Thyroid and Sex Hormone Editable Notes PDF

THYROID GLAND It is also known as the _________________ It is consist of two lobes (one on either side of the trachea) located in the lower part of the neck, just below the voice box (larynx). The lobes are connected by a narrow band called the isthmus. By ______________________, the gland begins to...

THYROID GLAND It is also known as the _________________ It is consist of two lobes (one on either side of the trachea) located in the lower part of the neck, just below the voice box (larynx). The lobes are connected by a narrow band called the isthmus. By ______________________, the gland begins to produce measurable amounts of hormone. _________________ the fundamental structural unit of the thyroid gland. 2 types of cells: follicular cells (T3 and T4) parafollicular or C cells (Calcitonin) ____________ is a glycoprotein; it acts as a preformed matrix containing tyrosyl groups; it is stored in the follicular colloid of the thyroid gland. Biosynthesis of Thyroid Hormones ____________ is the most important element in the biosynthesis of thyroid hormones. Iodination of tyrosine residues in thyroglobulin results in formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT). TSH stimulates synthesis of thyroid hormones. * Protein bound hormones are metabolically inactive - free hormones (FT3 and FT4) are the physiologically active portions of the thyroid hormones. * Protein-bound thyroid hormones do not enter cells and are considered to be biologically inert and function as storage sites for circulating thyroid hormones. The minute levels of free hormone fractions readily enter cells by specific membrane transport mechanism to exert their biological effects; the effects are mediated by T3 receptors located in the nucleus of the cell. When iodide sources are diminished, MIT is produced in greater quantities, leading to __________ T3 formation and release. Reverse T3 is produced by removal of one iodine from the inner ring of T4; __________________, product of T4 metabolism. The hypothalamic-pituitary-thyroid axis (HPTA) is the neuroendocrine system that regulates the production and secretion of thyroid hormones. Iodine intake below 50pg/day is an indication of the deficiency of hormone secretion. Thyroid hormones affect synthesis, degradation, and intermediate metabolism of adipose tissue and circulating lipids. Functions of Thyroid Hormones: 1. For tissue growth. 2. For mental development. 3. For development of the central nervous system. 4. Elevated heat production. 5. Control of oxygen consumption. 6. It influence carbohydrate and protein metabolism. 7. For energy conservation. Major Thyroid Hormones: 1. Triiodothyronine (Ta)/ 3,5,3’ triiodothyronine. It has the most active thyroid hormonal activity. * Almost 75-80% is produced from the tissue deiodination of T4- conversion of T4 to T3 takes place in many tissues, particularly the ________________________. The principal application of this hormone is in diagnosing T3 thyrotoxicosis. It is a better indicator of recovery from hyperthyroidism as well as the recognition of recurrence of hyperthyroidism - it is helpful in confirming the diagnosis of hyperthyroidism, especially in patients with no or minimally elevated T4. An increase in the plasma level of T3 is the first abnormality seen in cases of _________________. Reference value: Adult- 60-160 pg/dL or 0.9-2.46 nmol/L Children 1-14 years old - 105-245 ng/dL or 1.8-3.8 nmol/L 2. Tetraiodothyronine (T4)/3,5,3’’* tetraiodothyronine It is the principal ____________ product. It has the major fraction of organic iodine in the circulation. It is a prohormone for T3 production. All circulating T4 originates in the thyroid gland - it is secreted 100% in the thyroid gland. The amount of serum T4 is a good indicator of the ________________________ Elevated _______________ causes inhibition of TSH secretion, and vice versa. * Reference value: 5.5-12.5pg/dL or 71-161 nmol/L (adult) 11.8- 22.6 pg/dL or 152-292 nmol/L (neonate) Thyroid Hormone Binding Proteins: 1. Thyroxine-Binding Globulin (TBG) it transports majority of T4 (affinity for T3 is lower than T4). it transports 70-75% of total T4. 2. Thyroxine-Binding Prealbumin (transthyretin) it transports 15-20% of total T4. T3 has no affinity for prealbumin. 3. Thyroxine-Binding Albumin it transports T3 and 10% of T4. Clinical Disorders; Screening of thyroid disorders is recommended when a person reaches ______________________ 1. Hyperthyroidism " It refers to an excess of circulating thyroid hormone. » Signs and symptoms: tachycardia, tremors, weight loss, heat intolerance, emotional lability and menstrual changes Primary hyperthyroidism ~ elevated T3 and T4, decreased TSH Secondary hyperthyroidism - increased FT4 and TSH a. Thyrotoxicosis is applied to a group of syndromes caused by high levels of Free thyroid hormones in the circulation. T3 thyrotoxicosis or Plummer's disease: FT3 increased but FT4 normal with low TSH T4 thyrotoxicosis: T3 normal or low but T4 increased with low TSH b. Graves’ disease It is the most common cause of _______________ It is an autoimmune disease in which antibodies are produced that activate the TSH receptor. It occurs 6x more commonly in women than in men. Features: exophthalmos and pritibial myxedema Diagnostic test: TSH receptor antibody test c. Riedel's thyroiditis » The thyroid turns into a woody or stony-hard mass. d. Subclinical hyperthyroidism >> shows no clinical symptoms but TSH level is low, and FT3 and FT4 normal. e. Subacute granulomatous/Subacute nonsuppurative thyroiditis/De Quervain thyroiditis it is associated with neck pain, low-grade fever and swings in thyroid function tests. the thyroidal peroxidase (TPO) antibodies are absent; ESR and thyroglobulin levels are elevated. 2. Hypothyroidism It develops whenever insufficient amounts of thyroid hormone are available to tissues. It is treated with thyroid hormone replacement therapy signs and symptoms: bradycardia, weight gain, coarsened skin, cold intolerance and mental dullness a. Primary hypothyroidism it is primarily due to deficiency of elemental iodine it is also caused by destruction or ablation of the thyroid gland. Other causes: surgical removal of the gland; used of radioactive iodine for hyperthyroidism treatment; radiation exposure; drugs such as lithium Hashimoto’s disease is the most common cause of ____________ hypothyroidism. it is characterized by a thyroid replaced by a nest of lymphoid tissue - sensitized T lymphocytes/autoantibodies bind to cell membrane causing cell lysis and inflammatory reaction. it is associated with enlargement of the thyroid gland lab result: high TSH and positive TPO antibody Myxedema it describes the peculiar nonpitting swelling of the skin. the skin becomes infiltrated by mucopolysaccharides. clinical features: "puffy" face, weight gain, slow speech, eyebrows thinned, dry and yellow skin, and anemia myxedema coma is the severe form of primary hypothyroidism b. Secondary hypothyroidism it is due to pituitary destruction or pituitary adenoma. lab result: T3 and T4 low levels, TSH is also decreased. c. Tertiary hypothyroidism it is due to hypothalamic disease. lab result: T3 and T4 low levels, TSH is also decreased. d. Congenital hypothyroidism it is a defect in the development or function of the gland. r symptoms: physical and mental development of the child are retarded screening test: T4 (decreased) confirmatory test: TSH (increased) interpretation: TSH value 20 mIU/L - for endocrinologic evaluation to diagnose hypothyroidism e. Subclinical hypothyroidism lab result: T3 and T4 normal but TSH is slightly increased Thyroid Function Tests: 1. TRH Stimulation Test (Thyrotropin Releasing Hormone) it measures the relationship between the TRH arid TSH secretions it is used to differentiate euthyroid and hyperthyroid patients who both had undetectable TSH levels. it may also be helpful in the detection of thyroid hormone resistance syndromes. it is used to confirm borderline cases and euthyroid Grave's disease. dose needed: 500 pg TRH by IV increased: primary hypothyroidism decreased: hyperthyroidism 2. TSH Test it is the ___________________________ - the best method for detecting clinically significant thyroid dysfunction. it is the most clinically sensitive assay for the detection of ______________ thyroid disorders. it helps in the early detection of hypothyroidism. it is used to differentiate primary hypothyroidism from secondary hypothyroidism. it is used to monitor and adjust thyroid hormone replacement therapy. the sensitivity of the third-generation TSH assays has led to the ability to detect what is termed subclinical disease—or a mild degree of thyroid dysfunction (due to the large reciprocal change in TSH levels seen for even small changes in free T4). reference values: 0.5-5 pU/mL Increased TSH Decreased TSH 1. Primary hypothyroidism 1. Primary hyperthyroidism 2. Hashimoto's thyroiditis 2. Secondary and Tertiary hypothyroidism 3. Thyrotoxicosis due to pituitary tumor 3. Treated Grave's disease 4. TSH antibodies 4. Euthyroid sick disease 5. Thyroid hormone resistance 5. Over replacement of thyroid hormone in hypothyroidism 3. Radioactive Iodine Uptake (RAJU) it is used to measure the ability of the thyroid gland to trap iodine. it is helpful in establishing the cause of hyperthyroidism. high uptake indicates metabolically active gland high uptake + TSH deficiency = autonomous thyroid activity 4. Thyroglobulin (Tg) assay it is normally used as a ____________________ of thyroid cancer. it is used in monitoring the course of metastatic or recurrence of thyroid cancer (a well- differentiated tumors typically display a 10-fold increase in Tg in response to a high TSH). when measuring thyroglobulin as a tumor marker for thyroid cancer, always check a simultaneous sample for thyroglobulin antibodies. it differentiates subacute thyroiditis from thyrotoxicosis factitial increased: untreated and metastatic differentiated thyroid cancer, nodular goiter and hyperthyroidism decreased: infants with goitorous hypothyroidism and thyrotoxicoxis factitia reference value: Adult- 3-42 ng/mLorpg/mL Infant = 38-48 ng/mL or pg/mL ( methods for testing: double-antibody RIA, ELISA, immunochemiluminescent assay (ICMA) 5. Reverse T3 (rT3) it is formed by the removal of one iodine from the inner ring of T4. it is an _______________ of T4 metabolism; the _________ major circulating thyroid hormone. it identifies patients with euthyroid sick syndrome (elevated rT3). it is used to assessed borderline or conflicting laboratory results.  reference value: 38-44 ng/dL 6. Free Thyroxine Index (FTl or T7) it indirectly assesses the level of ____________ in blood. it is based on the equilibrium relationship of bound T4 and FT4. it Is important in correcting euthyroid individuals. it is elevated in hyperthyroidism and decreased in hypothyroidism. reference value: 5.4-9.7 FTI = TT4 x T3U (%) or TT4 X THBR 100 7. Total T3 (TT3), Free T3 (FT3) and FreeT4 (FT4) FT4 test is used to differentiate drug induced TSH elevation and hypothyroidism. the value of TT3 or FT3 is in confirming hyperthyroidism. ’ direct/reference method: Equilibrium dialysis (FT4) 8. T3 Uptake it measures the number of available binding sites of the thyroxine-binding proteins, most notably TBG, a test for TBG. it does not measure the level of T3 in serum but it reflects the serum level of TBG. is inversely related to TBG - decreasedT3 uptake results to elevated TBG result, and vice versa. Increased: hyperthyroidism, euthyroid patients, chronic liver disease decreased: hypothyroidism, oral contraceptives, pregnancy, acute hepatitis reference value: 25-35% 9. Thyroxine binding globulin (TBG) it is used to confirm results of rT3 and FT4, or. abnormalities in the relationship of the total thyroxine (TT4) and THBR test. it is useful in distinguishing between hyperthyroidism) and euthyroidism it helps in the diagnosis of patients having elevated T3 and T4 levels but no correlation with the other thyroid function tests, or not compatible with clinical findings. TBG excess leads to increased serum levels T3 and T4, but the unbound or free form of these hormones in the blood remain unchanged. hormonal effect: _____________ increases TBG while _______________ depress TBG increased: euthyroidism, pregnancy and estrogen surge decreased: anabolic steroids and nephrosis reference value: 13-39 |ig/dL (150-360 nmol/L) 10. Fine-needle aspiration- is the most accurate tool in the evaluation of thyroid nodules 11. Recombinant Human TSH it is used to test patients with thyroid cancers for the presence of residual or recurrent disease. 12. Tanned Erythrocyte Hemagglutination it is a measure of antithyroglobulin antibodies. 13. Serum Calcitonin it is a tumor marker for detecting residual thyroid metastasis in medullary thyroid carcinoma (MTC] it should be measured before and ______________ after surgery. 14. Pentagastrin (Pg) Stimulation Test it is used for the diagnosis of MTC. procedure: an intravenous Pg (0.5 pig/kg body weight) is given within _______; blood samples are collected at baseline-and 1,2,5, and 10 minutes after the start of the infusion Notes to Remember. > Abnormal values of total T3 or T4 must be evaluated with TBG measurement. > Free T4 and TSH are the best indicators of ________________ > Free T3 and T4 are more specific indicators of thyroid function than the measurements of total hormone because the values are not affected by the TBG amount. > Patients with increased T4-binding protein have an elevated T3 or T4 but not free T4 or TSH. > Euthyroid sick syndrome is acutely ill but without thyroid disease - low T3 and T4, and normal or increased TSH, but elevated rT3. > Euthyroid with elevated T4-binding protein is due to increase in ____________. > Patients with nonthyroidal illness (NTI) have low or low-normal TSH and normal or low-normal T4 but very low T3 during their acute illness. > ln severe hypothyroidism, _________________ values rise moderately. >Calcitonin is measured by two-site immunometric assays using __________________, and it is also elevated in autoimmune thyroid disorder, hypercalcemia and all neuroendocrine tumors. > Cutoff value for calcitonin is 10ng/L (adults). REPRODUCTIVE HORMONES Synthesis and Transport of Hormones: The testes and ovaries produce sex steroids such as androgens and estrogens from __________ The ovary converts testosterone to estradiol, and androstenedione to estrone. Peripheral tissues reduce testosterone to dihydrotestosterone (DHT), hydroxylate estradiol to estriol, convert adrenal androgens to testosterone and androgens to estrone and estradiol. Major transport protein: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG) and albumin SHBG transports __________________ CBG delivers _________________________ About 1% to 2% of the sex steroids are free (unbound), the remaining are bound to proteins (Albumin, SHBG and CBG). Only the free fraction of the hormone is biologically active, because only the free form can diffuse into the vascular system and interact with target cells. 1. T estosterone It is the principal androgen hormone in the blood - _____________________ It is synthesized by the Leydig cells of the testis of the male; also derived from progesterone. It is controlled primarily by FSH and LH. Functions: growth and development of the reproductive system, prostate and external genitalia Physiologic factors: o Levels demonstrate a circadian pattern and peak at _______________________ fall to their lowest level at ____________________ o There is a gradual reduction in testosterone after age ___________, with an average decline of about 110 ng/dL every decade. o Obesity may cause decrease plasma testosterone concentration. o After age 50, men experience a decrease in secretion rate and concentration of testosterone, and women have an increase in pituitary gonadotropins, especially follicle- stimulating hormone (Young, 2007 cited by Me Pherson and Pincus, 2017). Tests for male infertility: semen analysis, testosterone, FSH and LH Reference values: 3.9-7.9 rig/mL (serum) » 1. Albumin - 50% 2. Sex hormone bindlng-globulin (SHBG)-45% * The concentration of binding protein determines the level of total testosterone but not the free testosterone levels during laboratory estimation. Types of Testicular Infertility (Hypogonadism): a. Pretesticular infertility (Secondary hypogonadism) It is due to hypothalamic or pituitary lesions. Normal or decreased levels: testosterone, FSH and LH levels b. Testicular infertility (Primary hypogonadism) it may be congenital (cryptorchidism, Klinefelter's syndrome and 5-alpha-reductase deficiency) or acquired (varicocele, tumor, orchitis). It is characterized by having decreased testosterone levels and increased FSH and LH levels. c. post-testicular infertility It is due to disorders of sperm transport and function. Normal blood level: testosterone, FSH and LH levels Other Disorders of Sexual Development: a. Testicular Feminization Syndrome It is the most severe form of androgen resistance syndrome, resulting in lack of testosterone action in the target tissue. The physical development pursues the female phenotype, with fully developed breast and female distribution of fat and hair. There is no utility or response to administration of exogenous testosterone. Lab tests: normal levels of testosterone with elevated FSH and LH levels b. Sertoli Cell-Only Syndrome It is characterized by a lack of germ cells. Men present with small testes, high FSH levels, azoospermia, and normal testosterone levels. Testicular biopsy is the only procedure to confirm this diagnosis. c. Kallmann's Syndrome It is a result of an inherited, X-linked recessive trait that manifests as hypogonadism during puberty, Associated defects: anosmia and midline defects 2. Dehydroepiandrosterone (DHEA) It is the principal androgen formed by adrenal cortex; ___________ This androgen is primarily derived from the adrenal gland. It is valuable in the assessment of adrenal cortical function. 3. Estrogen It is carbon-18 steroid hormones that have a phenol A ring. It arises through structural alteration of the testosterone molecule. It is not produced by the ovaries after menopause. Functions: promotion of breast development, maturation of the external genitalia, deposition of body fat and termination of linear growth (secondary sexual characteristic in the female) In conjunction with progesterone, they function in uterine growth and regulation of menstrual cycle, and maintenance of pregnancy. Deficiency: irregular and incomplete development of the endometrium Precursor: acetate., cholesterol, progesterone and testosterone  3 Forms: estrone, estradiol and estriol Estrone and estriol are metabolites of intraovarian and extra glandular conversion o. Estrone (E1) It is the most abundant estrogen in __________________ women. b. Estradiol (E2) It is the most potent estrogen secreted by the ovary; _____________ It is the most abundant estrogen in ________________ women; low levels in the menopausal stage. " It is synthesized from the testosterone, then diffuses out of the thecal cells of the ovaries in the female. It is the precursor of both E1 and E3; It is used to assess ovarian function; stives as negative feedback for FSH. Transport proteins: albumin (60%) and SHBG (38%) The free form of E2 is approximately 2%. c. Estriol (E3) It is a metabolite of ________________ It is the estrogen found in maternal urine. It is the major estrogen secreted by the ________________ during pregnancy - formation in a pregnant women are dependent on fetal and placental function. It is used to assess the fetoplacental unit postdate gestations and intrauterine retardation. It promotes uteroplacental blood flow as potently as other estrogens. It is used as a marker for Down syndrome Preferred specimen: ______________ 4. Progesterone It is a carbon-21 compound in the steroid family. It is produced mainly by the granulose cells of the corpus luteum in the female. Is the prime secretory product of the ovary. It is a dominant hormone responsible for the luteal phase cycle among females. It is the single best hormone to determine whether _______________ has occurred. It is used primarily for the __________________ in female. * It serves to prepare the uterus for pregnancy and the lobules of the breast for lactation. It is intermediate in the synthesis of adrenal steroids and androstenedione. Deficiency: failure of implantation of embryo Metabolites: pregnanediols, pregnanediones, pregnanalones Tests for menstrual cycle dysfunction and anovulation: estrogen, progesterone, FSH, LH Tests for female infertility: HCG, PRL, FT4, TSH, FSH, LH, estradiol and progesterone Notes to Remember > All estrogens have a hydroxyl group at C3 - E2 has a 2nd hydroxyl group at C17, and E3 has a 3rd hydroxyl group at C16. > Ovaries also produce androgens like androstenedione, dehydroandrostenedione, testosterone and dihydrotestosterone. > Excess production of ovarian androgens among females leads to hirsutism, defeminization or virilization. > SHBG levels are increased with decreased testosterone, increased estrogen, hyperthyroidism, and liver disease, whereas levels are decreased with increased testosterone, hypothyroidism, and acromegaly. > Neural tube defects (NTDs) and Down syndrome (DS) are determined during the early second trimester by screening of maternal serum for levels of AFP, HCG, unconjugated estriol (uE3) and inhibin A. > When one of the four markers of Down's syndrome is abnormal, amniocentesis should be performed. > Karyotyping or FISH typing is a test for Down syndrome using amniotic fluid as specimen.