EN1 and 2

Download as pdf or txt
Download as pdf or txt
You are on page 1of 11

‭MID-LECT4-ENDOCRINOLOGY 2‬ ‭●‬ T ‭ he more protein is present the more thyroxine binding protein is present‬

‭Thyroid Gland‬ ‭and the more T3 and T4 is increase‬


‭●‬ ‭located in‬‭front of the lower neck‬ ‭Biosynthesis of Thyroid Hormones‬
‭○‬ ‭Below the voice box or larynx‬ ‭●‬ ‭Conversion of T4 to T3 takes place in many tissues, particularly‬‭the liver and‬
‭■‬ ‭Two lobes:‬ ‭the kidney‬
‭❖‬ ‭Connected by a narrow band called “isthmus”‬ ‭●‬ ‭Free Hormones‬‭(FT3 and FT4)‬
‭■‬ ‭By 11 weeks gestation the gland begins to produce measurable‬ ‭○‬ ‭physiologically‬‭active‬‭portions of the thyroid hormones‬
‭amount of hormone‬ ‭●‬ ‭Protein bound hormones‬
‭●‬ ‭bow tie or butterfly like‬ ‭○‬ ‭metabolically‬‭inactive‬
‭●‬ ‭The gland here divided into lobules and each of the lobules is composed of‬ ‭○‬ ‭do not enter‬‭cells‬
‭20-40 follicles‬ ‭○‬ ‭biologically inert‬
‭●‬ ‭Follicles:‬‭structural units of thyroid cells‬ ‭○‬ ‭function as‬‭storage site‬‭for circulating thyroid hormones‬
‭○‬ ‭Follicles are separated by highly vascular connective tissue‬ ‭●‬ ‭Hypothalamic-pituitary-thyroid axis‬
‭○‬ ‭Ring shaped structures‬ ‭○‬ ‭Its a neuroendocrine system that regulates the production and secretion‬
‭○‬ ‭Considered as fundamental structural unit of thyroid gland‬ ‭of the thyroid hormone‬
‭○‬ ‭Considered as site of thyroid hormone synthesis and storage‬ ‭●‬ ‭Iodine intake below‬‭50 ug/day = deficiency of hormone‬‭secretion‬
‭●‬ ‭Thyroid gland is also contains of parafollicular cells (C cells)‬ ‭●‬ ‭Thyroid hormones affect‬‭synthesis, degradation, intermediate‬‭metabolism of‬
‭○‬ ‭Responsible for the synthesis and secretion of‬‭calcitonin‬ ‭adipose tissue and circulating lipids‬
‭■‬ ‭Hormone important for the calcium metabolism‬ ‭Functions of Thyroid Hormones‬
‭●‬ ‭Colloid: homogeneous viscous fluid‬‭consisting mainly‬‭of a‬‭glycoprotein‬ ‭●‬ ‭For tissue growth‬
‭iodine complex‬‭called t‬‭hyroglobin‬ ‭●‬ ‭For development of the CNS‬
‭○‬ ‭T‭h ‬ yroglobin - rich in amino acid tyrosine‬ ‭●‬ ‭Elevated heat production‬
‭■‬ ‭Act as preformed matrix that consist the tyrosine groups‬ ‭●‬ ‭Control of oxygen consumption‬
‭■‬ ‭Glycoprotein that are stored in the follicular colloid of thyroid‬ ‭●‬ ‭It influences carbohydrate and protein metabolism‬
‭gland‬ ‭●‬ ‭For energy conservation‬
‭●‬ ‭secretes T3 and T4 and calcitonin‬ ‭Major Thyroid Hormones‬
‭Types of cells:‬ ‭Triidothyronine (T3)‬
‭●‬ ‭Follicular cells: secrete T3 and T4‬ ‭●‬ ‭Has the most active thyroid hormonal activity‬
‭○‬ ‭control the rate at which cells burn fuels from food for energy‬ ‭○‬ ‭Almost 75-80% is produced from the tissue deiodination of the T4‬
‭○‬ ‭CNS activity and brain development‬ ‭●‬ ‭An‬‭increased in the plasma level of the T3‬‭(fist abnormalities‬‭seen) can‬
‭○‬ ‭cardiovascular stimulation, bone and tissue growth and development‬ ‭correlate to‬‭hyperthyroidism‬
‭○‬ ‭GI regulation and sexual maturation‬ ‭●‬ ‭Principal application of this hormone is for diagnosing‬‭T3 thyrotoxicosis‬
‭●‬ ‭Parafollicular cells (C-cells):‬ ‭○‬ ‭T3 thyrotoxicosis -‬‭It is a hyperthyroidism with elevated‬‭serum T3 but T4‬
‭○‬ ‭Secrete:‬ ‭and FT4 is normal‬
‭■‬ ‭calcitonin‬ ‭●‬ ‭Better indicator of‬‭recovery from hyperthyroidism‬‭as well as the recurrence‬
‭■‬ ‭regulation of calcium‬ ‭of hyperthyroidism‬
‭T3 and T4‬ ‭●‬ ‭Reference values:**‬
‭○‬ ‭80 to 200 ng/dL or 1.2 to 3.1 nmol/L (Adults)‬
‭Hormone‬ ‭Bound (Albumin,‬ ‭Free‬ ‭○‬ ‭105 to 245 ng/dL or 1.8 to 3.8 nmol/L (Children)‬
‭Prealbumin, Globulin)‬ ‭Tetraiodothyronine (T4)‬
‭T3‬ ‭99.8%‬ ‭0.2%‬ ‭●‬ ‭Principal secretory product‬
‭T4‬ ‭99.98%‬ ‭0.02%‬
‭●‬ ‭Major fraction of organic iodine in the circulation‬
‭●‬ ‭T3: globulin and albumin only‬
‭●‬ ‭A‬‭prehormone‬‭for T3 production‬
‭●‬ ‭T4: albumin (10%), pre-albumin (30%:TBPA), globulin (60%:TBG)‬
‭○‬ ‭All circulation T4 here is originates from the thyroid gland‬
‭Biosynthesis of Thyroid Hormones‬ ‭●‬ ‭The amount of serum T4 is a good indicator of‬‭thyroid‬‭secretory rate‬
‭●‬ ‭Iodine‬‭is the‬‭most important element in the biosynthesis‬‭of thyroid hormones‬ ‭●‬ ‭Reference values**‬
‭●‬ ‭Recommended Daily Intake of Iodine-‬‭150 ug‬ ‭○‬ ‭5.5 to 12.5 ug/dL or 71 to 161 nmol/L (adults)‬
‭●‬ ‭Found in seafood, dairy products, iodine-enriched breads, and vitamins‬ ‭○‬ ‭11.8 to 22.6 ug/dL or 152 to 292 nmol/L (neonates)‬
‭●‬ ‭The activity of thyroid hormone is dependent on the‬‭location and number of‬ ‭DISEASES ASSOCIATED WITH HORMONES OF THE THYROID GLAND‬
‭iodine atoms‬
‭●‬ ‭Screening have been done here for thyroid disorder‬
‭●‬ ‭Important because:‬‭Iodination of tyrosine residues‬‭in thyroglobulin results in‬
‭○‬ ‭Which is usually recommended when the person reaches 35 years old‬
‭formation of‬‭monoiodothyronine (MIT)‬‭and‬‭diiodothyronine‬‭(DIT)‬
‭every 5 years‬
‭○‬ ‭Monoiodothyronine (MIT)‬‭and‬‭Diiodothyronine (DIT)‬‭can result to the‬
‭CLINICAL DISORDERS‬
‭formation of the active forms of thyroid hormone like T3 and T4‬
‭Two major disorder‬
‭○‬ ‭Two active form of thyroid hormones‬
‭HYPERTHYROIDISM‬ ‭HYPOTHYROIDISM‬
‭■‬ ‭T3 consist of one‬‭monoiodothyronine and one diiodothyronine‬ ‭Thyrotoxicosis‬ ‭Primary Hypothyroidism‬
‭residues‬ ‭• Hashimoto’s disease‬
‭■‬ ‭T4 consist of two diiodothyronine residues‬ ‭• Myxedema‬
‭Iodothyronine 5-deiodinase‬ ‭Grave’s Disease (Diffuse Toxic Goiter)‬ ‭Secondary Hypothyroidism‬
‭A.‬‭Type 1 Iodothyronine 5-deiodinase‬ ‭Riedel’s Thyroiditis‬ ‭Tertiary Hypothyroidism‬
‭●‬ ‭the most abundant form,‬ ‭Subclinical Hyperthyroidism‬ ‭Congenital Hypothyroidism/Cretinism‬
‭●‬ ‭found mostly in the‬‭liver and kidney‬ ‭Subacute granulomatous/ Subacute‬ ‭Subclinical Hypothyroidism‬
‭Nonsuppurative Thyroiditis/ De Quervain’s‬
‭●‬ ‭responsible for the‬‭largest contribution‬‭to the circulating‬‭T3 pool.‬
‭Thyroiditis (painful thyroiditis)‬
‭B.‬‭Type 2 Iodothyronine 5-deiodinase‬
‭●‬ ‭found in the‬‭brain and pituitary gland‬ ‭Hyperthyroidism‬
‭●‬ ‭maintain constant levels of T3 in the‬‭central nervous‬‭system.‬ ‭Primary Hyperthyroidism‬
‭●‬ ‭Its activity is decreased when levels of circulating T4 are high and increased‬
‭●‬ ‭Elevated‬‭T3 and T4‬
‭when levels are low.‬
‭●‬ ‭Decreased‬‭TSH‬
‭Three Thyroid Hormones Major Binding Proteins‬ ‭●‬ ‭Decreased‬‭TRH‬
‭in order of significance‬
‭Secondary Hyperthyroidism‬
‭A.‬‭Thyroxine-Binding Globulin (TBG)‬
‭●‬ ‭Increased‬‭TSH and FT4‬
‭●‬ ‭Transports‬‭70-75%‬‭of total T4‬ ‭○‬ ‭(due to the primary lesion in the‬‭pituitary gland‬‭)‬
‭●‬ ‭Transports majority of T3 → affinity for T3 is weaker than T4‬ ‭○‬ ‭Usual signs and symptoms are tachycardia, tremors, weight loss, heat‬
‭B.‬‭Thyroxine-Binding Prealbumin‬ ‭intolerance, emotional lability and menstrual changes‬
‭●‬ ‭also known as‬‭Transthyretin‬
‭●‬ ‭Transports 15 to 20% of total T4‬
‭●‬ ‭T3‬‭has a very weak or sometimes has‬‭no affinity for‬‭prealbumin‬
‭C.‬‭Thyroxine-Binding Albumin‬
‭●‬ ‭Transports the‬‭remaining T3‬
‭●‬ ‭Transports‬‭10% of T4‬
‭Thyrotoxicosis‬ ‭Hashimoto’s disease (Chronic Autoimmune Thyroiditis)‬
‭●‬ I‭s applied to a group of syndromes caused by high levels of‬‭free thyroid‬ ‭●‬ ‭The thyroid is replaced by a nest of lymphoid tissue‬
‭hormones‬‭in the circulation‬ ‭○‬ ‭They synthesized T-lymphocyte or autoantibodies that bind to the cell‬
‭●‬ ‭TSH is‬‭low‬ ‭membrane and it causes the lysis and inflammatory reaction‬
‭●‬ ‭FT4 is‬‭normal‬ ‭●‬ ‭There is an associated with the enlargement of the thyroid gland and goiter is‬
‭●‬ ‭Increased‬‭FT3‬ ‭present‬
‭●‬ ‭Also called: T3 Thyrotoxicosis/‬‭Plummer’s Disease‬ ‭●‬ ‭acquired hypothyroidism in later childhood due to development of autoantibodies‬
‭Signs and Symptoms‬ ‭to thyroid tissue components‬
‭●‬ ‭Method for testing:‬
‭SIGNS‬ ‭SYMPTOMS‬ ‭○‬ ‭TPO antibody (+)‬
‭‬
● ‭ achycardia‬
T ‭‬
● ‭ ervousness, irritability, anxiety‬
N ‭○‬ ‭Increased TSH‬
‭●‬ ‭Tremor‬ ‭●‬ ‭Tremor‬ ‭Myxedema‬
‭●‬ ‭Warm, moist, flushed, smooth skin‬ ‭●‬ ‭Palpitations‬ ‭●‬ ‭Describe as peculiar non-pitting‬‭swelling‬‭of the skin‬
‭●‬ ‭Lid lag, widened palpebral fissures‬ ‭●‬ ‭Fatigue, weakness, decreased‬ ‭○‬ ‭The skin becomes infiltrated by mucopolysaccharides‬
‭●‬ ‭Ophthalmopathy (Grave’s disease)‬ ‭exercise tolerance‬
‭●‬ ‭hypothyroidism during the adult years‬
‭●‬ ‭Goiter‬ ‭‬
● ‭Weight loss‬
‭●‬ ‭Brisk deep tendon reflexes‬ ‭●‬ ‭Heat intolerance‬ ‭●‬ ‭Severe form of primary hypothyroidism‬
‭●‬ ‭Muscle wasting and weakness‬ ‭●‬ ‭Hyperdefecation‬ ‭●‬ ‭Clinical Features: puffy face, weight gain, slow speech, thin eyebrows, dry skin,‬
‭●‬ ‭Dermopathy/pretibial myxedema‬ ‭●‬ ‭Menstrual changes (oligomenorrhea)‬ ‭yellow skin and anemia‬
‭(Grave’s disease)‬ ‭●‬ ‭Prominence of eyes‬ ‭Secondary Hypothyroidism‬
‭ ‬ ‭Osteopenia, osteoporosis‬

‭‬ D
● ‭ ue to pituitary‬‭destruction‬‭or pituitary‬‭adenoma‬
‭●‬ ‭T3 and T4 are‬‭low‬
‭ rave’s Disease (Diffuse Toxic Goiter)‬
G
‭●‬ ‭TSH is‬‭low‬
‭●‬ ‭The common cause of‬‭Thyrotoxicosis‬
‭Tertiary Hypothyroidism‬
‭●‬ ‭Autoimmune disease in which the antibodies are produced which activate‬
‭‬ D
● ‭ ue to‬‭hypothalamic disease‬
‭the TSH receptor‬
‭●‬ ‭T3 and T4 are‬‭low‬
‭●‬ ‭Hyperthyroidism with‬‭peculiar edema behind the eyes‬‭called‬‭exolphthalmos‬
‭●‬ ‭TSH is‬‭low‬
‭which causes the eye to protrude‬
‭●‬ ‭Hypersecretion of thyroid stimulating immunoglobulins (TSIs)‬ ‭Congenital Hypothyroidism/Cretinism‬
‭●‬ ‭Diagnostic test: TSH receptor antibody test‬ ‭●‬ ‭Hypersecretion of thyroid hormone during fetal/infancy life‬
‭Riedel’s Thyroiditis‬ ‭○‬ ‭Iodine deficiency‬
‭●‬ ‭Defects in the development or function of the gland‬
‭●‬ ‭Thyroid turns into‬‭woody or stony hard mass‬
‭●‬ ‭Physical and mental development of the child are retarded‬
‭Subclinical Hyperthyroidism‬
‭●‬ ‭Screening test:‬‭T4 (decreased)‬
‭●‬ ‭No clinical symptoms‬
‭●‬ ‭Confirmatory:‬‭TSH (increased‬‭)‬
‭●‬ ‭TSH is‬‭low‬
‭○‬ ‭Specifically congenital if its occurs in fetal life or infancy period‬
‭●‬ ‭FT3 and FT4 are‬‭normal‬
‭Subclinical Hypothyroidism‬
‭Subacute granulomatous thyroiditis‬
‭●‬ ‭T3 and T4‬‭normal‬
‭●‬ ‭Associated with neck pain, low grade fever, and swings in thyroid function tests‬
‭●‬ ‭TSH is slightly‬‭increased‬
‭●‬ ‭Thyroidal peroxidase (TPO‬‭) antibodies are‬‭absent‬
‭Goiter‬
‭●‬ ‭ESR and thyroglobulin levels are‬‭elevated‬
‭●‬ ‭an‬‭enlarged thyroid gland‬‭which is a‬‭symptom of many‬‭thyroid disorders‬
‭Hypothyroidism‬
‭(hypo, hyper, or euthyroid state)‬
‭●‬ ‭Define as a low FT4 level with a normal or high TSH level‬
‭Laboratory Measurement of Some Hormones Secreted by the Thyroid Gland‬
‭●‬ ‭One of the most common disorder of the thyroid gland‬
‭●‬ ‭Develops whenever‬‭insufficient‬‭amounts of thyroid‬‭hormone are available to‬
‭tissues‬ ‭Serum Free Triiodothyronine‬
‭●‬ ‭Treated with thyroid hormone replacement therapy (levothyroxine)‬ ‭‬ m
● ‭ easures the amount of‬‭free triiodothyronine (T3)‬‭in blood‬
‭Signs and Symptoms‬ ‭●‬ ‭used to evaluate and manage disorders of the thyroid gland‬
‭●‬ ‭Bradychardia‬ ‭●‬ ‭related tests: TSH, FT4‬
‭●‬ ‭Weight Gain‬ ‭○‬ ‭Adults:‬‭1.4-4.4 pg/mL (0.22-6.78 pmol/L)‬
‭●‬ ‭Coarsened skin‬ ‭○‬ ‭N>37 weeks (cord blood): 15-391 pg/dL (0.2-6 pmol/L)‬
‭●‬ ‭Cold intolerance‬ ‭○‬ ‭Pregnancy, 1st: 211-383 pg/dL (3.2-5.9 pmol/L)‬
‭●‬ ‭Mental dullness‬ ‭○‬ ‭Pregnancy, 2nd: 196-338 pg/dL (3-5.2 pmol/L)‬
‭○‬ ‭Pregnancy, 3rd: 196-338 pg/dL (3-5.2 pmol/L)‬
‭SIGNS‬ ‭SYMPTOMS‬
‭Delayed relaxation phase of deep tendon‬ ‭Cold intolerance‬ ‭Direct Equilibrium Dialysis‬
‭reflex testing‬ ‭‬ u
● ‭ ses undiluted serum dialyzed for 16-18 hours at 37°C‬
‭Bradycardia‬ ‭Depression‬ ‭●‬ ‭dialysate is then analyzed directly using RIA‬
‭Diastolic hypertension‬ ‭Mental retardation (infants), slowed‬ ‭○‬ ‭2-128 ng/L (2.6 to 165 pmol/L)‬
‭cognition‬ ‭Ultracentrifugation‬
‭Coarsened skin, yellowing of skin‬ ‭Menorrhagia‬
‭‬
● ‭ erum is adjusted to pH of 7.4‬
s
‭(carotenemia)‬
‭Periorbital edema‬ ‭Growth failure (children)‬ ‭●‬ ‭incubated for 20 minutes at 37°C‬
‭Thinning of eyebrows/loss of lateral‬ ‭Pubertal delay‬ ‭●‬ ‭ultracentrifuge for 30 minutes at 37°C and 2000 rpm‬
‭aspect of brows‬ ‭●‬ ‭ultrafiltrate is analyzed by immunoassay‬
‭Slowed movement/speech‬ ‭Dry skin‬ ‭●‬ ‭less time consuming than dialysis‬
‭Pleural/pericardial effusion‬ ‭Edema‬ ‭Triiodothyronine Measurement‬
‭Ascites‬ ‭Constipation‬ ‭‬ m
● ‭ easures the level of‬‭total T3 in blood‬
‭Dyspnea on exertion‬ ‭●‬ ‭used to‬‭evaluate and manage thyroid dysfunction, including‬
‭hyperthyroidism‬
‭Primary Hypothyroidism‬ ‭●‬ ‭related tests: FT4, T3 uptake‬
‭‬
● ‭ ue to‬‭deficiency‬‭of elemental‬‭iodine‬
D ‭○‬ ‭Adults: 60-181 ng/dL (0.92-2.78 nmol/L)‬
‭●‬ ‭Decreased‬‭T3 and T4,‬‭increased‬‭TSH‬ ‭○‬ ‭Pregnancy (last 5 mos): 116-247 ng/dL (1.79-3.8 nmol/L)‬
‭●‬ ‭Caused by destruction or ablation of the thyroid gland‬ ‭Serum Total T4 Competitive Immunoassay‬
‭●‬ ‭Other causes:‬ ‭●‬ m ‭ easures the‬‭total amount of thyroxine/T4 (both free‬‭and CHON bound)‬‭in‬
‭○‬ ‭Surgical removal of the gland‬ ‭blood‬
‭○‬ ‭Used of radioactive iodine for hyperthyroidism treatment‬ ‭●‬ ‭uses‬‭barbital buffers‬‭(vs TBPA) and‬‭8-anilino-1-naphthalene-sulfonic‬‭acid‬‭(vs‬
‭○‬ ‭Radiation exposure‬ ‭TBG)‬
‭○‬ ‭Drugs such as lithium‬ ‭○‬ ‭Adults: 4.5-10.9 μg/dL (58-140 nmol/L)‬
‭TSH Immunoassay‬ ‭9.‬ ‭Thyroxine Binding Globulin (TBG) Test‬
‭●‬ M ‭ ost important thyroid function test‬ ‭ 0.‬ ‭Fine Needle Aspiration‬
1
‭○‬ ‭Best screening test‬ ‭11.‬ ‭Recombinant Human TSH‬
‭○‬ ‭Help in early detection of hypothyroidism‬ ‭12.‬ ‭Tanned Erythrocyte Hemagglutination Test‬
‭○‬ ‭most clinically sensitive immunoassay used for the detection primary thyroid‬ ‭13.‬ ‭Serum Calcitonin Test‬
‭disorder‬ ‭Summary: Thyroid Function Tests‬
‭●‬ ‭measures the amount of thyroid stimulating hormone (TSH) in blood‬
‭●‬ ‭using‬‭chemiluminescence w/ low detection limit‬ ‭Disorders‬ ‭T3‬ ‭T4‬ ‭TSH‬ ‭FT4‬ ‭rT3‬ ‭Tg‬ ‭TBG‬
‭●‬ ‭TSH test can be used to differentiate the primary from secondary‬ ‭Grave’s Disease‬ ↑‭ ‬ ‭↑‬ ↓‭ ‬ ↑‭ ‬ ‭‬
↑ ‭↑‬ ‭N‬
‭hypothyroidism‬ ‭Primary Hypothyroidism‬
‭○‬ ‭Monitor and adjust thyroid hormone replacement therapy‬
‭↓/‬‭N‬ ‭↓‬ ‭↑‬ ‭↓‬ ‭↓‬ ↓ ‭ /‬‭N‬ ‭N‬

‭●‬ ‭related tests: T3 and T4‬ ‭Hashimoto Thyroiditis‬ ‭↓/‬‭N‬ ↓‭ /‬‭N‬ ‭↑‬ ‭N/‬‭↓‬ ‭↓‬ ‭N/‬↓ ‭‬ ‭N‬
‭○‬ ‭Adults: 0.5-4.7 μunits/L‬ ‭Nonthyroidal illness‬ ‭↓‬ ‭N/‬↓‭ ‬ ‭V‬ ‭V‬ ‭N/‬‭↑‬ ‭N‬ ‭N‬
‭○‬ ‭Pregnancy (1st): 0.3-4.5 μunits/L‬ ‭ hyroid Hormone‬
T
‭○‬ ‭Pregnancy (2nd): 0.5-4.6 μL‬ ‭Resistance‬ ‭↑‬ ‭↑‬ ‭N/‬‭↑‬ ‭↑‬ ‭↑‬ ‭↑‬ ‭N‬
‭○‬ ‭Pregnancy (3rd): 0.8-5.2 μL‬
‭TSH Immunoassay‬ ‭PARATHYROID GLAND‬
‭●‬ S ‭ econd-Generation TSH Immunometric Assays‬ ‭●‬ ‭Located near the thyroid capsule,‬
‭○‬ ‭with detection limits of 0.1 mU/L‬ ‭○‬ ‭sometime within the thyroid gland‬
‭○‬ ‭screen for hyperthyroidism‬ ‭○‬ ‭Most of the people they have four parathyroid gland but in some they have‬
‭●‬ ‭Third-generation TSH chemiluminometric assays‬ ‭eight or as few as two‬
‭○‬ ‭with detection limits of 0.01 mU/L, (euthyroidism and hyperthyroidism)‬ ‭○‬ ‭Secrete PTH‬
‭○‬ ‭routinely used to monitor and adjust thyroid hormone replacement therapy‬ ‭●‬ ‭Samples endocrine gland in the body‬
‭○‬ ‭screen both hyperthyroidism and hypothyroidism.‬ ‭●‬ ‭four tiny glands attached to the thyroid‬
‭○‬ ‭The sensitivity of this has lead to the ability to detect what is turned‬ ‭●‬ ‭releases PTH‬
‭subclinical disease or the mild degree of thyroid dysfunction‬ ‭○‬ ‭The primary role of the PTH is to prevent hypocalcemia‬
‭Increased TSH‬ ‭Decreased TSH‬ ‭○‬ ‭It regulates the blood calcium‬
‭Primary Hypothyroidism‬ ‭Primary Hyperthyroidism‬ ‭○‬ ‭Preserve calcium and phosphate within the normal range‬
‭Hashimoto’s Thyroiditis‬ ‭Secondary and Tertiary Hypothyroidism‬ ‭○‬ ‭Promotes bone resorption → release calcium into the bloodstream‬
‭Thyrotoxicosis due to Pituitary Tumor‬ ‭Treated Grave’s Disease‬ ‭○‬ ‭PTH also increased renal reabsorption of calcium‬
‭TSH Antibodies‬ ‭Euthyroid Sick Disease‬ ‭○‬ ‭Stimulate the conversion of inactive vitamin D to vitamin D3‬
‭Thyroid Hormone Resistance‬ ‭Over Replacement Hormone in‬ ‭○‬ ‭actions directed to bone, kidney and intestines‬
‭Hypothyroidism‬ ‭○‬ ‭controls calcium and phosphate metabolism with the help of calcitonin‬
‭Types of cells:‬
‭Anti-TSH Receptor Autoantibody‬
‭●‬ ‭Chief cells‬
‭ ‬ f‭or diagnosis of‬‭Grave’s disease‬
● ‭○‬ ‭synthesize and secrete hormone PTH‬
‭●‬ ‭detects autoantibodies that interfere with the binding of TSH to TSH receptor‬ ‭●‬ ‭Oxyphil cells‬
‭‬ s
● ‭ erum + TSH receptor + I‬‭125‬ ‭labelled TSHtracer‬ ‭○‬ ‭non secretory cell‬
‭●‬ ‭amount of free tracer is measured‬ ‭○‬ ‭seen only after puberty‬
‭○‬ ‭lower than 9 U/L‬ ‭DISEASES ASSOCIATED WITH HORMONES OF THE PARATHYROID GLAND‬
‭Thyrotropin Releasing Hormone (TRH) Stimulation Test‬
‭ ‬ I‭t measure the relationship between TRH and TSH secretion‬
● ‭Hyperparathyroidism‬
‭●‬ ‭Used to differentiate euthyroid and hyperthyroid patient who both had‬
‭undetectable TSH level‬ ‭Primary Hyperparathyroidism‬
‭●‬ ‭Also be helpful in the detection of the thyroid hormones resistance‬ ‭●‬ ‭Physiologic defect lies with the‬‭Parathyroid gland‬
‭syndrome‬ ‭●‬ ‭Most common cause‬‭of hypercalcemia‬
‭●‬ ‭injection of TRH and measurement of the output of TSH‬ ‭●‬ ‭Is due to the presence of a functioning‬‭parathyroid‬‭adenoma‬
‭○‬ ‭Dose needed TRH: 500 ug by IV‬ ‭●‬ ‭Is accompanied with‬‭phosphaturia‬
‭○‬ ‭Increase: primary hypothyroidism‬ ‭●‬ ‭If it goes undetected,‬‭severe demineralization‬‭may‬‭occur (osteitis fibrosa‬
‭○‬ ‭Decrease: hyperthyroidism‬ ‭cystica)‬
‭●‬ ‭used in the diagnosis of combined pituitary- thyroid disorders‬ ‭●‬ ‭Lab Results:‬
‭●‬ ‭differentiates 2° hypothyroidism and 3°hypothyroidism‬ ‭○‬ ‭PTH increased‬
‭Other Laboratory Tests:‬ ‭○‬ ‭Ionized Ca increased‬
‭●‬ ‭Radioactive iodine (RAI) uptake:‬ ‭○‬ ‭Hypercalciuria‬
‭○‬ ‭based on the ability of the thyroid to concentrate, convert and release4 I‬‭2‬ ‭○‬ ‭Hypophosphatemia (fasting state)‬
‭○‬ ‭Used to measure the ability of the thyroid gland to trap iodine‬ ‭Secondary Hyperparathyroidism‬
‭○‬ ‭Helpful in establishing the cause of hyperthyroidism‬ ‭●‬ ‭Develops in response to decrease serum calcium‬
‭○‬ ‭High uptake = indicates that there is metabolically active hormone +‬ ‭●‬ ‭There is‬‭diffuse hyperplasia‬‭of all 4 glands‬
‭Low or TSH deficiency = autonomous thyroid activity‬ ‭●‬ ‭The patient develops severe‬‭bone disease‬
‭●‬ ‭Thyroid Blocking Immunoglobulin (TBI):‬ ‭●‬ ‭Causes:‬‭vit. D deficiency and chronic renal failure‬
‭○‬ ‭based on the thyroid hormone transport system indirectly measuring the‬ ‭●‬ ‭Lab results:‬
‭amount of TBG‬ ‭○‬ ‭PTH increased‬
‭●‬ ‭Protein Bound Iodine Test (PBI):‬ ‭○‬ ‭Ionized calcium decreased‬
‭○‬ ‭based on thyroid hormone concentration representing the organic fraction‬ ‭Tertiary Hyperparathyroidism‬
‭of blood iodine that precipitates with serum proteins‬
‭●‬ ‭It‬‭occurs‬‭with‬‭secondary hyperparathyroidism‬
‭○‬ ‭A laboratory test that indirectly assesses the thyroid function by‬
‭●‬ ‭Develops autonomous function of the hyperplastic parathyroid glands‬‭or of‬
‭measuring the concentration of iodine bound to proteins circulating in the‬
‭parathyroid adenoma‬
‭bloodstream‬
‭●‬ ‭The phosphate levels are normal to high;‬‭Calcium phosphates‬‭precipitates in‬
‭●‬ ‭Basal Metabolic Rate (BMR):‬
‭soft tissues‬
‭○‬ ‭based on metabolic response measuring the O2 consumption in the‬
‭Hypoparathyroidism‬
‭resting fasting state‬
‭●‬ ‭Is due to‬‭accidental injury to the parathyroid glands‬‭(neck) during surgery-‬
‭Summary: Thyroid Function Tests‬
‭post-surgical cause‬
‭1.‬ ‭TRH Stimulation Test‬
‭●‬ ‭Other cause:‬‭autoimmune‬‭parathyroid destruction‬
‭2.‬ ‭TSH Test‬
‭●‬ ‭Individual are unable to maintain calcium concentration in the blood without‬
‭3.‬ ‭Radioactive Iodine Uptake (RAIU)‬
‭calcium supplementation‬
‭4.‬ ‭Thyglobulin (Tg) assay‬
‭●‬ ‭In hypoparathyroidism, the distal convoluted tubules reabsorbs‬‭bicarbonate as‬
‭5.‬ ‭Reverse T3 (rT3)‬
‭well as phosphate‬‭resulting in acidosis‬
‭6.‬ ‭Free Thyroxine Index (FT4I or T7)‬
‭●‬ ‭PTH normally interferes with bicarbonate reabsorption in the PCT; therefore, the‬
‭7.‬ ‭Total T3 (TT3), FT3, FT4‬
‭renal tubular bicarbonate threshold tends to be in increased in‬
‭8.‬ ‭T3 Uptake Test‬
‭hypoparathyroidism‬
‭‬ L
● ‭ ow PTH causes elevated bicarbonate reabsorption-alkalosis‬ ‭Glucagon Immunoassay (RIA)‬
‭●‬ ‭The best method for PTH measurement involves the use of‬‭antibodies that‬ ‭125‬
‭●‬ ‭glucagon competes with‬ ‭I tracer for binding sites‬
‭detect both the amino terminal fragment and intact PTH‬
‭125‬
‭Laboratory method for PTH:‬ ‭●‬ a ‭ mount of‬ ‭I is measured and is inversely proportional‬‭to the concentration of‬
‭●‬ ‭PTH level measurement:‬ ‭glucagon‬
‭○‬ ‭overnight fasting‬ ‭●‬ ‭Fasting: 60-200 pg/mL‬
‭■‬ ‭Intact PTH: 10-65 pg/mL‬
‭■‬ ‭PTH N-terminal (includes intact PTH): 8-24 pg/mL‬
‭■‬ ‭PTH C-terminal (includes C-terminal, intact PTH, and midmolecule):‬
‭50-330 pg/mL‬
‭●‬ ‭related tests: Calcium, Phosphorus and Creatinine‬
‭Pancreas‬
‭●‬ ‭Organ located in the abdomen‬
‭●‬ ‭Essential role: converting food into fuel for the body's cell‬
‭●‬ ‭Two main function‬
‭○‬ ‭Exocrine organ – that help indigestion‬
‭○‬ ‭Endocrine – regulate blood sugar‬
‭●‬ ‭lying immediately beneath the stomach‬
‭●‬ ‭both an exocrine and an endocrine gland‬
‭Types of tissues:‬
‭●‬ ‭Acini‬
‭○‬ ‭secretes digestive juices into the intestine‬
‭●‬ ‭Islets of Langerhans‬
‭○‬ ‭secretes hormones directly into the blood‬
‭Hormones in Pancreas‬
‭●‬ ‭Glucagon: glycogenolysis and gluconeogenesis‬
‭●‬ ‭Insulin: glycogenesis, glycolysis, lipogenesis‬
‭●‬ ‭Somatostatin‬
‭DISEASES ASSOCIATED WITH HORMONES OF THE PANCREAS‬

‭Diabetes mellitus‬
‭‬ d
● ‭ ‭e ‬ ficiency of insulin or defects in insulin receptors‬
‭●‬ ‭Increase in blood glucose level‬
‭●‬ ‭Causes: due to stress, severe infection, dehydration or pregnancy,‬
‭pancreatectomy, haemochromatosis‬
‭●‬ ‭FBS – high >126 mL/d‬
‭Hyperinsulinism‬
‭●‬ ‭It refers to above normal level of insulin in the blood of a patient‬
‭○‬ ‭The secretion of insulin are closely related to the level of glucose in the blood‬
‭○‬ ‭The insulin of an individual is maybe normal but it can be low or high to‬
‭another individual‬
‭❖‬ ‭The secretion is depend on level of the blood glucose of the individual in‬
‭the body‬
‭❖‬ ‭For a certain individual we should check what is the normal level of‬
‭his/her insulin before it considered that there is hyperinsulinism‬
‭●‬ ‭hypersecretion of insulin‬
‭○‬ ‭Insulin is the primary hormone responsible for the entry of glucose in the cell‬
‭❖‬ ‭Hypoglycemic agent → release by beta cell‬
‭●‬ ‭may be due to a tumor, insulinoma‬
‭Glucagonoma‬
‭●‬ ‭hypersecretion of glucagon by a tumor‬
‭○‬ ‭Glucagon is a primary hormone responsible for an increase in glucose level‬
‭○‬ ‭It is a hyperglycemic agent → alpha cell → release during stress and fasting‬
‭state‬
‭○‬ ‭Work with insulin to control the amount of sugar in the blood‬
‭○‬ ‭If there is an tumor they produced large amount of glucagon‬
‭○‬ ‭If high levels continuously it can create severe and life-threatening symptoms‬
‭Somatostatinoma‬
‭●‬ ‭hypersecretion of somatostatin by a tumor‬
‭●‬ ‭Somatostatin which is produced by delta cells‬
‭○‬ ‭Inhibits the action of insulin and glucagon‬
‭Laboratory Measurement of some hormones secreted by the Pancreas‬

‭Insulin C-peptide Measurement‬


‭●‬ ‭measures the level of a by-product of the hormone insulin called‬‭C-peptide in‬
‭blood‬
‭●‬ ‭used to know how much insulin is being produced in the body‬
‭●‬ ‭fasting specimen‬
‭○‬ ‭Adults: 0.5 - 2.0 ng/mL (0.17 - 0.66 nmol/L)‬
‭Anti-Insulin Antibody Test(RIA)‬
‭●‬ ‭measures the amount of‬‭antibodies to insulin‬
‭●‬ ‭used when insulin resistance in diabetes is suspected‬
‭●‬ ‭determination of the binding of 125I-Tyr-Al4-insulin to the serum fraction‬
‭precipitated by PEG‬
‭●‬ ‭related test: Insulin C-peptide‬
‭○‬ ‭<8.2% binding‬
‭MID-LECT5-ENDOCRINOLOGY 3‬
‭Hormones Produced by the Adrenal Glands‬
‭●‬ ‭Adrenal glands – also known as suprarenal glands‬
‭○‬ ‭Small, triangular-shaped glands ;located on top of the kidneys‬
‭○‬ ‭Right and left adrenal gland‬
‭○‬ ‭Produced steroid hormones and neuropeptide that help regulates metabolism,‬
‭immune system, blood pressure and the responds to stress and other‬
‭essentials function‬
‭Adrenal Glands‬
‭●‬ ‭pyramid-like shaped located above the kidneys‬
‭●‬ ‭Composed of distinct but conjoined glands, the‬‭outer adrenal cortex‬‭(‬‭yellow‬‭)‬
‭and the‬‭inner adrenal medulla‬‭(‬‭dark mahogany‬‭)‬ ‭The conversion of cholesterol to pregnenolone will happen with the help of CYP 450‬
‭○‬ ‭Cortex - include the mesenchymal cells‬
‭■‬ ‭Differentiated into three structurally and functionally distinct zone‬
‭❖‬ ‭zona glomerulosa‬
‭➢‬‭Mineralocorticoids, aldosterone (for sodium retention, potassium‬
‭and acid-base homeostasis)‬
‭❖‬ ‭zona fasciculata‬
‭➢‬‭Glucocorticoids, cortisol and corticortesone‬
‭❖‬ ‭zona reticularis‬
‭➢‬‭Sulfate, DHEA, DHEAS‬
‭○‬ ‭Medulla - contain neural-crest cells‬
‭●‬ ‭It has prime effects on blood pressure‬

‭ ake note: after the cholesterol was converted into pregnenolone you will now have‬
T
‭here the different hormones‬
‭Cortisol‬
‭●‬ ‭Principal‬‭glucocorticoid‬
‭●‬ ‭Synthesis is regulated by‬‭ACTH‬
‭●‬ ‭Critical to hemodynamic and glucose-homeostasis‬
‭○‬ ‭The glucocorticoids they maintain blood glucose by inducing lipolysis and‬
‭gluconeogenesis‬
‭○‬ ‭They have anti-inflammatory and immunosuppressive action‬
‭Hormones‬ ‭●‬ ‭Mostly bound to glycoprotein‬‭(transcortin)‬
‭Adrenal Cortex‬ ‭Adrenal Medulla‬ ‭●‬ ‭Stimulates‬‭lipolysis and gluconeogenesis‬‭in the liver‬
‭●‬ ‭The only adrenal hormone that‬‭inhibits‬‭the secretion of ACTH**‬
‭Cortisol‬ ‭Norepinephrine‬
‭●‬ ‭Therapeutic agent for‬‭RA, SLE, MS**‬
‭Aldosterone‬ ‭Epinephrine‬
‭●‬ ‭Secretion is diurnal‬‭and is associated with sleep-wake‬‭cycle (highest at 8-9am‬
‭Weak androgens‬ ‭Dopamine‬
‭and lowest 10pm-12am)‬

‭Adrenal Cortex‬
‭●‬ ‭Major site of steroids hormone production‬
‭○‬ ‭Cholesterol is the parent cell of all steroids hormones‬
‭●‬ ‭The outer region of the adrenal gland secreting the‬‭steroid hormone‬
‭●‬ ‭The secretion of adrenal glucocorticoids and androgens is regulated by‬
‭Adrenocorticotropic hormone (ACTH)‬‭, which is under the control of the‬
‭hypothalamic‬‭corticotropin-releasing hormone‬‭(CRH)‬
‭●‬ ‭Mineralocorticoids‬‭secretion is controlled by the‬‭RAAS‬
‭●‬ ‭Cortical hormones are composed of CPPP‬‭(cyclopentanoperhydrophenanthrene)‬
‭3 Layers of Adrenal Cortex‬
‭1.‬ ‭Zona Glomerulosa‬‭(outermost layer)- 10%‬
‭○‬ ‭Principal source of mineralocorticoids‬ ‭ he cortisol can be found or released in the F-zone, In the F-zone the main steroid is‬
T
‭■‬ ‭Salt regulation‬ ‭the cortisol and the regulator is the ACTH. the function is for blood pressure and‬
‭2.‬ ‭Zona Fasciculata‬‭(middlemost layer) -75%‬ ‭glucose homeostasis‬
‭○‬ ‭Site of glucocorticoid synthesis‬ ‭Syndrome:‬
‭○‬ ‭Also synthesize unsulfated DHEA‬ ‭Low cortisol → adrenal insufficiency → symptoms: hypotension, hypoglycemia,‬
‭3.‬ ‭Zona Reticularis‬‭(innermost layer) -15%‬ ‭weight loss, weakness‬
‭○‬ ‭Produces androstenedione and dehydroepiandrosterone (weak androgens)‬ ‭Increase cortisol → hypercortisolism → symptoms: hypertension, hyperglycemia,‬
‭3 Layers of Adrenal Cortex‬ ‭central obesity, weakness‬
‭●‬ ‭Aldosterone‬
‭○‬ ‭low cytoplasm to nuclear ratio and small nuclei with‬‭dense chromatin‬‭with‬
‭intermediate lipid inclusions.‬
‭●‬ ‭Cortisol-‬
‭○‬ ‭high cytoplasm to nuclear ratio, lipid laden with‬‭“foamy”‬‭cytoplasm.‬
‭●‬ ‭DHEAS‬
‭○‬ ‭lipid deficient but‬‭has lipofuscin‬‭deposit sharply demarcated cells‬
‭For the measurement of aldosterone‬ ‭Adrenal Insufficiency‬
‭●‬ ‭Serum, plasma, saliva and urine may be used,‬ ‭●‬ L ‭ ow baseline cortisol levels (8:00 am, supine) and an elevated ACTH greater‬
‭○‬ ‭blood samples should be drawn at‬‭8 am‬ ‭than 200 pg/mL‬‭(PRIMARY)‬
‭●‬ ‭Urine free cortisol‬‭levels are sensitive indicators of adrenal hyperfunction‬ ‭●‬ ‭Lower serum concentrations of ACTH and cortisol‬‭(SECONDARY)‬
‭(endogenous corticolism-‬‭24 hour urine collection‬‭)‬ ‭○‬ ‭Usually suggested in patient who have near normal response in cosyntropin‬
‭Urinary Metabolites‬ ‭test 200 pg/mL but abnormal response to metyrapone test‬
‭●‬ ‭The liver degrades all glucocorticoids to metabolites excreted in urine‬ ‭Cosyntropin Test‬
‭1.‬ ‭17-hydroxycorticosteroid‬ ‭●‬ ‭determines the capacity of the adrenal gland to increase hormone production in‬
‭●‬ ‭Measured by‬‭Porter-Silber Method‬ ‭response to stimulation.‬
‭●‬ ‭Reagents: Phenylhydrazine in H2SO4 + acohol‬ ‭Metyrapone Test‬
‭2.‬ ‭17-ketogenic steroids‬ ‭●‬ ‭block 11β-hydroxylase, increasing 11-deoxycortisol (>7 μg/dL) while cortisol‬
‭●‬ ‭Measured by‬‭Zimmermann Reaction‬‭(reddish purple)‬ ‭decreases (<5 μg/dL).‬
‭●‬ ‭Reagent: Meta-dinitrobenzene‬ ‭In both test there will be synthetic stimulator of cortisol and aldosterone secretion that‬
‭●‬ ‭Oxidation Procedure: Norymberski (Na bismuthate)‬ ‭will be given‬
‭Clinical Disorders‬ ‭Primary Hypocortisolism‬
‭●‬ ‭Hypercortisolism‬ ‭●‬ ‭Due to decreased cortisol production- 90% destruction of the adrenal cortex;‬
‭●‬ ‭Hypocortisolism‬ ‭aldosterone deficiency; excess ACTH release‬
‭○‬ ‭Primary Hypocortisolism‬ ‭Disorder:‬
‭○‬ ‭Secondary Hypocortisolism‬ ‭Addison’s Disease‬
‭●‬ ‭Congenital Adrenal Hyperplasia‬ ‭○‬ ‭Hypotension, hyponatremia, hyperkalemia, weight loss, hyperpigmentation)‬
‭○‬ ‭21-hydroxylase deficiency‬ ‭○‬ ‭Due to autoimmune adrenalitis, tuberculosis, hemorrhage, HIV/AIDS infection‬
‭○‬ ‭11ß-hydroxylase deficiency‬ ‭Screening Test:‬
‭○‬ ‭3ß-hydroxysteroid dehydrogenase isomerase deficiency‬ ‭○‬ ‭ACTH Stimulation Test‬
‭○‬ ‭C-17,20-lyase/ 17α-hydroxilase deficiency‬ ‭■‬ ‭Increased ACTH and decreased cortisol and aldosterone‬
‭Hypercortisolism‬ ‭Secondary Hypocortisolism‬
‭●‬ ‭Also known as the‬‭secondary adrenal insufficiency‬
‭Cushing’s Syndrome‬ ‭●‬ ‭Due to hypothalamic-pituitary insufficiency with loss of‬‭ACTH‬
‭●‬ ‭Primarily caused by excessive production of‬‭cortisol and ACTH‬ ‭●‬ ‭No problem with mineralocorticoid secretion;‬‭absence of hyperpigmentation‬
‭●‬ ‭Caused by overuse of‬‭corticosteroid‬ ‭●‬ ‭Lab Test:‬‭ACTH Stimulation Test‬
‭Signs and Symptoms:‬ ‭○‬ ‭(+) result- delayed in response to stimulation test.‬
‭●‬ ‭Weight gain but with thin extremities‬‭“buffalo hump”‬‭, hyperglycemia, thinning of‬ ‭○‬ ‭Decreased ACTH and cortisol‬
‭the skin, poor wound healing, hypertension, hypercholesterolemia, decreased‬ ‭Procedure of ACTH Stimulation Test‬
‭WBC‬ ‭●‬ ‭Also known as‬‭Cosyntropin Stimulation Test‬
‭Screening Test‬ ‭●‬ ‭Also differentiates secondary adrenal insufficiency (decreased or no ACTH‬
‭●‬ ‭24 hour urinary free cortisol (inc >120 ug/day)‬ ‭response) from tertiary adrenal insufficiency (increased ACTH response)‬
‭●‬ ‭Overnight dexamethasone suppression test-‬‭most widely used salivary‬ ‭○‬ ‭stimulation test that can be used to distinguished hypothalamic or tertiary‬
‭cortisol‬ ‭adrenal insufficiency and pituitary or secondary adrenal insufficiency‬
‭Confirmatory Test‬ ‭●‬ ‭Cosyntropin is a synthetic cortisol and aldosterone stimulator‬
‭●‬ ‭Low-dose dexamethasone suppression test-‬ ‭●‬ ‭It requires administration of‬‭250 ug‬‭of Cosyntropin IV or IM‬
‭●‬ ‭Midnight plasma cortisol (> 5.0 ug/dL)‬ ‭Metyrapone Test‬
‭●‬ ‭CRH stimulation test‬ ‭●‬ ‭Measures the ability of the pituitary gland to respond to declining levels of‬
‭circulating cortisol, thereby secretes ACTH‬
‭●‬ ‭Is used as an alternative diagnostic or confirmatory test for‬‭tertiary adrenal‬
‭insufficiency‬
‭●‬ ‭500 to 750 mg of metyrapone is orally administered every 4 hours for 24 hours‬
‭●‬ ‭Performed only if the ACTH stimulation test gives normal result‬
‭●‬ ‭(+) result: decreased ACTH‬‭(24 hour urine)‬
‭●‬ ‭Metyrapone is an inhibitor of 11-beta hydroxylase‬
‭Things to consider:‬
‭●‬ ‭24 hour urine free cortisol‬‭is the‬‭most sensitive and specific screening test‬
‭f‭o ‬ r excess cortisol production using HPLC or GC-MS- because plasma cortisol is‬
‭affected by diurnal variation‬
‭●‬ ‭Urinary free cortisol‬‭is the‬‭only portion‬‭of cortisol that‬‭passes through‬
‭glomerular filtration‬
‭●‬ ‭HPLC-MS‬‭- the current reference method for measuring urinary free cortisol‬
‭●‬ ‭Insulin Tolerance test‬‭is the‬‭gold standard for secondary and tertiary‬
‭hypocorticolism‬‭, confirms borderline response to ACTH stimulation‬
‭Standard assessment tests for diagnosing Cushing’s syndrome‬
‭Determine Loss of Normal Cortisol Suppression by Dexamethasone‬
‭●‬ ‭Use of Dexamethasone‬
‭○‬ ‭Act as exogenous cortisol substitute‬
‭○‬ ‭Suppress the ACTH‬
‭■‬ ‭If the pituitary gland is normal and cortisol if the adrenal gland is normal‬
‭●‬ ‭An overnight dexamethasone suppression test is commonly used to screen‬
‭patients for autonomous overproduction of cortisol‬
‭○‬
‭Test‬
‭●‬ P
‭ rocedure of‬‭Overnight / Rapid Dexamethasone suppression test‬
‭○‬ ‭1 mg of dexamethasone is orally given to patient between‬‭11pm to 12‬
‭midnight‬
‭○‬ ‭Blood is collected the following day‬‭8 am to 9 am‬‭and urine may be tested for‬
‭17 OHCS‬
‭○‬ ‭Normal patient w/o Cushing Syndrome has a cortisol value < 5 ug/dL and 17‬
‭OHCS of < 4mg.g creatinine after the test‬
‭○‬ ‭(+) result:‬‭all results not suppressed‬
‭●‬ ‭Procedure for Low - Dose Dexamethasone suppression test‬
‭○‬ ‭0.5 mg oral dexamethasone every‬‭6 hours for 2 days‬
‭○‬ ‭24 hour urine and serum samples are collected‬
‭○‬ ‭(+) result:‬‭elevated cortisol levels‬
‭Congenital Adrenal Hyperplasia‬ ‭Aldosterone‬
‭●‬ I‭t results from deficiency of enzymes such as‬‭21- hydroxylase deficiency, 11ß‬ ‭‬ M
● ‭ ajor‬‭electroregulating hormone‬
‭hydroxylase deficiency, 3ß hydroxysteroid dehydrogenase isomerase deficiency‬ ‭●‬ ‭Most potent‬‭mineralocorticoid‬
‭(necessary for the secretion of cortisol)‬ ‭●‬ ‭A‬‭steroid hormone‬‭that helps‬‭regulate water and electrolytes and blood‬
‭●‬ ‭This will result to‬‭decreased plasma cortisol, increased ACTH and increased‬ ‭levels‬‭(Na level in the serum depends almost completely on the interplay‬
‭levels of androgens‬ ‭between aldosterone and ADH‬
‭●‬ ‭24 hour urinary free cortisol is‬‭not consistent‬‭with‬‭CAH‬ ‭●‬ ‭Main determinant of renal excretion of potassium‬
‭Definitive Tests:‬ ‭●‬ ‭Acts on renal tubular epithelium to increase retention of Na and Cl, and excretion‬
‭●‬ ‭17-OHP measurement in amniotic fluid‬ ‭of K and H- promotes 1:1 exchange of Na for K or H‬
‭●‬ ‭Genotyping cells‬‭from chorionic villous s‬‭ampling-most preferred‬ ‭●‬ ‭The synthesis of this hormone is primarily controlled by the‬‭RAAS‬
‭●‬ ‭18-hydroxysteroid dehydrogenase‬‭- an enzyme needed for the synthesis of‬
‭aldosterone‬
‭●‬ ‭In G-zone‬
‭○‬ ‭The main steroid is the aldosterone‬
‭○‬ ‭Main regulator is the Renin-angiotensin aldosterone system (RAAS/RAS)‬
‭○‬ ‭Major function is blood pressure and potassium (K+) homeostasis‬
‭●‬ ‭Syndrome‬
‭○‬ ‭Decrease‬‭: Hypoaldosteronism (Distal RTA type IV)‬
‭■‬ ‭Clinical Finding‬‭: Hyperkalemia, renal salt wasting‬
‭○‬ ‭Increase:‬‭Hyperaldosteronism (aldosteronism)‬
‭■‬ ‭Clinical Finding:‬‭HTN, hypokalemia, metabolic alkalosis‬
‭Stimulators of aldosterone‬
‭●‬ ‭Angiotensin II, ACTH, elevated serum potassium‬
‭Inhibitors/Suppressor of Aldosterone‬
‭●‬ ‭progesterone and dopamine‬
‭●‬ ‭ANP, intracellular calcium, and certain drugs are aldosterone suppressors,‬
‭including ketoconazole, ACE inhibitors, nonsteroidal anti-inflammatory drugs, and‬
‭heparin‬

‭Remember the flow of the conversion and enzyme involved.‬

‭Enzyme Defect‬ ‭New Classification‬ ‭HTN‬ ‭Virilization‬ ‭High Lab Value‬


‭ B-Hydroxysteroid‬
3 ‭3B-HSD II‬ ‭N‬ ‭Slight‬ ‭DHEA‬
‭dehydrogenase‬
‭17a-Hydroxylase‬ ‭CYP17‬ ‭Y‬ ‭No‬ ‭Aldosterone‬
‭11B-Hydroxylase‬ ‭CYP11B1GF‬ ‭Y‬ ‭Marked‬ ‭11-DOC‬
‭21B-Hydroxylase‬ ‭CYP2jA2‬ ‭N‬ ‭Marked‬ ‭17-OH-progesterone‬
‭Figure: congenital adrenal hyperplasia syndromes‬
‭21-hydroxylase deficiency‬
‭●‬ ‭The most common form of‬‭CAH‬
‭●‬ ‭Elevated levels of‬‭17α-hydroxyprogesterone‬‭are indicative of this disorder and‬
‭urinary excretion of pregnanetriol‬
‭●‬ ‭Leads to‬‭hirsutism‬‭in women and other symptoms caused by e‬‭xcess androgen‬
‭levels‬‭such as v‬‭irilization; infertility and amenorrhea‬
‭●‬ ‭ACTH stimulation and (increase) 17a-hydroxyprogesterone tests‬‭are used‬
‭for testing‬
‭ ypes of aldosteronism according to Plasma Aldosterone PA:PRA Plasma Renin‬
T
‭●‬ ‭Hirsutism means there is an abnormal excessive growing of terminal hair‬
‭Activity ratio‬
‭commonly in females‬
‭●‬ ‭PA is low, PRA is low‬
‭○‬ ‭Meaning there is an androgens excess‬
‭○‬ ‭Salt retention, mineralocorticoid excess, glucocorticoid excess,‬
‭○‬ ‭Ferryman galway scale - Used to measure hirsutism‬
‭11B-Hydroxylase deficiency, Licorice ingestion, Liddle’s syndrome‬
‭■‬ ‭9 areas of assessment‬
‭●‬ ‭PA is high, PRA is low‬
‭➢‬‭(+) if the 8/9 areas are check to the assessment‬
‭○‬ ‭Gitelman’s syndrome (low Mg2), sympathetic activation (Pheo, drugs),‬
‭11ß hydroxylase deficiency‬ ‭bartter’s syndrome (low BP)‬
‭●‬ ‭The‬‭2nd most common‬‭form of CAH‬ ‭●‬ ‭PA is low, PRA is High‬
‭●‬ ‭Increased level of 11-deoxycortisol are indicative of this disorder‬ ‭○‬ ‭Hypokalemia, stress (hypoglycemia, trauma), upright posture, high renin HTN‬
‭●‬ ‭Associated with‬‭virilization and hypertension‬ ‭●‬ ‭PA is high, PRA is High‬
‭3ß hydroxysteroid dehydrogenase isomerase deficiency‬ ‭○‬ ‭Low effective blood volume, Renal artery stenosis, hepatorenal syndrome,‬
‭●‬ ‭Results to elevated ratio of‬‭17α-hydroxypregnenolone to 17α-‬ ‭renin-producing tumor, salt wasting (diuretics), fluid loss (blood loss, capillary‬
‭hydroxyprogesterone‬‭and increased ratio of‬‭DHEA to androstenedione‬ ‭leak)‬
‭●‬ ‭It is characterized by‬‭pseudohermaphrodism‬‭in female infants and incomplete‬ ‭Clinical Disorders‬
‭masculinization‬‭in male infants‬ ‭1.‬ ‭Primary Hyperaldosteronism (Conn’s Disease)‬
‭C-17,20-lyase/ 17α-hydroxylase deficiency‬ ‭2.‬ ‭Secondary Hyperaldosteronism‬
‭●‬ ‭Is characterized‬‭by inability‬‭to convert 17a- hydroxypregnenolone to DHEA and‬ ‭3.‬ ‭Hypoaldosteronism‬
‭17a-hydroxyprogesterone to androstenedione.‬ ‭4.‬ ‭Others:‬
‭●‬ ‭It will result to‬‭decrease androgen, cortisol, and estrogen synthesis;‬ ‭○‬ ‭Liddle’s Syndrome‬
‭decrease progesterone synthesis‬ ‭○‬ ‭Bartter’s Syndrome‬
‭●‬ ‭For females, absence of menstruation and defective ovarian maturation‬ ‭○‬ ‭Gitelman’s Syndrome‬
‭●‬ ‭For males, pseudohermaphrodis‬
‭Primary Hyperaldosteronism (Conn’s Disease)‬ ‭●‬ ‭Syndrome:‬
‭●‬ ‭Caused by‬‭aldosterone-secreting adrenal adenoma‬ ‭○‬ ‭Androgens excess‬
‭●‬ ‭Associated with‬‭elevated plasma aldosterone and low plasma renin‬ ‭■‬ ‭Symptoms: virilization in women and children. Gonadal‬
‭●‬ ‭In this condition, distal delivery of Na is increased because of increased NaCl‬ ‭dysfunction and infertility in men and women‬
‭reabsorption in the CD by the action of aldosterone inhibits salt reabsorption in‬ ‭■‬ ‭Virilization in men - penile enlargement, androgen dependent‬
‭the PCT as the result of volume expansion‬ ‭hair growth and secondary sexual characteristics‬
‭●‬ ‭Symptoms‬‭: hypertension, hypokalemia, mild hypernatremia and metabolic‬ ‭■‬ ‭Virilization in girls - develop hirsutism, acne and clitory megally‬
‭alkalosis‬
‭Screening Test:‬
‭●‬ ‭plasma aldosterone concentration / plasma renin activity ratio‬‭(PAC/PRA)‬
‭○‬ ‭(+) result:‬‭> 25 ratio‬
‭Confirmatory Test‬
‭●‬ ‭Saline Suppresion Test‬
‭○‬ ‭(+) result:‬‭> 5 ng/dL aldosterone‬
‭○‬ ‭Procedure for Saline Suppression Test‬
‭■‬ ‭Involves infusing 2 L of 0.9% saline over 4 hours, or by administering‬
‭10-12 mg NaCl tablet daily for 3 days‬
‭●‬ ‭Captopril suppression‬
‭○‬ ‭3 hours of taking 50 mg of captopril‬
‭○‬ ‭PA remains high if the patient have primary hyperalsoteronism‬
‭Secondary Hyperaldosteronism‬
‭●‬ ‭Occurs as a result of excessive production of‬‭renin‬
‭Adrenal Medulla‬
‭●‬ ‭Accompanied by elevated plasma levels of plasma levels of‬‭aldosterone‬
‭‬ C
● ‭ omposed primarily of chromaffin cells that secrete‬‭catecholamine‬
‭and renin‬
‭●‬ ‭L-tyrosines‬‭the precursor of the cathecolamines‬
‭●‬ ‭In this condition, hyperkalemia occurs only in conditions that are accompanied by‬
‭●‬ ‭Norepinephrine and epinephrine are metabolized by monoamine oxidase and‬
‭increased distal Na delivery‬
‭cathecol-0-methyl transferase to form metanephrines and VMA‬
‭●‬ ‭Secondary Hyperaldosteronism that result in hypokalemia:‬
‭●‬ ‭Ratio of norepinephrine to epinephrine in serum is‬‭9:1‬
‭○‬ ‭Renal artery stenosis, diuretic therapy, malignant hypertension, and‬
‭●‬ ‭The hormones are 50% protein bound‬
‭congenital defects inn renal salt transport such as Bartter’s Syndrome and‬
‭Hormones produced:‬
‭Gitelman’s Syndrome‬
‭●‬ ‭Norepinephrine‬
‭Liddle’s Syndrome (Pseudohyperaldosteronism)‬
‭●‬ ‭Epinephrine‬
‭●‬ ‭Congenital disorders that is characterized by‬‭increased ENaC activity‬‭in the‬ ‭●‬ ‭Dopamine‬
‭collecting ducts in the absence of increased aldosterone.‬
‭●‬ ‭Resemble primary aldosteronism clinically, but‬‭aldosterone level is low and‬
‭with absence of hypertension‬
‭Bartter’s Syndrome‬
‭●‬ ‭Bumetanide-sensitive chloride channel mutation‬
‭●‬ ‭A rare potassium-losing autosomal recessive disorder, caused by‬‭defective‬
‭NaCl reabsorption in the thick ALH‬
‭●‬ ‭Accompanied by‬‭elevated concentrations of aldosterone and renin‬
‭Gitelman’s Syndrome‬
‭●‬ ‭Thiazide sensitive transporter mutation‬
‭●‬ ‭Associated with the defect in NaCl reabsorption that occurs in the‬‭distal‬
‭convoluted tubule‬
‭●‬ ‭Accompanied by‬‭elevated aldosterone‬
‭Hypoaldosteronism‬
‭●‬ ‭Due to the destruction of the adrenal glands and deficiency of glucocorticoid‬
‭●‬ ‭Associated with enzyme‬‭21-hydroxylase deficiency‬
‭●‬ ‭Symptoms: hyperkalemia and metabolic acidosis‬ ‭○‬
‭Test:‬ ‭Norepinephrine‬
‭●‬ ‭Furosemide Stimulation Test or Upright Posture‬ ‭ ‬ ‭Primary amine‬

‭○‬ ‭(+) result: low aldosterone level‬ ‭●‬ ‭Produced by‬‭sympathetic ganglia‬
‭●‬ ‭Saline suppression Test‬ ‭●‬ ‭Highest concentration is found‬‭in‬‭brain‬
‭○‬ ‭(+) result: high aldosterone level‬ ‭●‬ ‭Acts as neurotransmitters in both CNS and sympathetic nervous system‬
‭Things to Consider:‬ ‭●‬ ‭Methoxy Hydroxyphenylglycol (MHPG)‬‭is the major metabolite in CNS‬
‭●‬ ‭Blood samples for aldosterone test should be‬‭drawn in the morning before the‬ ‭Major Metabolites:‬
‭patient has gotten out of bed‬‭- to avoid markedly increased result‬ ‭●‬ ‭3-methoxy-4-hydroxyphenylglycol (CSF and urine)‬
‭○‬ ‭Upright position for at least 2 hours before the collection‬ ‭●‬ ‭Vanellylmandelic acid (VMA)‬
‭○‬ ‭Avoid postural changes‬ ‭Norepinephrine‬
‭○‬ ‭Fasting is not required‬ ‭●‬ ‭Adrenaline/ secondary amine‬
‭●‬ ‭Plasma samples are treated with‬‭extraction agent to remove aldosterone from‬ ‭●‬ ‭Most abundant‬‭medullary hormone‬
‭plasma proteins‬ ‭●‬ ‭Produced from‬‭norepinephrine and comes only from the adrenal‬
‭●‬ ‭Urine samples are assayed using acid hydrolysis and extraction‬ ‭●‬ ‭Called the‬‭“fight or flight hormone”‬‭because it is released in response to‬
‭●‬ ‭Aldosterone levels are‬‭lower at night‬ ‭physiologic (injuries) and psychological (stress, anxiety) threats‬
‭●‬ ‭Florinef-‬‭synthetic mineralocorticoid‬ ‭●‬ ‭A form of stress that increases cortisol levels stimulates its production‬
‭●‬ ‭Methods for Aldosterone Measurement:‬‭RIA and Chromatography‬ ‭●‬ ‭Increases glucose concentration (glycogenolysis)‬
‭Weak Androgens‬ ‭●‬ ‭Best collected from‬‭indwelling catheter‬‭, since venipuncture‬‭may cause levels of‬
‭●‬ ‭Serves as precursor for the production of more potent‬‭androgens and‬ ‭cathecolamines to rise‬
‭estrogens‬‭in tissues‬ ‭●‬ ‭Major metabolites:‬‭VMA‬
‭●‬ ‭Produce as by-products of cortisol synthesis that are regulated by ACTH‬ ‭●‬ ‭Other urinary metabolites:‬
‭●‬ ‭Precursors:‬‭Pregnenolone and 17- hydroxypregnenolone‬ ‭○‬ ‭Metanephrines, normetanephrines, homovanillic acid‬
‭●‬ ‭E.G.‬‭Dehydryoepiandrosterone (DHEA) and androstenedione‬ ‭Dopamines‬
‭●‬ ‭DHEA‬‭- principal adrenal androgens is converted to‬‭estrone‬ ‭●‬ ‭Primary Amine‬
‭●‬ ‭They circulate bound to steroid hormone binding globulin (SHBG)‬ ‭●‬ ‭Major intact hormone in urine‬
‭●‬ ‭Excessive production of androgens results in virilization‬ ‭●‬ ‭A catecholamine produced in the body by the decarboxylation of 3,4‬
‭●‬ ‭Excessive production can be confirmed by measuring‬‭total and free‬ ‭dihydroxyphenylalanine‬
‭testosterone and DHEAS‬ ‭●‬ ‭Present in highest concentration in the regions of the brain‬
‭●‬ ‭In R-zone‬ ‭●‬ ‭Major metabolite:‬‭HVA‬
‭○‬ ‭Main steroid is DHEA and DHEAS (androgen precursor)‬
‭○‬ ‭Main regulator is Not know‬
‭Reproductive Hormones and Other Miscellaneous Hormones‬
‭Reproductive Hormones‬
‭○‬ ‭Testosterone‬
‭○‬ ‭Dehydroepiandrosterone (DHEA)‬
‭○‬ ‭Estrogen‬
‭○‬ ‭Progesterone‬
‭Other Hormones‬
‭●‬ ‭Pancreas‬
‭○‬ ‭Glucagon, Insulin, Somatostatin‬
‭Other Miscellaneous Hormones‬
‭○‬ ‭Human Chorionic Gonadotropin‬
‭○‬ ‭Human Placental Lactogen‬
‭○‬ ‭Gastrin‬
‭○‬ ‭Serotonin‬
‭○‬ ‭Inhibin A‬
‭Reproductive Hormones‬

‭Testosterone‬
‭‬ P
● ‭ rincipal‬‭androgen hormone‬‭- most potent‬
‭●‬ ‭Synthesized by the Leydig Cells of the testis of the male, derived from‬
‭Progesterone‬
‭●‬ ‭Controlled by‬‭FSH and LH‬
‭Clinical Disorders and Methods‬
‭●‬ ‭Function:‬‭growth and development of the reproductive system, prostate and‬
‭●‬ ‭Clinical Disorders‬ ‭external genitalia‬
‭○‬ ‭Pheochromocytoma‬ ‭●‬ ‭Levels demonstrate a circardian pattern and peak at (‬‭8 am‬‭) and fall to their‬
‭○‬ ‭Neuroblastoma‬ ‭lowest level at‬‭8 pm‬
‭●‬ ‭Methods‬ ‭●‬ ‭There is gradual reduction of testosterone after age‬‭30‬‭, with an average decline‬
‭○‬ ‭Chromatography‬ ‭of about 110 ng/dL every decade‬
‭○‬ ‭Radioimmunoassays‬ ‭●‬ ‭Test for male infertility:‬
‭Pheochromocytoma‬ ‭○‬ ‭Semen analysis, testosterone, FSH and LH‬
‭●‬ ‭Tumors of the adrenal medulla or sympathetic ganglia‬ ‭●‬ ‭Reference Values: 3.9 – 7.9 ng/mL (serum)‬
‭●‬ ‭Commonly seen in 3rd to 5th decades of life (30-50s)‬ ‭●‬ ‭Transport proteins‬
‭●‬ ‭Due to‬‭overproduction‬‭of the catecholamine‬ ‭○‬ ‭Sex hormone binding globulin (SHBG)- 60%‬
‭Signs and symptoms:‬ ‭○‬ ‭Albumin- 40%‬
‭●‬ ‭Tachycardia, headache, tightness of chest, sweating, hypertension‬ ‭○‬ ‭Concentration determines the level of testosterone‬
‭Screening Test:‬ ‭Types of Testicular Infertility‬
‭●‬ ‭High plasma metanephrines and normetanephrines by HPLC ((plasma-EDTA)‬ ‭●‬ ‭Pretesticular Infertility (‬‭secondary hypogonadism‬‭)‬
‭Diagnostic Test‬ ‭○‬ ‭Due to‬‭hypothalamic/pituitary‬‭lesions‬
‭●‬ ‭High 24 hour urinary excretion of metanephrines and normetanephrines (urine)‬ ‭○‬ ‭Testosterone, FSH, LH –‬‭Normal/decreased‬
‭Pharmacological test‬ ‭●‬ ‭Testicular Infertility (‬‭primary hypogonadism‬‭)‬
‭1.‬ ‭Clonidine:‬ ‭○‬ ‭May be congenital (cryptorchidism, Klinefelter’s syndrome and 5-a-reductase‬
‭○‬ ‭Differentiates pheochromocytoma (not suppressed) to neurogenic‬ ‭deficiency) or acquired (varicocele, tumor, orchitis)‬
‭hypertension (50% decreased cathecolamines)‬ ‭○‬ ‭Decreased‬‭testosterone levels and‬‭Increase‬‭FSH and LH‬
‭○‬ ‭Confirmatory: 0.3 mg clonidine → patient → differentiate the borderline‬ ‭●‬ ‭Post-testicular infertility‬
‭result from 1,000-2,000 pg/mL‬ ‭○‬ ‭Due to disorders of sperm‬‭transport and function‬
‭2.‬ ‭Glucagon Stimulation Test‬ ‭○‬ ‭Testosterone, FSH, and LH-‬‭Normal‬
‭○‬ ‭Used if it is highly suggestive of pheochromocytoma but blood pressure is‬
‭Other Disorders of Sexual Development‬
‭normal and cathecolamines are modestly elevated: 3 folds increased‬
‭1.‬ ‭Testicular feminization Syndrome‬
‭Neuroblastoma‬
‭○‬ ‭Most severe form of androgen‬‭resistance syndrome, resulting in‬‭Lack‬‭of‬
‭●‬ ‭A fatal malignant condition in‬‭children‬‭resulting to‬‭excessive production of‬ ‭testosterone action in the target tissue‬
‭norepinephrine‬ ‭○‬ ‭Physical development pursues the female phenotype, with fully developed‬
‭●‬ ‭(+) high urinary excretion of (HVA) or VMA or both and dopamine‬ ‭breast and female distribution of fat and hair‬
‭●‬ ‭Specimen:‬‭24 hour urine and blood (plasma)‬ ‭○‬ ‭No‬‭utility or response to administration of exogenous testosterone‬
‭Patient Preparation‬ ‭○‬ ‭Lab tests:‬‭Normal‬‭levels of testosterone with‬‭elevated‬‭FSH and LH‬
‭●‬ ‭The patient should undergo‬‭overnight fasting‬ ‭2.‬ ‭Sertoli-cell only syndrome‬
‭●‬ ‭Avoid smoking or drinking coffee at least‬‭4 hours‬‭prior to blood collection‬ ‭○‬ ‭Characterized by lack of‬‭germ cells‬
‭●‬ ‭The patient is placed in a reclining position in quiet environment and a heparin‬ ‭○‬ ‭Men present with small testes, high FSH levels, azoospermia, and normal‬
‭lock is inserted intravenously.‬ ‭testosterone level‬
‭●‬ ‭After‬‭20 to 30 mins‬‭blood is collected in a‬‭pre-chilled EDTA tube‬ ‭○‬ ‭Testicular biopsy‬‭is the only procedure to confirm this diagnosis‬
‭●‬ ‭Plasma concentrations of cathecolamines are affected by body positioning‬ ‭3.‬ ‭Kallman’s syndrome‬
‭and samples must be collected after 30 mins in a stable position decreased‬ ‭○‬ ‭A result of an inherited, X-linked recessive trait that manifests as‬
‭value when supine‬ ‭hypogonadism during puberty‬
‭○‬ ‭Reclining position‬ ‭Dehydroepiandrosterone‬
‭Methods‬ ‭●‬ ‭The principal androgen formed by the adrenal cortex; weak androgen‬
‭●‬ ‭Chromatography‬ ‭●‬ ‭Derived from the adrenal gland‬
‭○‬ ‭HPLC or GC-MS – (VMA and metanephrines)‬ ‭●‬ ‭Valuable in the assessment of adrenal cortical hormones‬
‭●‬ ‭Radioimmunoassay‬ ‭Estrogen‬
‭○‬ ‭Sensitive screening test for total plasma cathecolamines‬ ‭●‬ ‭Arises through structural alteration of the‬‭testosterone‬‭molecule‬
‭○‬ ‭> 2000pg/mL of plasma cathecolamines- diagnostic for pheochromocytoma‬ ‭●‬ ‭Function:‬‭promotion of breast development, maturation of external genitalia,‬
‭Specimen Consideration‬ ‭deposition of body fat (secondary sexual characteristic of female)‬
‭●‬ ‭Catheterization:‬ ‭●‬ ‭In conjunction with‬‭progesterone‬‭, they function in uterine growth and regulation‬
‭○‬ ‭Preferred method of blood collection to eliminate anxiety of venipuncture‬ ‭of menstrual cycle and maintenance of pregnancy‬
‭●‬ ‭Urine Preservation‬ ‭●‬ ‭Deficiency:‬‭irregular and incomplete development of‬‭the endometrium‬
‭○‬ ‭Urine samples with‬‭10 mL of 6N HCl‬‭(cathecolamines and metabolitesare‬ ‭●‬ ‭Precursor:‬‭acetate, cholesterol, progesterone and‬‭testosterone‬
‭rapidly oxidized at higher pH‬ ‭●‬ ‭Forms:‬‭estrone, estradiol and estriol‬
‭●‬ ‭24-hour urine creatinine test‬ ‭●‬ ‭Estrone and estriol are metabolites of intraovarian and extraglandular conversion‬
‭○‬ ‭To assess the quality of urine collection (0.8 g/day of urine creatinine is‬ ‭A.‬‭Estrone‬
‭needed to validate the‬‭completeness of the urine‬‭collection)‬ ‭●‬ ‭The most‬‭abundant‬‭estrogen in postmenopausal women‬
‭●‬ ‭To prevent‬‭catecholamine oxidation‬‭,‬‭blood samples must be transported on‬
‭B.‬‭Estradiol‬
‭ice‬
‭●‬ ‭Most‬‭potent‬‭estrogen secreted by the ovary, major estrogen‬
‭●‬ S ‭ ynthesized from‬‭testosterone‬‭, then diffuses out of the thecal cells of the‬ ‭Serotonin (5 hydroxytryptamine)‬
‭ovaries of the female‬ ‭‬
● ‭ n amine derived from hydroxylation and decarboxylation of tryptophan‬
A
‭●‬ ‭Precursor‬‭of both E1 and E3 – serves as negative feedback for‬‭FSH‬ ‭●‬ ‭Synthesized by‬‭argentaffin cells‬‭, primarily in GI tract‬
‭●‬ ‭Used to assess‬‭Ovarian Function‬ ‭●‬ ‭Also found in high concentration in pineal gland and CNS‬
‭●‬ ‭Transport proteins: Albumin (60%) and SHBG (38%)‬ ‭●‬ ‭Binds to platelets and released during coagulation‬
‭●‬ ‭Free form of E2 is approximately 2%‬ ‭●‬ ‭Urinary metabolites:‬‭5-HIAA‬
‭C.‬‭Estriol - metabolite of estradiol‬ ‭●‬ ‭5-HIAA‬‭is a diagnostic marker for‬‭carcinoid tumor‬
‭●‬ ‭Estrogen found in the‬‭maternal urine‬ ‭●‬ ‭Test for 5-HIAA:‬‭Ehrlich’s Aldehyde‬
‭●‬ ‭Major estrogen secreted by the placenta during pregnancy- formation in the‬ ‭Somatostatin‬
‭pregnant women is dependent on fetal and placental function‬ ‭‬
● ‭Also called‬‭Growth Inhibiting Hormone‬
‭●‬ ‭Used to assess the fetoplacental unit (‬‭fetoplacental viability‬‭), postdate‬ ‭●‬ ‭Found in the GIT, hypothalamus and delta cells of the pancreas‬
‭gestations and intrauterine retardation‬ ‭●‬ ‭An inhibitor of‬‭GH, Glucagon and insulin‬
‭●‬ ‭Used as marker for Down Syndrome‬ ‭Inhibin A‬
‭●‬ ‭Preferred specimen:‬‭Plasma‬ ‭●‬ ‭a reproductive system hormone which inhibits‬‭FSH activity‬
‭Progesterone‬ ‭Methods‬
‭●‬ ‭Produced by the granulose (lutein) cells of the corpus luteum in the female‬
‭●‬ ‭Prime‬‭secretory product‬‭of the ovary‬
‭Sample for Hormonal Assay‬
‭●‬ ‭Dominant hormone responsible for the luteal phase cycle among females‬
‭1.‬ ‭Whole blood‬‭: LH and Testosterone‬
‭●‬ ‭Single best hormone to determine whether‬‭ovulation‬‭has occured‬
‭2.‬ ‭Plasma‬
‭●‬ ‭Primarily for the evaluation of‬‭fertility‬‭in female‬
‭○‬ ‭EDTA‬‭(ACTH, ADH, PTH)‬
‭●‬ ‭Serves to prepare the uterus for pregnancy and the lobules of the breast for‬
‭○‬ ‭Heparin‬‭(Cathecolamines, Cortisol, Dopamine, FSH)‬
‭lactation‬
‭3.‬ ‭Serum‬
‭●‬ ‭Deficiency: failure of implantation of the embryo‬
‭○‬ ‭Aldosterone, androstenedione, DHEA, estrogen, FSH, GH, HCG,‬
‭●‬ ‭Metabolites: pregnanediols, pregnanediones, pregnanelones‬
‭progesterone0‬
‭4.‬ ‭Urine‬‭: Estriol‬
‭Test for Menstrual Cycle Dysfunction‬ ‭Test for female‬‭Infertility‬
‭○‬ ‭Boric Acid‬‭(1 g/dL) preserves estriol and estrogen for 7 days‬
‭and Anovulation‬
‭○‬ ‭10 mL of 6N HCl‬‭is added to 3-4 L of container (cathecolamines,‬
‭Estrogen‬ ‭ CG‬
H
‭Progesterone‬ ‭PRL‬ ‭vanillylmandelic acid, 5-HIAA)‬
‭FSH‬ ‭FT4‬ ‭Classic Assays‬
‭LH‬ ‭TSH‬ ‭●‬ ‭Bioassays‬
‭FSH‬ ‭●‬ ‭Competitive Protein Binding‬
‭LH‬ ‭Immunologic Assays‬
‭Estradiol‬ ‭●‬ ‭Radioimmunoassays‬
‭Progesterone‬ ‭●‬ ‭Immunoradiometric Assays‬
‭●‬ ‭Enzyme-linked Immunosorbent Assays‬
‭Pancreas‬ ‭●‬ ‭Enzyme Multiplied Immunosorbent Technique‬
‭ ‬ ‭A digestive gland in the‬‭gastrointestinal system‬
● ‭Fluorescent Techniques‬
‭Functions‬ ‭●‬ ‭Fluorescence Polarization Immunoassay‬
‭1.‬ ‭Exocrine:‬
‭High Performance Liquid Chromatography‬
‭●‬ ‭Responsible for the synthesis of digestive enzymes‬
‭●‬
‭●‬ ‭Acinus: functional secretory unit‬
‭Colorimetry‬
‭2.‬ ‭Endocrine‬
‭●‬ ‭Responsible for the synthesis‬ ‭●‬
‭●‬ ‭Alpha cells (20-30%) –‬‭glucagon‬ ‭Classic Assays‬
‭●‬ ‭Beta cells (60-70%) –‬ ‭insulin‬ ‭Bioassay‬
‭●‬ ‭Delta cells (2-8%) -‬‭somatostatin‬ ‭●‬ ‭Based on observation of physiologic responses specific for the hormone being‬
‭Human Chorionic Gonadotropin (HCG)‬ ‭measures‬
‭●‬ ‭Produced by the trophoblast cells of the placenta‬ ‭●‬ ‭Involves‬‭injection‬‭of the test materials into animals‬
‭●‬ ‭Serves to maintain‬‭progesterone production‬ ‭by the corpus luteum in the early‬ ‭Competitive Binding Protein‬
‭pregnancy‬ ‭●‬ ‭Based on competition for protein-binding sites between a known‬‭“tagged/label”‬
‭●‬ ‭Can be detected‬‭2-3 days‬‭after ovulation‬ ‭hormone and the unlabeled hormone in the patient’s sample‬
‭●‬ ‭Qualitative test for urine samples has detection limit of about 50 mIU/mL‬ ‭●‬ ‭Measurement of total T4 is based on the specific binding properties of TBG‬
‭●‬ ‭Method: Immunometric (sandwich) method‬ ‭Immunologic Assays‬
‭Human Placental Lactogen‬ ‭●‬ ‭widely used to quantify hormones using labeled-antibody with‬‭non-isotopic‬
‭●‬ ‭Functionally, structurally and immunologically similar to‬‭Growth Hormone and‬ ‭labels‬
‭Prolactin‬ ‭Radioimmunoassays‬
‭●‬ ‭Can be measured in‬‭Urine, serum, and amniotic fluid‬ ‭●‬ ‭Is a CBP technique that utilizes‬‭radio labeled‬‭hormone as the tagged hormone‬
‭●‬ ‭Stimulates the development of the‬‭mammary gland‬ ‭and antisera prepared against the specific hormone as the binding site‬
‭●‬ ‭Increases maternal plasma glucose level and promotes positive nitrogen balance‬ ‭Immunoradiometric Assay‬
‭●‬ ‭Important in the diagnosis of intrauterine growth retardation‬ ‭●‬ ‭A radiolabeled substance is attached to the antibody instead of the hormone; an‬
‭Gastrin‬ ‭antigen-antibody reaction‬
‭●‬ ‭A peptide secreted by the G cells of the antrum of the stomach‬ ‭ELISA‬
‭●‬ ‭Released in response to‬‭vagal‬‭stimulation and‬‭Food‬‭in the stomach‬ ‭●‬ ‭An‬‭enzyme‬‭attached to an antibody in which the end product can be measured‬
‭●‬ ‭Causes secretion of the‬‭HCl‬‭by parietal cells‬ ‭spectrophotometrically‬
‭●‬ ‭Diagnostic marker for‬‭Zollinger-Ellison syndrome‬ ‭Enzyme Multiplied Immunosorbent Technique (EMIT)‬
‭●‬ ‭Major stimulus: presence of‬‭Amino Acid‬ ‭●‬ ‭Enzyme tags are used; the enzyme is attached to the hormone or drug being‬
‭●‬ ‭Increased levels‬‭: ZES, Achlorhydria, Chronic Renal‬‭Failure‬ ‭tested‬
‭Gastric Fluid Acidity‬ ‭●‬ ‭The rate of‬‭NADH‬‭produced is proportional to the amount of drug tested‬
‭●‬ ‭G cells → secrete gastrin‬ ‭●‬ ‭Requires of‬‭no separation‬‭bound and free antigen This method is widely used in‬
‭●‬ ‭Parietal cells (Gastrin) → HCl‬ ‭TDM‬
‭●‬ ‭Chief cells (produce pepsinogen) → HCl → pepsin‬ ‭Immunometric‬
‭BAO‬ ‭BAO/MAO‬ ‭●‬ ‭For‬‭TSH‬‭test; sensitive test‬
‭Basal Acid Output‬ ‭Maximal Acid Output‬
‭Fluorescent Techniques‬
‭NORMAL‬ ‭2.5‬ ‭10%‬
‭PERNICIOUS ANEMIA‬ ‭0‬ ‭0‬ ‭Fluorescence Polarization Immunoassay‬
‭GASTRIC CARCINOMA‬ ‭1.0‬ ‭25%‬ ‭●‬ ‭flourescein-labeled drug, serum, and antibody are mixed and placed in the light‬
‭DUODENAL CANCER‬ ‭5.0‬ ‭17%‬ ‭path of a fluorometer.‬‭Antibody bound conjugate is inversely proportional to‬
‭ZOLLINGER-ELLISON SYNDROME‬ ‭18.0‬ ‭72%‬ ‭serum drug concentration‬
‭High Performance Liquid Chromatography‬
‭●‬ ‭Based on the differential‬‭partitioning‬‭of the compounds between the mobile‬
‭phase and stationary phase‬
‭Colorimetry‬
‭A.‬‭Porter-silber method:‬‭17-OCHS‬
‭B.‬‭Zimmermann Reaction‬
‭○‬ ‭measures those steroids with 17-KS‬
‭C.‬‭Pisano Method‬
‭○‬ ‭For quantifying metanephrines and normetanephrines‬
‭D.‬ ‭Kober Reaction‬
‭○‬ ‭For estrogen‬
‭○‬ ‭H2SO4 + hydroquinone‬
‭○‬ ‭(+) reddish brown color‬
‭Summary Of Glands And Hormones‬

‭Gland‬ ‭Hormones‬
‭ nterior Pituitary Gland‬
A ‭ H, TSH, ACTH, MSH, LH/ICSH, FSH, PRL‬
G
‭Posterior Pituitary Gland‬ ‭ADH, Oxytocin‬
‭Thyroid Gland‬ ‭T3, T4, Calcitonin‬
‭Parathyroid Gland‬ ‭PTH‬
‭Adrenal Gland‬ ‭Epinephrine, norepinephrine, dopamine,‬
‭mineralocorticoids, glucocorticoids, adrenal‬
‭androgens‬
‭ ancreas‬
P ‭Insulin, glucagon, somatostatin‬
‭Reproductive Gland‬ ‭Testosterone, estrogens, progesterone‬
‭Thymus Gland‬ ‭Thymosin‬
‭Pineal Gland‬ ‭Melatonin‬

You might also like