyroid. This syndrome can be seen in patients with severe illness, caloric deprivation, or major surgery. Pathogenesis is unknown but may include decreased peripheral conversion of T4 to T3, decreased clearance of rT3 generated from T4, and decreased binding of thyroid hormones to thyroxine-binding globulin (TBG). Treatment is of the underlying disorder and treatment with thyroid hormone replacement is not appropriate. When the underlying disorder is treated, results of thyroid tests normalize