LEARNING OBJECTIVES At the end of this chapter students should be able to: od by liver, kidney, 4 Explain the functions tests performe & Know about the list of biochemical tests performing 10 adrenal disorders @ Liver Function Tests Introduction + Liver plays a major role in storing blood {acts asa reservoir of blood). The parenchymal cells of the liver are related to the breakdown of hemo- globin to bilirubin and the removal of pigments. + Itplays a cenwal role in the metabo- lism: = Carbohydrates (glycogenesis, glycogenolysis, gluconeogenesis and alcohol metabolism). ® Proteins (transamination, oxidative deamination of amino acids, urea synthesis and protein synthesis). Lipids Hormones Vitamin: Bilirubin Bile acids ‘The hepatobiliary tee represents hepatic cells and biliary tract cells (Fig. 21.1). * Inflammation of the hepatic cells results in elevation of alanine aminotransferase or alanine transaminase (ALT), aspartate aminotransferase or aspartate transami- nase (AST) and possibly the bilirubin. * Inflammation of the biliary tract cells results predominantly in an elevation of the alkaline phosphatase (ALP) thyroid and adrenal gland diagnose liver, kidney, thyroid and Hepatic vein :— Hepatic artery Gallbladder Portal vein ‘Common bile duct lepatobiliary tree representing hepatic cells and biliary tract cells, * In liver disease there are crossover between purely biliary disease and hepatocellular disease. * To interpret these, the physician will look at the entire picture of the hepatocellular and biliary tract disease to determine which one is the primary abnormality. Indications of Liver Function Test Liver functions tests (LFTs) are useful in the differential diagnosis of jaundice. Detection of liver diseases Assessment of severity and progress of liver diseaseeeerrt oo sic processes in Liver Diseases jpecelt damage: This may vary from areas ‘cal damage t0 destruction of most of the “eels eading to liver failure, Syuses: Acute hepatitis may be viral ang snic Hepatitis is due to the continuing saan of infective oF toxic agents or that as, Sued with autoimmune response. } cirrhosis: Destruction of hepatic cells, » Biliary tract involvement: [tis associated with obstruction to bile flow (cholestasis) and may present as obstructive jaundice. ‘tee are two types of obstruction: Intrahepatic cholestasis: Mainly arises with iver cell destruction. Causes: Viral hepatitis, use of steroids (dur- ing pregnancy or in the case of woman tuking oral contraceptives). : Extrahepatic cholestasis, Causes: Gallstone in the common bile duct, carcinoma of the pancreas and cirrhosis of the bile duct. The LFTs are considered under the Mowing categories: ‘ Tests, which indicate the liver cell damage: © Aspartate transaminase * Alanine transaminase ‘Tess indicating biliary tract involvement: * Alkaline phosphatase * Gamma-glutamyl transferase (GGT) , | S'nucleotidase ‘s'sindicating impaired function: * Serum proteins * Bilirubin alProtein (Albumin and *butin) min ‘umn is the major protein present eltthe blood lngy Ct Synthesizes albumin. i 1s, fesents a major synthetic protein and | ater for the ability of the liver (0 | “size proteins. _ CHAPTER 21: Organ Function Tests * Itis one of the proteins synthesized by the liver. However, since it is easy {0 measure, it represents a reliable and inexpensive laboratory test for Physicians to assess the degree of liver damage presentin the particular Patient. Albumin level goes down when, liver gets severely damaged. Malnutrition can also cause low albumin with no associated liver disease. Serum Total Protein Estimation * Albumin estimation ® Globulins estimation. Methods: The serum proteins are estimated by differential precipitation of albumin and globulin fraction: * Biuret method + Albumin by dye-binding method Serum Protein Electrophoresis Thisisan evaluation ofthe types of proteins present in serum. % With an electrophoresis, major proteins can be separated and this results in four major types of proteins: 1. Albumin 2. a-globulins 3. Brglobulins 4. y-globulins Normal range: aw Total protein: 5.0-7.5 g/dL. 5-4.5 g/dL. g/dL y-globulin: 0.5-1.5 g/dL. Prothrombin Time Liver synthesizes clotting factors such as prothrombin, fibrinogen, factor V, VII the othrombl ntime(PT)is prolonged in the cases of hepatocellular damage. ‘The ability of the parenchymal cells ynthesize clotting factors is 2 to S| impaired.66 | Handbook of Applied Biochemistry, Nutrition and Dietetics Jaundice jaundice comes from French word jaune, which means yellow. Normal serum bilirubin is around 1.2 mg/100 mL. + Whenever the level exceeds more than the normal range it diffuses into the tissues and the skin and sclera of the eye turns yellow. This condition is called jaundice (icterus). * The yellowish coloration is caused by an excess amount of bilirubin in the skin. Bilirubin is a yellowish red pigment. Normally, small amounts of bilirubin are found in everyone's blood. + When too much bilirubin is made, the excess is dumped into the bloodstream and is deposited in tissues for temporary storage. 4 Jaundice in the infant appears first in the face and upper body and progresses downward towards the toes. Formation and Metabolism of Bilirubin (Fig. 21.2) Globin goes to globin pool RBC breakdown — Home + Giin—! NADPH Fe” enters iron poo! Le Home> Herne Biliverdin Bilirubin! Biliverdin reductase Fig. 21.2: Formation of bilirubin. Normal Values Total bilirubin = 0.2-1.0 mg% * Direct bilirubin = 0-0.2 mg% Indirect bilirubin = 0-0.8 mg% There are three different types of jaundice: 1. Hemolytic jaundice 2. Hepatic jaundice 3. Obstructive or posthepatic jaundice uses and biochemical findings of different types of jaundice are given in the Table 21.1. Van den Bergh’s Reaction Direct van den Bergh’s Test The conjugated water-soluble bilirubin when treated with diazo reagent [sodium nitrate (NaNO,) + sulfanilic acid] gives red color immediately. This is called direct van den Bergh’s test. The bilirubin react. ing directly is also called direct bilirubin. Indirect van den Bergh’s Test ‘The water-insoluble unconjugated bilirubin gives a positive van den Bergh's test only if methanol is added to the serum. This is in- direct van den Bergh’s test. This is also called indirect bilirubin. Urobilinogen in Urine and Feces * The presence of urobilinogen in a test sample can be shown by a test based on the production of red color when urobilinogen reacts with Ehrlich’s aldehyde reagent. + In hemolytic jaundice, there is increased formation of bilirubin, excretion into the intestine through the bile; therefore, there will be increased formation of urobilinogen in the intestine and increased level in the urine, and feces. Serum Enzymes in Liver Disease ‘The assay of serum enzymes is very useful in the differential diagnosis and monitoring of various hepatobiliary disorders. * Enzymes, which are normally present inside the hepatocytes, released into the blood when there is hepatocellular damage— markers for hepatocellular damage (viral hepatitis, cirrhosis of the liver). Enzymes, which are primarily membrane bound (plasma membrane or side of hepatocytes)—marker for cholestasis.f n n d 1 St he en tin g of side ood 3e— viral rane je of af Abnormal red cells, ¢ antibodies, abnormal hemoglobin slood conjugated bilirubin, Present (++) conjugated bilirubin, Normal vine ‘Unne bile salt (Hay’s test) Absent. Conjugated bilirubin Absent Fouchet's test) Uisbiinogen (Ehrlich’test) Present (+++) feces Urobitins Present (++) Serum enzymes Haine phosphatase (ALP) Normal Hance aminotransferase or Normal 2unne transaminase (ALT) ‘sparate aminotransferase or Normal 2anate transaminase (AST) Gnma-glutamyl Normal "rspeptidase (GGT) Scum Transaminases: AST and ALT "he ALT is specific for liver. 'slevel increases more than the normal ‘liver diseases (viral hepatitis, cirrhosis , “the liver). “CAST is not specific to liver, its level resin other forms of tissue damage such S:Mocardial infarction, muscle necrosis Tenal disorders. hi ‘line Phosphatase iggttM ALP estimation is the most sutly used biochemical test to put in i el apse e for cholestasis of intrahepatic or ‘ePatic origin. Organ Function Tests q Posthepatic/ Obstructive Vital hepatitis, toxic Extrahepatic hepatitis, intrahepatic cholestasis, gallstones, GRolestass of bile duct, tumor of le duct, gs and toxins carcinoma of pancreas Present (+4) Normal Increasesinearlyphase Present (++) and later decreases Absent Present Present Present Incteasesinearlyphase Absent 'n intrahepatic cholestasis Clay colored ecreases Moderatelyincreased Increased markedly Increased markedly Moderately increased Increased markedly Moderately increased Moderately increased increased markedly Normal level = 4-13 kA units or 40-140 U/L. Increase in serum level of alkaline phosphatase from liver is a very sensitive indicator of cholestasis. # Increased ALP level in cholestasis may be due to two features: 1. Regurgitation of ALP from bile to blood, 2. Increased synthesis from the cells lining the biliary canaliculi, Gamma-glutamyl Transferase Estimation + The GGT enzyme catalyzes the transfer of -glutamyl group from glutamyl peptides to another peptide or an amino acid,ndbook of Applied Biochemistry, Nutrition an © Itisa marker of cholestasis. The GGT level increases both in liver nid in cholestasis, but it is very dis high in cholestasis % itis also considered asa marker enzyme tn the patients of cirrhosis in chronic alcoholics. Normal value is 10-30 U/L. Different Types of Viral Hepatitis 1. Hepatitis A caused by hepatitis A virus (HAV). Markers: HAV antigen (Ag), HAV antibody (Ab) and HAV immunoglobulin M (IgM). Hepatitis B caused by hepatitis B virus (HBV). Markers: HBV deoxyribonucleic acid (DNA), hepatitis B surface antigen (HBsAg). hepatitis Be antigen (HBeAg), hepatitis B core antigen (HBcAg), antibody to HBsAg (anti-HBs), antibody to HBeAg (anti-HBe), HBc IgM and HBc immuno- globulin G (IgG). Hepatitis C caused by hepatitis C virus (HCV). Markers: HCV ribonucleic acid (RNA) qualitative, HCV RNA quantitative and anti-HCV. Hepatitis D caused by hepatitis delta virus (HDV). Markers: HDV Ag, HDV RNA [polymerase chain reaction (PCR)], HDV IgG, HDV IgM and HDV total (IgG + IgM). Hepatitis E caused by hepatitis E virus (HEV). Markers: HEV Ag, HEV IgG, HEV IgM and HEV Ab (total). § Renal Function Tests % Kidneys are the very important and vital organ. They perform many important functions toregulate the internal environment of the human body It is the main regulator of all the sub- stances of body fluids and responsible for maintaining homeostasis. © \d Dietetics Functions of Kidney The functional unit of a kid 21.3). Kidney has five importa 1. Urine formation Regulation of fluid and electrolyte balance Regulation of acid-base balance isnephron (Fy 1 functions, Hormonal function Excretion of non-protein nitrogen (Npx) substances. Kidney function tests are grouped under two headings: 1. The tests measuring glomerular filtration rate (GFR). 2. Creatinine clearance test It is the volume of plasma completely cleared off creatinine, which is excreted in the urine: UxV Ux Creatinine clearance = a or — 2. 3 4. 5. where, U-= Urine creatinine P = Plasma creatinine 1.73 = Generally accepted body surface area A= Body surface area of the patient under investigation Distal ‘Glomerulus convoluted tubule ‘Proximal ) convoluted P ‘Ascending. tubule limb \ \ Y Descending limb Collecting tubule g ‘Henle’s loop Structure of nephron.¢ The creatinine clearance is very eon. venient fo Measure GER, «Iris fulfilling all the requirement of the substance, which is ideal for me: GFR. s The amount of creatinine produced ig relatively constant and also itis not affected by the dietary intake. ‘asuring Normal Values Male: 105 +20 mL/min » Female: 95 + 20 mL/min Cinical Significance Abnormal results are lower than normal GER measurements and they indicate: « Acute tubular necrosis + Congestive heart failure + Dehydration Glomerulonephritis Shock + Acute nephrotic syndrome + Acute and chronic renal failure Study of Elimination of NPN Substances Study of Elimination of NPN Substances Tests measuring the retention of NPN substances in serum such as determination of urea, uric acid, creatinine, amino acids and ammonia. Urea * Urea constitutes about 45% of NPN substances. * Study oftheir elimination can be done with blood and urine. * One of the methods available for the determination of urea is diacetyl monoxime (DAM) method. Normal values Setum/Plasma urea: * 15-45 mg/dL CHAPTER 21: Organ Function Tests * 2.49-7.47 mmol/dl, * Blood urea nitrogen (BUN): 7-21 mg/ dt. Clinical significance Causes for urea increase are * Prerenal causes, = Cardiac decompensation = Water depletion due to decreased intake or excessive loss, & Increased protein breakdown * Renal causes are acute glomerulonephritis: = Chronic nephritis ® Polycystic kidney = Nephrosclerosis = Tubular necrosis Post-renal causes: © Any obstruction to urine flow (stone, tumor, enlarged prostate). Creatinine * Creatinine is a breakdown product of creatine, which is an important part of muscle, The most important source of energy inside cells is the adenosine triphosphate (ATP) molecule, with its high-energy phosphate bonds. * When one of these bonds is broken, energy is released and ATP becomes adenosine diphosphate (ADP). + Creatine phosphate represents a back-up energy source for ATP because it can quickly reconvert ADP back to ATP. % Overtime, the creatine molecule gradually degrades to creatinine. © Creatinine isa waste product, ie,, itcannot be used by cells for any constructive purpose. = The daily production of creatine and subsequently creatinine, depends on muscle mass, which fluctuates litte in most normal people over long periods of time. Creatinine is excreted from the body entirely by the kidneys.* With normal kidney function, the serum creatinine level should remain constant and normal Normal value * 0.8-1.4 mg/dL * Normal value ranges may vary slightly among different laboratories. Clinical significance Higher than normal levels may indicate: Nephrotic syndrome Chronic glomerulonephritis Acute tubular necrosis Dehydration Diabetic nephropathy Reduced renal blood flow Pyelonephritis Renal failure Urinary tract obstruction Lower than normal levels may indicate: = Muscular dystrophy (late stage) = Myasthenia gravis Uric Acid Normal value The normal value of uric acid is 2.5-7 mg%. Clinical significance Value increases in: + Renal failure Acute gout Pneumonia Sepsis Leukemia Polycythemia vera Anemia Value decreases in acromegaly eee Tests Measuring Tubular Function + Excretory function test + Tests to measure the concentrating and diluting ability: = Specific gravity determination = Osmolality determination Calcium and phosphorus In chronic renal failure, there is impaired Handbook of Applied Biochemistry, Nutrition a excretion of phosphate and progressive hy- perphosphatemia occurs. This result in the | nd Dietetics decreased plasma calcium concentratign giving rise to secondary hyperparathyroig ism. Determination of Amino Acids 4 Amino acids are a part of NPN Their determination is helpful only in some congenital renal disorders. If there is defect in reabsorption more amino acid will appear in the urine, this condition is called aminoaciduria, e.g cystinuria and homocystinuria. Aminoaciduria Aminoaciduria may be two types: 1. Primary aminoaciduria is due to an inherited enzyme deficiency, this is also called inborn error of me- tabolism. The defect is located in the pathway by which amino acid is metabolized or in the renal tubular system by which the amino acid is absorbed. Secondary aminoaciduria may be due to disease of the liver or renal tu- bular dysfunction, or protein energy malnutrition. In both the conditions metabolites of amino acids accumu- lated in the blood are excreted in the urine. There are several tests to detect these amino acids and their metabo- lites in the urine. Pathological Conditions of the Kidney Acute Glomerulonephritis Acute glomerulonephritis (AGN) is an acute inflammation of the glomeruli, which results in: = Oliguria Hematuria Proteinuria Anemia Increased blood urea and creatinine Decreased GFR * *fs. the presence of red blood cells (RBCs ine urine is an insufficient evidence tyecausse of the appearance of blood may be | from urinary tract. Nephrotic Syndrome 4 Itisaclinical entity characterized by massive proteinuria, edema, hypoalbuminemig hyperlipidemia and lipiduria, ; + Thesyndrome is having multiple causes, + Increased membrane permeability leads to massive proteinuria (mainly albumin loss). There will be reduction in plasma osmotic pressure and the fluid movement from vascular to interstitial space that leads toedema. Tubular Disease + Proximal renal tubular acidosis [reduced proximal tubular bicarbonate (HCO, ) reabsorption]. * Distal renal tubular acidosis (DRTA); there is an inability of tubular cells to create and maintain the usual pH difference between tubular, and blood. Urinary Tract Infection + Infection may occur in the bladder (cystitis) orit may involve the kidneys. * Diagnosis is made by the presence of bacterial concentration of more than 1 lakh colonies/mL of urine. Thyroid Function Tests The function of the thyroid gland is to take ‘odine found in many foods and convert it into thytoid hormones, i.e., thyroxine (T4), and | iiodothyronine (3). Thytoid cells are the only cells in the body, ‘hich can absorb iodine. These cells combine ‘odine and the amino acid tyrosine to make '3, and T4, Then the T3 and T4 are released 'nlo the bloodstream, and are transported in | thi for AGN. | m _CHAPTER 21: Organ Function Tests roughout the body where they control Ctabolism. Most of the cells in the body | depend upon thyroid hormones for regulation of their metabolism: * The hypothalamus, pituitary gland and the thyroid all play a part in the feedback and regulatory mechanisms involved in the Production of T4, and 73 from the thyroid gland. Thyroid-releasing hormone (TRH) i secreted by the hypothalamus and stimulates the production of the polypeptide thyroid-stimulating hormone (TSH) from the anterior pituitary, * The TSH then stimulates the production and release of T4, and T3 from the thyroid, * Once released, T4 and T3 then exert a negative feedback mechanism on TSH production. 74 is the main hormone produced by the thyroid. T3 is mainly produced by peripheral conversion of T4 * T3andT4 both act via nuclear receptors to increase cell metabolism. * The normal thyroid gland produces about 80% T4 and about 20% T3; however, T3 Possesses about four times the hormone ‘strength’ as T. * The 70-80% of T3 and T4 are transported in plasma by a thyroid-binding globulin (TBG), a plasma protein. The remaining 20-30% of T3 and T4 is transported by thyroxine-binding pre- albumin (TBPA) and albumin. + Only the unbound or ‘free’ portion (FT3, FTA) is active. Ivis the free portion of the thyroid hormones is the true determinant of the thyroid status of the patient. The evaluation of the thyroid status is not a simple procedure because it does not depend mainly on the measurement of circulating thyroid hormones. eft CSt TELL TLiLIaHandbook of Applied Biochemistry, Nutrition and Dietetics & The one or more factors may be abnormal and they are: ® The TRG concentration and tis degree of saturation with T3 and U4 @ Concentration of free 3 and TA = The state of the hypothalamus and anterior pituitary with their respect! outputs of TRH and TSH & The response of pituitary to TRH and response of the thyroid gland. ‘Thyroid disease is common, presents with many nonspecific symptoms so needs to be considered in many differentials and once diagnosed, needs to be regularly monitored for therapy. Asa consequence, TETs are the most commonly used endocrine test, Therefore, laboratory investigations of thyroid functions are useful in distinguishing patients with eu- thyroidism from those with hyperthyroidism and hypothyroidism, Common Thyroid Problems % Goiters: A thyroid goiter is a enlargement of the thyroid gland, Goiters are often removed because of cosmetic reasons or more commonly because they compress other vital structures of the neck include the trachea and the esophagus making breathing and swallowing difficult. Sometimes goiters will actually grow into the chest, where they can cause trouble is well, Thyroid cancer: It is malignancy; however, the vast majori have excellent long-term survival. * Solitary thyroid nodules: There re several characteristics of solitary nodules of the thyroid, which make them suspicious for malignancy. Although as many as 50% of the population will have @ nodule somewhere in their thyroid, the overwhelming majority of these are beni casionally, thyroid nodules can take on characteristics of malig Fequire either a necdle biopsy or s excision. fairly common es & Hyperthyrotdl Emeans too much thyroid hormone. Current methods used for treating @ hyperthyroid patient are radioactive iodine, anti-thyrold drugs or surgery. Each method has advantages and disadvantages and Is selected for individual patients. Hypothyroidism: It means too little thyroid hormone and is a common problem. In fact, hypothyroidism is often present for a number of years before it is recognized and treated. Hypothyroidism can even be associated with pregnancy. Thyroiditis: It is an inflammatory process ongoing within the thyroid gland. ‘Thyroiditis can present with a number of symptoms such as fever and pain, butitcan also present as subtle findings of hypo- or hyperthyroidis Tests for Thyroid Function ‘The thyroid function tests are grouped into two types: 1. The in vitro tests are: = Total serum T3 and T4 = Free serum T3 and T4 @ Blood TBG = Resin uptake test = Serum TSH = Thyroid autoantibodies 2. Invivo tests are: 3 Thyroid iodine uptake = TRH stimulation test = TSH stimulation test Total Serum T3 and T4 Determination by Immunoassay (RIA or ELISA) and Chemiluminescence Method Immunoassay and chemiluminescence method are direct measurements of the total T3 and T4 in the blood. The serum T4 ‘ays are more reliable than T3, because it is the major secretory product of thyroid gland. The majority of the T3 comes from Peripheral de-iodination of T4. This test—— aintyhelps to rule out hyperthyroidism and mnyroidism. Radioimmunoas tye ayme-linked immunosorb causes the choice say (RIA) ent assay clinical significance + Value increased in hyperthyroidism and decreased in hypothyroidism. + The values also decreased in when TBG concentration goes down due to loss in urine and liver disease. free T3 and T4 Determination this is a measure of circulatory T4 and T3 thatexists in the free form in the blood. The fee thyroid hormone concentration is in- dependent of changes in the concentration and affinity of thyroid-binding proteins and povides more reliable means of diagnosing thyroid dysfunction than measurement of total ‘Band T4 hormones. Normal values * Free T4 = 10-27 pmol/L. * Free T3 = 3-9 pmol/L Clinical significance Value increased in hyperthyroidism and ‘hytotoxicosis and decreased in hypothy- ‘dis, Hyperthyroidism ‘ipecthyroidism occurs as a consequence of “tessive thyroid hormone activity. Common ‘ies in include thyroiditis, Graves’ disease Toxic nodular goiter. agnosis * The initial laboratory investigation sth *Dossible diagnosis of hyperthyroid Should be a sensitive serum TSH assay, “hich will show reduced circulating levels TSH, * Low serum TSH is not specific for hy- Perthyroidism. It may also occur with non-thyroidal illness’ or with the use of some commonly prescribed drugs. Patients who have a low TSH may then go n to have further investigations such as (Table 21.2): | Free T4 and T3 assays: A subnormal TSH should trigger the measurement of FT4. If this is not elevated, FT3 should be measured to identify cases of T3-thyrotoxicosis. = Thyroid autoantibodies, e.g., thy- roid peroxidase antibodies (TPOAD), TSH receptor antibodies (TRAb). "= Radioactive iodine uptake: Thyroid scanning with either iodine-131 (most frequent) or "Tc helps to determine cause of hypothyroidism, e.g., diffuse pattern of uptake in Graves’ disease compared to one or more ‘hot’ nodules in toxic nodular hyperthyroidism. Hypothyroidism + Primary hypothyroidism occurs asa result of under secretion of thyroid hormone from the thyroid gland. 4 Causes include as Hashimoto's thyroiditis, irradiation and drugs such as lithium. Diagnosis 4 To diagnose primary hypothyroidism, needs to measure both TSH and FT4. Where TSH is more than 10 mU/L and FT4 below reference range, the diagnosis is overt primary hypothyroidism and the patient needs treatment with thyroid replacement therapy. 4 Secondary hypothyroidism is suggested by low within or mildly elevated TSH combined with a low FTA. Differentiating this from non-thyroidal illness can be difficult and clinical history, FT3 and sometimes anterior pituitary hormone tests are necessary."i Handbook of Applied Biochem sty Nutrition and Dietetics eT ee un Cua Rod se ST kava meet UU Ues Free 14 Usually raised Reduced ++ Graves disease Toxic multinodular, Reduced Raised of goiter normal Thyroiditis Reduced Increased increased Pregnanc! Normal Raised total T4 ee Normal FT4 Thyroxine Reduced Raised induced hyperthyroidism Secondary hypothyroi Additional diagnostic tests may include: 2 Thyroid autoantibodies—antithyroid peroxidase and antithyroglobulin antibodies. = Thyroid scan Subclinical Disease Subclinical thyroid disease is common in American population. Diagnosis is based solely on test results when to treat subclinical disease is contentious. Subclinical Hyperthyroidism % {tis diagnosed by low serum TSH, normal FT4 and FY3, in the absence of non- thyroidal illness or relevant drug therapy (Table 21.3) % May increases risk of developing atrial fibrillation (AF) and cardiovascular disease (ev) % The TFT» should be repeated at 3-6 shonths of earlier if elderly, or if patient | ha» pre-existing CVD, to d ermine idism may occur as a result of damage or disease of the pituitary or hy whether full blown hyperthyroidisin has | Free T3 Usually raised Other investigations Thyroid scan: Diffuse isotoy uptake is Thyroid peroxidase antibodies Raised or normal Thyroid scan: Functioning nodule with suppression of other tissue Thyroid scan: Low radioiodine uptake Thyroglobulin level, markedly raised erythrocyte sedimentation rate (ESR); often raised Increased Raised total T3 Positive pregnancy test Normal FT3 Thyroid scan: Low radioiodine uptake Thyroglobulin levels absent Raised or normal pothalamus. developed or if the subclinical picture has persisted. Subclinical Hypothyroidism Occurs where TSH is above reference range with a normal FT4 4 Diagnosis should be confirmed with repeat ‘TFTs after 3-6 months. “Where TSH is less than 10 mU/L, there is no consistent evidence of association with symptoms, hyperlipidemias or increased risk of CVD. Above this level, there is more evidence of progression to overt thyroid disease and worsening hyperlipidemia. “+ Thyroxin therapy is not recommended unless TSH more than 10 mU/L or, below this, if patients are pregnant, have a golter or are trying to conceive. Thyroid-binding Globulin Most of the thyroid hormones in the blood are attached to a protein called thyroid binding globulin. If there is an excess OF deficiency of this protein it alters the T oFwe ack oa) een CHAPTER 21: Organ Function Tests oe TSH Free Ta FreeT3, Other investigations . cnenctoans MOTaOr Nomalor Nomar Thyod node occu etel = fuced frequently with this condition and have a eee : Ae 596 risk of malignancy ode a faked oe yr Notmator High iters of autoantibodies in 95% tissue sskeuthyroid —Normalor Reduced Normalor Autoantibodies not present dine synarome reduced ly tation 3 measurement, but does not affect the indication of thyroid gland failure. Since action of the hormone. Ifapatientappears | __ TSH is normally low when the thyroid tohave normal thyroid function, but an | gland is functioning properly, the failure unexplained high or low T4, or T3, itmay | of TSH to rise when circulating thyroid be due to an increase or decrease of TBG. | __ hormones are low is an indication of Direct measurement of TBG can be done | _ impaired pituitary function. sent and will explain the abnormal value. Excess | * The new ‘sensitive’ TSH test will show TBG or low levels of TBG are found insome | _ very low levels of TSH when the thyroid families as a hereditary trait. These people | _is overactive (as a normal response of cture are frequently misdiagnosed as being | __ the pituitary to try to decrease thyroid hyperthyroid or hypothyroid, buttheyhave | stimulation). Interpretations of the nothyroid problem and need notreatment.| TSH level depend upon the level of + Normal value: 12-28 pg/mL. thyroid hormone; therefore, the TSH a + TBG value increased in hypothyroidism, | _ is usually used in combination with pregnancy and estrogen therapy. other thyroid tests such as the T4 RIA peat # TBG value decreased in hyperthyroid- || and T3 RIA. ism, nephrotic syndrome and liver : : oe disease, Thyroid-releasing Hormone Test vii + Innormal people, TSH secretion from the ad Measurement of Pituitary pituitary can be increased by giving a shot ae Prada containing TRH. oid luction of TSH ‘+ A baseline TSH of five or less usually goes ® Pituitary production of TSH is measured | upto 10-20aftergivingan injection of TRH, led byamethod referred to as RIA. Patients with too much thyroid hormone ow * Normally, low levels (<5 U) of TSH are | (thyroxine or triiodothyronine) will not ter sufficient to keep the normal thyroid gland | showa rise in TSH when given TRH. ., inctioning properly. + This ‘TRH test’ is presently the most “ When the thyroid gland becomes inefficient sensitive test in detecting early hy- Such as in early hypothyroidism, the TSH | perthyroidism. Patients who show od comes elevated even though the T4and | _—_ too much response to TRH (TSH d- may still be within the ‘normal’ range. rises greater than 40) may be hypo- or “ This tise in TSH represents the pituitary thyroid. ; ne ‘ands response to a drop in circulating | + This test is also used in cancer patients who are taking thyroid replacement to see ‘yroid hormone; it is usually the first ee thia $k of Applied Biochemistry, Nutriti re on sufficient medication. It is if they a ifthe pituitary sometimes used to measure gland is functioning The new ‘sensitive’ TSH test (above) has eliminated the necessity of performing a TRH test in most clinical situations. Thyroid lodine Uptake Scan A means of measuring thyroid function is to measure how much iodine is taken up by the thyroid gland. Remember, cells of the thyroid normally absorb iodine from our bloodstream (obtained from foods we eat) and use it to make thyroid hormone. Hypothyroid patients usually take up too little iodine and hyperthyroid patients take up too much iodine. The test is performed by giving a dose of radioactive iodine on an empty stomach. The iodine is concentrated in the thyroid gland or excreted in the urine over the next few hours. The amount of iodine that goes into the thyroid gland can be measured by a ‘thyroid uptake. At other times the gland will concentrate iodine normally, but will be unable to convert the iodine into thyroid hormone; therefore, interpretation of the iodine uptake is usually done in conjunction with blood tests. Reticularis Medulla ion and Dietetics Fasiculata Thyroid Scan ‘Taking a ‘picture’ of how well the thyroid gland is functioning requires giving radioisotope to the patient and letting the thyroid gland concentrate the isotope, Therefore, it is usually done at the same time that the iodine uptake test is performed. Although other isotopes such as technetium will be concentrated by the thyroid gland; these isotopes will not measure iodine uptake, which is what we really want to know because the production of thyroid hormone is dependent upon absorbing iodine. All scans are now done with radioactive iodine. Pregnant women should not have thyroid scans performed because the iodine can cause development troubles within the baby’s thyroid gland. Adrenal Gland ‘The adrenal gland comprises cortex and Medulla. Cortex has again three zones (Fig. 21.4): 1. Zona glomerulosa > produces mineralo- corticoids. 2, Zona fasciculata > produces glucocorti- coids. 3. Zona reticularis > secretes sex steroids like androgens and estrogens. ee) Glomerulosa Cortex Fig. 21.4; Histology of adrenal gland.K ssessment of Glucocorticoid Secretion plasma or serum cortisol level determina. is one of the methods for assessing the secretion of glucocorticoids. oral value 1} g-06 mg/dL at AM (250-850 nmol/L) ¢ 1emp/dL at PM (110-390 nmol/L) control of Cortisol Secretion cortisol and other glucocorticoids are gecreied in response to a single stimulator— | parenocorticotropic hormone (ACTH) | fom the anterior pituitary. ACTH is itself | secreted under control of the hypothalamic peptide corticotropin-releasing hormone 'CRH). The central nervous system is thus the commander and chief of glucocorticoid responses, providing an excellent example of dose integration between the nervous and | endocrine systems (Fig, 21.5). Pathophysiology: sadison's disease (Adrenal insufficiency): % Addison’s disease is a rare endocrine or hormonal disorder that occurs in all age goups certicotropin-releasing hormone; ACTH ‘““xonicotepic hormone) CHAPTER 21: Organ Function Tests + In this condition the adrenal gl: reduces insufficient amounts of steroit hormones (glucocorticoids and often mineralocorticoids % The disease is also called adrenal insufficiency, or hypocortisolism. Causes: * Failure to produce adequate levels of cortisol can occur for different reasons. The problem may be due to a disorder of the adrenal glands themselves (primary adrenal insufficiency) a Destruction of the adrenal glands by infection. a Their destruction by an autoimmune attack. % Inadequate secretion of ACTH by the pituitary gland (secondary adrenal insufficiency) Adrenocorticotropic Hormone Stimulation Test This is the most specific test for diagnosing | Addison's disease. In this test. blood cortisol, urine cortisol, or both are measured before and after a synthetic form of ACTH is given by injection. in the so-called short, or rapid, ACTH test, measurement of cortisol in blood is repeated 30-60 minutes after an intravenous | ACTH injection. The normal response after | an injection of ACTH is a rise in blood and urine cortisol levels. Patients with either form of adrenal insufficiency respond poorly or do not respond at all. Cushing's syndrome | = Cushing’ssyndrome isa hormonal disorder caused by prolonged exposure of the body’s tissues to high levels of the hormone cortisol. & In Cushing’s syndrome, the level of adrenal hormones, especially of the glucocorticoids (cortisol) is too high. Cause: | Excessive production of ACTH by the anterior lobe of the pituitary. Excessive production of adrenal hormones themselves (e.g.. because of a tumar).im Handbook of Applied Biochemistry, Nutrition and Dietetics * Ectopic ACTH syndrome: Some benign | other or malignant tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause over 50% of these cases. As a result of glucocorticoid therapy for some other disorder such as rheumatoid arthritis or Decreased glucocorticoid hormone synthesis. Symptoms * Hyperglycemia * High blood pressure * Severe protein catabolism results in thinning of skin, muscle wasting, Osteoporosis and negative nitrogen balance, There is a peculiar redistribution of fat in trunks, * Moon face * Central obesity and typical buffalo hump. * Resistant to infection and inflammatory response is impaired. * Facial hair growth + 24-hour Urinary Free Cortisol Level This is the most specific diagnostic test. The patient's urine is collected over a 24-hour period and tested for the amount of cortisol, the cortisol level is higher than 50-100 ug a day for an adult suggests Cushing's syndrome. The normal range may vary from laboratory to laboratory depending on the techniques they use. Dexamethasone Suppression Test This test is used to distinguish patients with excess production of ACTH due to Pituitary adenomas from those with ectopic ACTH-producing tumors, Patients are given dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 4 days. For the first 2 days, low doses of dexamethasone are Given. and for the last 2 days, higher doses are Biven. 24-hour urine sample collections are made before dexamethasone is administered and on each day of the test. Since cortisol and Blucocorticoids signal the pituitary 1g lower secretion of ACTH, the normal respons. after taking dexamethasone is a drop in bloog and urine cortisol levels. Different responses of cortisol to dexamethasone are obtained depending on whether the cause of Cushing's syndromeis a pituitary adenoma or an ectopic ACTH-producing tumor. The dexamethasone suppression test can Produce false-positive results in patients with depression, alcohol abuse, high estrogen levels, acute illness, and stress. Conversely, drugs such as phenytoin and phenobarbital may cause false-negative results in response to dexamethasone suppression. For this reason, Patients are usually advised by their physicians to stop taking these drugs at least one week before the test. CRH Stimulation Test This test helps to distinguish between patients with pituitary adenomas and those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors. Patients are given an injection of CRH, the corticotropin-releasing hormone which causes the pituitary to secrete ACTH. Patients with pituitary adenomas usually experience a rise in blood levels of ACTH and Cortisol. This response is rarely seen in patients with ectopic ACTH syndrome and practically never in patients with cortisol-secreting adrenal tumors. Mineralocorticoids + Itisa steroid hormone and mainly derived from the cholesterol. The mineralocorticoids get their name from their effect on mineral metabolism. The most important of them is the steroid aldosterone. Aldosterone acts on the kidney promoting the reabsorption of sodium ions (‘Na’) into the blood. * Water follows the salt and this helps maintain normal blood pressure. * Aldosterone also acts on sweat glands 10 Teduce the loss of sodium in perspiration. °CHAPTER 21: Organ Function T % Actvon taste sto Increase the sensitivity | Adrenal medulla: of the taste buds 10 nources of sodiurn, Seeretes % The secretion of aldosterone bs stimulated nine by: yaline (epinephrine) = A drop in the level of sodium fons In Noradrenaline (norepinephrine) the blood. & Arise in the level of potassium tons in | Functions the blood, 4% ‘The adre a consists of masses @ Angiotensin I of neurons that are part of the sympa ® Adrenocortocotropic hormone thetic branch of the autonomic nervous system i % Instead of releasing their neurotransmitters at a synapse, these neurons release them into the blood. ‘Thus, although part of the nervous system, the adrenal medulla functions as an endocrine gland, Primary aldosteronisin or Cohn’s syndrom @ Results from an aldosterone-secreting tumor which leads 10 elevated levels of plasma aldosterone, % The plastna pH in this condition increases because of hypokalemic alkalosis and the plasma osmolality also increases, deals with the liver function, renal function and thyroid function tests. Liver plays a major role in the metabolism. There is no single test to detect the abnormality of the liver because ofthe variety of the functions performed by the liver. Therefore, there are group of tests available to detect the abnormality of the liver. Detection of total protein, albumin, AST, ALI, bilirubin and GGT helps in the diagnosis of liver diseases and to diagnose the jaundice. Renal function tests performed to detect the diseases of the kidney, The kidneys perform many important functions to regulate the internal environmentof the human body. Its the main regulator of all the substances of body fluids and responsible for maintaining homeostasis, The major functions of the kidney are urine formation, regulation of fluid and electrolyte balance, regulation of acid-base balance, hormonal function and excretion of non-protein nitrogen (NPN) substances. The serum urea and creatinine determination helps to detect the abnormal function of the kidneys. Thyroid fonction tests help to diagnose the thyroid disorders, Thyroid gland secretes T3 and T4 upon stimulation by TSH. The reduced level of thyroid hormones is called hypothyroidism (goiter, Hashimoto's thyroiditis). The high level of thyroid hormones (hyperthyroidism) seen in Graves! disease, thyroiditis and toxic multinodular goiter. Thyroid iodine uptake scan will be done to measure how much iodine is taken up by the thyroid gland. Adrenal gland comprises medulla and cortex, The cortex has three regions such as zona glomerulosa which secretes mineralocorticoids (aldonerone), zona fasciculata secretes glucocorticoids and zona reticularis secretes sex steroids, Adrenal medulla secretes dopamine, epinephrine and norepinephrine. There are several tests done to detect the functions of adrenal gland for example ACTH stimulation and dexamethasone ‘uppression test, Elevated level glucocorticoids result in Cushing’s syndrome and reduced level leads wy Addison's disease. BYE