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hyperthyroidism (Table 26 5) in patients who are clinically euthyroid Serum T4 is frequently low in patients with severe illness, caloric deprivation, or major surgery who have accelerated peripheral metabolism of serum T4 to reverse T3 (rT3) Furthermore, in most patients who are critically ill, there is a circulating inhibitor of thyroid hormone binding to serum thyroid-binding proteins (TBPs) This causes the RT3U to be misleadingly low, causing the computed FT4I to be very low The presence of a very low serum T4 in severe nonthyroidal illness indicates a poor prognosis Direct assays of FT4 often show low levels of FT4 in severe illness Because studies of giving replacement T4 to such patients have shown no improvement in survival, they are considered euthyroid Serum TSH tends to be suppressed in severe nonthyroidal illness, making the diagnosis of concurrent primary hypothyroidism quite difficult, although the presence of a goiter suggests the diagnosis The clinician must decide whether such severely ill patients (with a low serum T4 but nonelevated TSH) might have hypothyroidism due to pituitary insufficiency Patients without symptoms of prior brain lesion or hypopituitarism are very unlikely to suddenly develop hypopituitarism during an unrelated illness Patients with diabetes insipidus, hypopituitarism, or other signs of a central nervous system lesion may have T4 given empirically True secondary hypothyroidism due to direct dopamine suppression of TSH-secreting cells may develop in patients receiving prolonged dopamine infusions Certain antiseizure medications cause low serum FT4 levels by accelerating hepatic conversion of T4 to T3; serum TSH levels are normal
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Ando T et al Thyrotropin receptor antibodies: new insights into their actions and clinical relevance Best Pract Res Clin Endocrinol Metab 2005 Mar;19(1):33 52 [PMID: 15826921] Bowen RA et al Effect of blood collection tubes on total triiodothyronine and other laboratory assays Clin Chem 2005 Feb;51(2): 424 33 [PMID: 15576427] Helfand M; US Preventive Services Task Force Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the US Preventive Services Task Force Ann Intern Med 2004 Jan 20;140(2):128 41 [PMID: 14734337]
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Weakness, fatigue, cold intolerance, constipation, weight change, depression, menorrhagia, hoarseness Dry skin, bradycardia, delayed return of deep tendon reflexes Anemia, hyponatremia T4 and radioactive iodine uptake usually low TSH elevated in primary hypothyroidism
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Hypothyroidism is common, affecting over 1% of the general population and about 5% of individuals over age 60 years Thyroid hormone deficiency affects almost all body functions The degree of severity ranges from mild and unrecognized hypothyroid states to striking myxedema The fluid retention seen in myxedema is caused by the interstitial accumulation of hydrophilic mucopolysaccharides, which leads to lymphe-
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Table 26 4 Factors that may cause aberrations in laboratory tests that may be mistaken for primary hypothyroidism1
Low Serum T4 or T3 Laboratory error Acute psychiatric problems Cirrhosis Nephrotic syndrome Familial thyroid-binding globulin deficiency Severe illness Drugs Androgens Asparaginase Carbamazepine Chloral hydrate Corticosteroids Diclofenac (T3) Fenclofenac Flouracil Halofenate Mitotane Naproxen (T3) Nicotinic acid Oxcarbazepine Phenobarbital Penytoion (total T4 may be as low as 2 mcg/dL) Salicylates (large doses T3 and T4) Sertraline T3 therapy True primary hypothyroidism may coexist T4, levothyroxine; T3, triiodothyronine; TSH, thyroid-stimulating hormone
Table 26 5 Factors that can cause aberrations in laboratory tests that may be mistaken for spontaneous clinical primary hyperthyroidism1
High Serum T4 or T3 Laboratory error Collecting serum in vial with gel barrier T3 Acute psychiatric problems (30%) Acute medical illness (eg, acute intermittent porphyria AIDS (increased thyroidbinding globulin) Autoimmunity Hepatitis: acute or chronic active Primary biliary cirrhosis Pregnancy (especially with morning sickness) Hypermesis gravidarum Familial thyroid-binding abnormalties Famial generalized resistance to thyroid (Refetoff syndrome) Drugs Amiodarone Amphetamines Clofibrate Estrogens (oral) Heparin (dialysis method) Heroin Thyroid hormone therapy Methadone Perphenazine Tamoxifen True clinical hyperthyroidism may coexist T4, levothyroxine; T3, triiodothyronine; TSH, thyroid-stimulating hormone; hCG, human chorionic gonadotropin; NSAIDs, nonsteroidal anti-inflammatory drugs
High Serum TSH Laboratory error Autoimmune disease (assay interference) Heterophile antibodies Anti-mouse antibodies Strenuous exercise (acute) Sleep deprivation (acute) Recovery from nonthyroidal illness (transient) Acute psychiatric admissions (14% transient) Elderly especially women (10%, mild elevations) Low Serum TSH Laboratory error Autonomous thyroid or thyroid nodule Acute corticosteroid administration Elderly euthyroid Nonthyroidal illness (severe) Pregnancy (especially with morning sickness) hCG-secreting trophoblastic tumors Drugs Thyroid hormone Amphetamines Dopamine Dopamine agonists
Calcium channel blockers (nifedipine, verapamil)
dema Hyponatremia is the result of impaired renal tubular sodium reabsorption due to reductions in Na+ K+-ATPase Hypothyroidism may be due to primary disease of the thyroid gland itself or lack of pituitary TSH Florid hypothyroidism, ie, myxedema and cretinism, is readily recognized on clinical grounds alone, but mild hypothyroidism often escapes detection without screening (ie, serum TSH) Maternal hypothyroidism during pregnancy results in offspring with IQ scores that are an average 7 points lower than those of euthyroid mothers Goiter may be noted when hypothyroidism is due to Hashimoto s thyroiditis, iodide deficiency, genetic thyroid enzyme
defects, drug goitrogens (lithium, iodide, propylthiouracil or methimazole, phenylbutazone, sulfonamides, amiodarone, interferon- , interferon- , interleukin-2), food goitrogens in iodide-deficient areas (eg, turnips, cassavas) or, rarely, peripheral resistance to thyroid hormone or infiltrating diseases (eg, cancer, sarcoidosis) A hypothyroid phase occurs in subacute (de Quervain s) viral thyroiditis following initial hyperthyroidism Goiter is usually absent when hypothyroidism is due to deficient pituitary TSH secretion, or destruction of the gland by surgery, external radiation, or 131I Patients who have
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