Clinical Biochemistry - Thyroid Disorders PDF

Lec.no. Clinical Biochemistry Dr.Feryal Hashim Hyperthyroidism (Thyrotoxicosis): is the consequence of findings that result when peripheral tissues are presented with, and respond to, an excess of thyroid hormone. It can be the result of excessive thyroid hormone ingestion,...

Lec.no. Clinical Biochemistry Dr.Feryal Hashim Hyperthyroidism (Thyrotoxicosis): is the consequence of findings that result when peripheral tissues are presented with, and respond to, an excess of thyroid hormone. It can be the result of excessive thyroid hormone ingestion, leakage of stored thyroid hormone from storage in the thyroid follicles, or excessive thyroid gland production of thyroid hormone. The causes of hyperthyroidism can be divided into two subcategories based on the results of the Radioactive Iodine Uptake (RAIU): I- Uptake is increased (or normal) in: Graves' disease, toxic multinodular goiter, TSH-secreting tumors, trophoblastic tumors, and toxic adenoma. II- Uptake is suppressed in subacute thyroiditis (SAT), silent thyroiditis, chronic thyroiditis, thyroid carcinoma. The signs and symptoms of hyperthyroidism are attributable to the effects of excess thyroid hormone in the circulation, catabolic-hypermetabolic effect in various tissues and increased sensitivity to the catecholammes. -Symptoms of hyperthyroidism include: 1)-Nervousness and irritability, tremor, sudden paralysis,mental disturbances, sleep disturbances (including insomnia), 2)-Changes in vision, photophobia, diplopia, or exophthalmos, 3)-Palpitations and tachycardia, 4)-Heat intolerance or increased sweating (perspiration), dependent lower- extremity edema, fatigue and muscle weakness, 5)-Weight loss, alterations in appetite, frequent bowel movements, 6)-Menstrual disturbance, impaired fertility, gynecomastia, amenorrhea. 1 -Hyperthyroidism may associate with the following clinical abnormalities features: 1- Hypercalcaemia occasionally found in patients with severe thyrotoxicosis because of increase bone cells turnover due to direct action of thyroid hormone. 2- Hypocholesterolaemia can occur, due to increased LDL clearance. 3-Hypokalaemia may occur, because of thyrotoxic periodic paralysis 4- Plasma SHBG is increased 5- Plasma Creatine kinase , alkaline phosphatase (ALP) may be increased due to thyrotoxic myopathy. 6- Ketosis and negative nitrogen balance. Types of Hyperthyroidism: 1 – Graves ' disease : is a consequence of autoantibodies called thyroid- stimulating immunoglobulins (TSIs) , because TSIs are not regulated by normal feedback mechanisms , and interacts with the TSH receptor of the thyroid follicular cell membrane therefore there is a gradually increase in thyroid hormone levels. It occurs six times more commonly in women than in men. The classic clinical features in Graves' disease include: diffuse thyrotoxic goiter, exophthalmos (bulging eyes), pretibial myxedema and dermopathy (skin changes in the lower extremities that have an orange peel texture). Exophthalmos is due to infiltration of the retro-orbital space with lymphocytes, mast cells, and mucopolysaccharides. 2 – Thyroiditis : is an inflammation of the thyroid gland. The disorder has been classified as acute (suppurative), subacute (SAT) or (nonsuppurative). 2 I- Acute thyroiditis : is caused by a bacteria, mycobacteria, fungi, or parasites, and is characterized by abscess and suppuration. Symptoms include tenderness and swelling of thyroid gland, fever, and malaise. This form of thyroiditis is rare, because of the gland's inherent resistance to infection manifested by its complete encapsulation, rich blood supply, lymphatic drainage, and high iodide content. TT4 and T3 levels are normal. II- Subacute thyroiditis (SAT): The simplest classification of forms of subacute thyroiditis involved postpartum thyroiditis, painless thyroiditis, and painful thyroiditis. These conditions are associated with inflammation of the thyroid gland, leakage of stored thyroid hormone, and then repair of the gland. SAT presents in three phases.These conditions are often associated with a thyrotoxic phase when thyroid hormone is leaking into the circulation, a hypothyroid phase when the thyroid gland is repairing itself, and a euthyroid phase when the gland is repaired. These phases can last from weeks to months. -Postpartum thyroiditis : is the most common form of subacute thyroiditis. It occurs in 3–16 % of women in the postpartum period. It is strongly associated with the presence of TPO antibodies and chronic lymphocytic thyroiditis. Thyroid hormone levels usually return to normal after several months to 4 years’ postpartum, 25%–50% of patients have persistent hypothyroidism, goiter, or both. -Silent or painless thyroiditis : the ESR is normal. The etiology of painless thyroiditis is unclear but is believed to be autoimmune, the clinical course runs through three phases, similar to SAT. Recovery is the rule, but some patients may have persistent goiter, antithyroid antibodies, or chronic thyroiditis. -Painful thyroiditis: also called subacute granulomatous, subacute nonsuppurative thyroiditis, is characterized by neck pain, low-grade fever, myalgia, a tender diffuse goiter.Viral infections may trigger this condition. TPO antibodies are usually absent; erythrocyte sedimentation rate (ESR) and thyroglobulin levels are often elevated. Thyroid hormones are usually mild to moderately increase. 3 3 – Miscellaneous causes of hyperthyroidism : rare forms, exist in secondary hyperthyroidism (pituitary), the TSH will be elevated despite a high level of fT4, due to the presence of a TSH-secreting pituitary adenoma. Excessive TSH secretion also found without evidence of a pituitary tumor may be due to the hypersecretion of TRH tertiary hyperthyroidism, loss of the inhibition of TSH secretion that normally produced by excessive levels of thyroid hormones, or the presence of thyroid hormone resistance syndrome in the pituitary gland. 4 –Sub clinical Hyperthyroidism : occurs in patients showing no clinical symptoms of hyperthyroidism, but whose TSH levels are less than 0.1µU/mL to the lower limits of the normal range and normal free T4 and T3 estimates. -Laboratory Evaluation: Hyperthyroidism of any cause (except excess TSH production) results in a lower-than normal TSH level, almost all overt hyperthyroid patients have undetectable rather than mildly decreased TSH. TSH levels may be slightly depressed during pregnancy, in these cases; the fT4 test would be useful. The diagnosis of hyperthyroidism becomes more complex with sick patients due to changes in thyroid-binding proteins and the presence of circulating inhibitors. The key result in such cases is whether the TSH is below 0.1 µU/mL. Large doses of dopamine or corticosteroids may also result in decreased TSH levels, but rarely below 0.1 µU/mL. It is important to screen for antithyroglobulin autoantibodies whenever thyroglobulin is being measured. Approximately 25% of patients with well- differentiated thyroid cancer will have antithyroglobulin autoantibodies. –Treatment of Hyperthyroidism : The objective of treatment is to lower the thyroid hormones to normal and to minimize the symptoms; treatment can be achieved by antithyroid medication, radioactive iodine therapy ,or thyroidectomy.The treatment with radioactive iodine (131I) is currently the most popular technique. However, it is contraindicated during pregnancy. 4 Antithyroid drugs, such as propylthiouracil, methimazole, and carbimazole, have been used to inhibit the synthesis, release, or peripheral activation of thyroid hormones. Beta-blockers, such as propranolol, may be useful as an adjunct therapy. The antithyroidal medications carry a significant risk profile that includes rash,hepatoxicity, agranulocytosis and aplastic anemia. the TSH levels tend to stay undetectable for extended periods. Laboratory findings in hyperthyroidism TT4, TT3, TSH TRH- TSI/ RAIU Likely Diagnosis fT4 fT3 stimulation TSHR- test Ab ↑ ↑ ↓,U Blunted +ve ↑ -diffuse Autoimmune: -Graves disease. ↑ ↑ ↓,U Blunted +ve ↓- poor -Silent thyroiditis, uptake -Postpartum thyroiditis ↑ ↑ ↓,U Blunted -ve ↑-Nodular -Toxic adenoma, hot -Multinodular goiter ↑ ↑ ↓,U Blunted -ve ↓-poor -Painful thyroiditis uptake ↑ ↑ ↑ Response ----- ----- -Pituitary resistance to on TSH thyroid hormone ↑ ↑ ↑ No response ----- ----- - Secondary hyperthyroidism on TSH (Pituitary tumor). N N ↓-mild --------- ----- --------- -Subclinical Hyperthyroidism N ↑ ↓ ----------- ----- --------- -T3 Toxicosis. (Blunted): lower than normal, (N): Normal, (U): undetectable,(TSHR- Ab):TSH receptor antibody. 5 Lithium may inhibit iodination by interfering with thyroglobuline and change its structure then inhibit iodination. Lithium concentrate in thyroid gland 3-4 time more than plasma. Thus in lithium therapy iodine was concentrated in thyroid gland but not form T4 or T3. 6