Endocrinology Lesson 6 Outline PDF

LESSON 6: ENDOCRINOLOGY LESSON 6: ENDOCRINOLOGY OUTLINE ii HYPOPARATHYROIDI...

LESSON 6: ENDOCRINOLOGY LESSON 6: ENDOCRINOLOGY OUTLINE ii HYPOPARATHYROIDISM XXI Endocrine System: V ADRENAL GLAND Z. Hormones: Adrenal Cortex Hormone AA. Feedback Mechanisms: ZZ. Cortisol BB. Types of Hormone Action: Clinical Disorders: XXII Classification of hormones According to Composition or Structure i Hypercortisolism (Cushing Syndrome) H. Peptides and proteins ii Hypocortisolism I. Steroid a) Primary hypocortisolism J. Amines b) Secondary Hypocortisolism XXIII Relational anatomy of pituitary and hypothalamus ACTH stimulation Test: A. Functional Aspects of the a) Insulin Stimulation Test B. Hypothalamic-Hypophysial Unit b) Overnight Metyrapone Test: C. Hypophysiotropic or Hypothalamic Hormones iii Congenital Adrenal Hyperplasia (CAH) ENDOCRINE GLANDS: AAA. Aldosterone (Aldo) I PINEAL GLAND Clinical Disorders II PITUITARY GLANDS (HYPOPHYSIS) i Primary Hyperaldosteronism (Conn’s Disease) CC. Anterior Pituitary (Adenohypophysis) Hormones ii Secondary Hyperaldosteronism i Growth Hormones (GH)/Somatotrophin iii Hypoaldosteronism ii Gonadotropins- Follicle stimulating Hormones (FSH) and BBB. Weak androgens/Adrenal Androgens Leutinizing Hormone (LH) Adrenal Medula Hormone iii Thyroid Stimulating Hormones (TSH) CCC. Norepinephrine (Primary amine) iv Adrenocorticotrophic Hormone (ACTH) DDD. Epinephrine (adrenaline/secondary amine v Prolactin (PRL) EEE. Dopamine (Primary amine) Clinical Disorder Clinical Disorder i Hypopituitarism i Pheochromocytoma DD. Posterior Pituitary (Neurohypophysis) Hormones VI REPRODUCTIVE HORMONES i Oxytocin A. The Testes ii ANTIDIURETIC HORMONES (ADH)/ ARGININE i Testosterone VASOPRESSIN (AVP) VASOPRESSIN ii Dehyroepiandrosterone (DHEA) Clinical Disorder B. The Ovary i Diabetes Insipidus iii Estrogen III THYROID GLAND iv Progesterone A. Triiodothyronine (T3)/(3,5,3’ triiodothyronine) VII PANCREAS B. Tetraiodothyronine (T4) 3,5,3’5’ Tetraiodothyronine Miscellaneous Hormones: C. Thyroid hormone Binding Proteins i Human Chorionic Gonadotropin Clinical Disorder ii Urine Placental Lactogen (HPL) EE. Hyperthyroidism: iii Gastrin i Thyrotoxicosis iv Serotonin (5-hydroxytryptamine) ii Graves’ Disease (diffuse toxic goiter) v Somatostatin: iii Reidel’s Throiditis VIII METHODS iv Subclinical Hyperthyroidism A. Classic Assays v Subacute granulomatous/ Subacute nonsuppurative B. Immunologic Assays thyroiditis/ De Quevain Thyroiditis C. Fluorescent Techniques FF. Hypothyroidism: D. High Performance Liquid Chromatography (HPLC) vi Primary hypothyroidism E. Colorimetry: vii Secondary hypothyroidism: IX Terminologies viii Subclinical hypothyroidism Note for addtl topic heads: GLANDS HORMONES. ix Toxic Adenoma and Multinodular Goiter Note: the FIGURES with broken line border are from synch discussion GG. Drug-Induced Thyroid Dysfunction HH. Nonthyroidal Illness II. Thyroid Nodules INTRODUCTION Thyroid Function Tests: This chapter will discuss the different endocrine JJ. TRH Stimulation Test (Thyrotropin Releasing Hormone) KK. TSH Test gland and their hormones, describe the types of LL. Radioactive Iodine Uptake (RAIU) hormones, and their function. We will discuss the MM. Thyroglobulin (Tg) assay NN. Reverse T3 (rT3) different clinical reference value and their clinical OO. Free Thyroxine (FTI or T7) significance. We will also discuss the different laboratory PP. Total T3 (TT3), Free T3 (FT3) and Free T4 (FT4) QQ. T3 uptake methods used to determine the different hormone in RR. Thyroxine binding globulin their clinical implications. We will discuss the different SS. Fine-needle aspiration TT. Recombinant Human TSH diseases associated with abnormal levels of hormones UU. Tanned Erythrocytes Hemagglutination and how to diagnose them. VV. Serum calcitonin WW. Pentagastrin (Pg) stimulation test ENDOCRINE SYSTEM: IV PARATHYROID GLAND Is a network of ductless glands that secrete hormones directly XX. Parathyroid Hormone YY. Clinical Disorder into the blood i HYPERPARATHYROIDISM It is considered to be the regulatory system of the body EDLET CHRISTINE S. DIONISIO | BSMT 3-3 49  LESSON 7: Therapeutic Drug Monitoring It is regulated by means of control of hormones synthesis 7- NEUROCRINE Is secreted in neurons and rather than by degradation released into extracellular HORMONES: space; binds to receptor in Are chemical signals produced by specialized cells secreted into nearby cell and affects its the blood stream and carried to a target tissue functions They play an important role in the growth and development of 8- NEUROENDOCRINE Is secreted in neurons and an individual released from nerve They are regulated by the metabolic activity either positive and negative feedback mechanisms endings; interacts with Major function: To maintain the constancy of chemical receptors of cells at distant composition of extracellular and intracellular fluids, and control site. metabolism, growth, fertility, and responses to stress FEEDBACK MECHANISMS: CONTROL OF HORMONE SECRETION: a- Positive feedback system: Is a system in which an increased The majority of endocrine functions are regulated through the in the product results to elevation of the activity of the pituitary gland, which in turn is controlled by secretions from the system and the production rate hypothalamus – Example: gonadal, thyroidal and adrenocortical hormones CLASSIFICATION OF HORMONES ACCORDING TO b- Negative feedback system: Is a system in which an increased in the product results to decrease activity of the COMPOSITION OR STRUCTURE: system and the production rate A. PEPTIDES AND PROTEINS – Example: Leutenizing hormone o Are synthesize and stored within the cell in the form of secretory granules and are cleaved as needed o They cannot cross the cell membrane due to their large TYPES OF HORMONE ACTION: molecular size and thus; produce their effects on the outer TYPES DEFINITION surface of the cell 1- ENDOCRINE Is secreted in one location o They are water soluble and not bound to carrier protein and release into blood circulation; binds to specific 1- Glycoprotein: FSH, HCG, TSH, erythropoietin 2- Polypeptides: ACTH, ADH, GH, Angiotensin, calcitonin, receptor to elicit cholecystokinin, gastrin, glucagon, insulin, melanocytes- physiological response stimulating hormones (MSH), oxytoxin, PTH, prolactin, 2- PARACRINE Is secreted in endocrine cells somatostatin and released into interstitial space; binds to specific B. STEROID o Are lipid molecules that have cholesterol as a common receptor in adjacent cell and precursor. affects its function o They are produced by adrenal glands, ovaries, testes and 3- AUTOCRINE Is secreted in endocrine cells placenta and sometimes released o They are water insoluble (hydrophobic) and circulate bound to carrier protein into interstitial space; binds o Examples: aldosterone, cortisol, estradiol, progesterone, to specific receptor on cell of testosterone and activated vitamin D3 origin resulting to self- regulation of its function. C. AMINES 4- JUXTACRINE Is secreted in endocrine cells o They are derived from an amino acid and they are intermediary between steroid and protein hormones remains in relation to o Examples: Epinephrine, norepinephrine, triiothyronine (T3) plasma membrane; acts on and thyroxine immediately adjacent cell by direct cell to cell contact HYPOTHALAMUS: 5- INTRACRINE Is secreted in endocrine cells It is the portion of the brain located in the walls and floor of the and remained as well as third ventricle. It is above the pituitary gland, and is connected to the posterior function inside the synthesis pituitary by the infundibulum (pituitary stalk) of origin It is link between the nervous system and the endocrine system 6- EXOCRINE Is secreted in endocrine cells The supraoptic and paraventricular nuclei produce vasopressin and released into the lumen and oxytocin. of the gut; it affects their ▪ Secretion from hypothalamus, and stored in posterior pituitary gland function. The neurons in the anterior portion release the following hormones (hypophyseal hormones): o thyrotropin-releasing hormone (TRH); EDLET CHRISTINE S. DIONISIO | BSMT 3-3 50  LESSON 7: Therapeutic Drug Monitoring o gonadotropin-releasing hormone (Gn-RH); (Thyroxine) will send signal to hypothalamus to stop o somatostatin also known as growth hormone inhibiting producing TRH. hormone (GH-IH); HYPOPHYSIOTROPIC OR HYPOTHALAMIC HORMONES o growth hormone releasing hormone (GH-RH) Peptides & bioactive amines are most common products of ▪ opposite of somatostatin in function hypothalamus. o prolactin-inhibiting factor (PIF) Hypothalamic hormones often have multiple actions: ▪ TRH stimulates secretion of both TSH & prolactin. RELATIONAL ANATOMY OF PITUITARY AND ▪ GnRH stimulates both LH & FSH production. HYPOTHALAMUS ▪ Somatostatin inhibits GH & TSH release from pituitary. Figure 1. ▪ Vasopressin stimulates water metabolism & ACTH secretion. Hypophysiotropic hormones are found throughout central nervous system, gut, pancreas, & other endocrine glands. Table 1. Hypophysiotropic Hormones HORMONE STRUCTURE ACTION TRH, thyrotropin- 3 amino Releases TSH and releasing acids prolactin hormone GnRH, 10 amino Releases LH and gonadotropin- acids FSH releasing hormone CRH, 41 amino Releases ACTH corticotropin- acids releasing Hypothalamus located in mid-brain; posterior pituitary gland is connected to hypothalamus through infundibulum hormone Secretion from optical nuclei (vasopressin & oxytocin) goes to posterior lobe GHRH, growth 44 amino Releases GH hormone– acids FUNCTIONAL ASPECTS OF THE releasing HYPOTHALAMIC-HYPOPHYSIAL UNIT hormone Afferent pathways (inputs) to hypothalamus are integrated in various specialized nuclei, processed, & resolved into specific Somatostatin 14 and 28 Inhibits GH and patterned responses. amino acids TSH release Characteristics of hypothalamic response patterns (additional effects a) Similar for each specific pituitary hormone on gut and b) Open-loop negative feedback mechanisms (like thermostat) (ex. over-secretion is controlled by pancreatic negative feedback to shut it off) function) c) Pulsatility (secretion may be present/ absent, high/low Dopamine 1 amino Inhibits prolactin at certain condition) (prolactin acid release d) Cyclicity (ex. Diurnal/ circadian) inhibitory factor) SIMPLE FEEDBACK LOOP TSH, thyroid-stimulating hormone; GnRH, Figure 2. gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; ACTH, adrenocorticotropin hormone; ENDOCRINE GLANDS: I. PINEAL GLAND o Is attached to the midbrain o It secretes melatonin that decreases the pigmentation of the skin o Secretion are controlled by nerve stimuli II. PITUITARY GLANDS (HYPOPHYSIS) Ex. Low level of thyroid hormone will send signal to o Is known as the “Master gland” hypothalamus to release thyroid releasing hormone to o It is located in a small cavity in the sphenoid bone of the stimulate pituitary gland to secrete TSH. This will stimulate skull called the sella turcica or Turkish saddle. thyroid gland to release T3 nad T4. Normal levels of T3 and T4 EDLET CHRISTINE S. DIONISIO | BSMT 3-3 51  LESSON 7: Therapeutic Drug Monitoring o It is connected by the infundibular stalk to the median ▪ TSH: directs thyroid hormone production from thyroid eminence of the hypothalamus ▪ ACTH: regulates adrenal steroidogenesis o All pituitary hormones have circadian rhythms Table 2. Anterior Pituitary Hormones PITUITARY o “Master gland”: secretes hormones that regulate other Pituitary Target Structure Feedbac glands Hormone Gland k o Needed for metabolism & gonadal, thyroidal, & adrenal function Hormon o A transponder that translates neural input into a hormonal e or endocrinologic product LH, luteinizing Gonad Dimeric Sex o Distinguishing features of pituitary function hormone; (tropic) glycoprotei steroids a) Feedback loops b) Pulsatile secretions n (E2/T) c) Diurnal rhythms FSH, follicle- Gonad Dimeric Inhibin d) Environmental or external modification of its stimulating (tropic) glycoprotei performance hormone n TSH, thyroid- Thyroid Dimeric Thyroid EMBRYOLOGY AND ANATOMY stimulating (tropic) glycoprotei hormon Three distinct parts of pituitary: hormone n es 1- Anterior pituitary or adenohypophysis (T4/T3) ▪ Largest portion of gland; originates from Rathke’s ACTH, Adrenal Single Cortisol pouch 2- Intermediate lobe or pars intermedialis adrenocorticotro (tropic) peptide ▪ Poorly developed in humans; has little functional pin hormone derived capacity from 3- Posterior pituitary or neurohypophysis POMC ▪ Arises from diencephalon; responsible for storage & Growth hormone Multipl Single IGF-I release of oxytocin & vasopressin ▪ Pituitary resides in a pocket of sphenoid & is e peptide surrounded by dura mater (direct effecto ANTERIOR PITUITARY HORMONES r) Larger & more complex than those from hypothalamus Prolactin Breast Single Unknow Two types (direct peptide n 1. TROPIC: actions are specific for another endocrine gland ▪ GH: affects substrate metabolism & stimulates liver to effecto produce growth factors r) 2. DIRECT EFFECTORS: act directly on peripheral tissue T4, thyroxine; T3, triiodothyronine; E2, estradiol; T, ▪ LH: directs testosterone production from Leydig cells testosterone; POMC, pro-opiomelanocortin; IGF-I, ▪ FSH: ovarian recruitment; folliculogenesis, spermatogenesis insulin-like growth factor. A. ANTERIOR PITUITARY (ADENOHYPOPHYSIS) Is the “True endocrine gland” It regulates the released and production of hormones such as PITUITARY TUMORS prolactin, growth hormone, gonadotropins (FSH and LH), TSH According to autopsy studies, up to 20% of people harbor and ACTH. clinically silent pituitary adenomas. The hormones secreted by this anterior lobe are either peptides Findings consistent with pituitary tumors are observed in 10– or glycoproteins 30% of normal individuals undergoing MRI exams. Pituitary tumors account for 91% of lesions from patients who have undergone transsphenoidal surgery. Physiologic enlargement of pituitary can be seen during puberty 5 types of cells by immunochemical Test: & pregnancy. 1- SOMATOTROPHS- secrete growth hormone 2- LACTOTROPHS OR MAMMOTROPHS- secrete prolactin NOTES TO REMEMBER: 3- THYROTROPHS- secrete TSH The hypothalamus coordinates with the anterior pituitary by 4- GONADOTROPHS- secrete LH, and FSH synthesizing its own trophic hormones that are specific for each 5- CORTICOTROPHS- secretes proopiomelanocortin of the cell population. These trophic hormones pass through the (POMC is cleaved within the pituitary to produce infundibular stalk to the adenohypophysis. ACTH, b- endorphin, and Beta-iipotropin) EDLET CHRISTINE S. DIONISIO | BSMT 3-3 52  LESSON 7: Therapeutic Drug Monitoring α-Agonists (e.g., Thyroxine deficiency HORMONES SECRETED BY THE ANTERIOR PITUITARY GLAND: norepinephrine) A). GROWTH HORMONES (GH)/SOMATOTROPHIN β-Blockers (e.g., o Is the most abundant of all pituitary hormones o Is controlled by the GR-RH (the amount release) and propranolol) somatostatin (governs the frequency and duration of secretory pulse) DISORDERS: o It is structurally similar to prolactin and human placental X GH deficiency (GHD) lactogen o Idiopathic growth hormone deficiency o Its secretion is erratic and occurs in short burst ▪ Is the most common cause of GH deficiency in children o Its overall metabolic effect is to metabolized fat stores while ▪ In children with pituitary dwarfism, normal conserving glucose proportions are retained and show no intellectual o Major stimulus: deep sleep (markedly increased GH) abnormalities o Major inhibitor: Somatostatin o Pituitary adenoma o Physiologic stimuli (increased GH): Stress, fasting and high ▪ Is the most common etiology in adult-onset GH protein diet deficiency o Pharmacologic stimuli (increase GH): sex steroids, apomorphine and levodopa XI Acromegaly o GH suppressors: glucocorticoids and elevated fatty acid o is due to overproduction of GH (>50 ng/mL or 2210 pmol/L) o Increased: Acromegally, chronic malnutrition, renal o Results from pathologic or autonomous growth hormone disease, cirrhosis, and sepsis excess; in most cases, a pituitary tumor o Decrease: hyperglycemia, obesity and hypothyroidism o Causes the following: o Method: chemiluminescent immunoassay ▪ Gigantism o Reference value (fasting): 5 ng/mL (adults) Physiologic stress α-Blockers (e.g., and >10 ng/mL (child) in all the test is confirmed GH deficiency phentolamine) ▪ GHD in childhood is defined by failure of serum GH to Amino acids (e.g., Emotional/psychogenic reach defined levels when at least two different arginine) stress pharmacologic stimuli are used Hypoglycemia Nutritional deficiencies 2- FOR ACROMEGALY Sex steroids (e.g., Insulin deficiency a) Screening Test: Somatomedin C or insulin –like growth estradiol) factor 1 (IGF-1) EDLET CHRISTINE S. DIONISIO | BSMT 3-3 53  LESSON 7: Therapeutic Drug Monitoring ▪ IGF-1 is produced in the liver Specimen for testing should not be allowed to have contact with ▪ IGF-1 is increased in patients with acromegaly glass because ACTH adheres to glass surface resulting to ▪ IGF-1 is low in GHD decrease levels. b) Confirmatory Test: Glucose Suppression Test- OGTT (75g Best time for collecting specimen: 8:00 am to 10:00 am glucose) ▪ Blood is collected every after 30 mins for 2 hours; E) PROLACTIN (PRL) fasting sample is required o Is a pituitary lactogenic hormone; a stress hormone; a direct effector hormone Interpretation of result of acromegaly: o Its amino acid structure is similar to GH o A normal response for this test is a suppression of GH less o Its functions in the initiation and maintenance of lactation than 1 ng/mL o It also acts in conjunction with estrogen and progesterone o If GH fails to decline less than 1 ng/mL, it is acromegaly to promote breast tissue development o Failure of GH to be suppressed below 0.3 ug/, accompanied Major inhibitor: dopamine (secreted by the hypothalamus) by an elevated IGF-1, is diagnostic of acromegaly Consequences of prolactin excess: hypogonadism o Suppression of GH below 0.3 ug/L with normal IGF-1 Increased: pituitary adenoma, infertility, amenorrhea, excludes acromegaly galactorrhea acromegaly, renal failure, polycystic ovary o Suppressions of GH but increase IGF-1, requires follow-up syndrome, cirrhosis and primary and secondary hypothyroidism and monitoring Prolactin serum level>200 mg/dL: pituitary tumor (prolactinoma can result in inovulation) B) GONADOTROPINS- FOLLICLE STIMULATING HORMONES SPECIMEN REQUIREMENT: (FSH) AND LEUTINIZING HORMONE (LH) blood should be collected 3 to 4 hours after the individual has o Is an important marker in diagnosing fertility and menstrual awakened; fasting sample cycle disorders Highest serum level (during sleep): 4:00 am and 8:00 am; o Is present in the blood of both male and female at all ages 8:00pm and 10:00 pm o FSH aids in spermatogenesis (male) METHOD: o LH helps Leydig cells to produce testosterone (male), and for female it is necessary for ovulation and the final o immunometric assay follicular growth PHYSIOLOGIC STIMULI (INCREASED): o LH acts on the thecal cells to cause the synthesis of o exercise, sleep, stress, postprandially, pain, coiyus, androgens, estrogens (estradiol and estrone) and pregnancy, nipple stimulation or nursing progesterone PHARMACOLOGIC (INCREASED): o Elevation of FSH is a clue in the diagnosis of premature o intake of verapamil, phenothiazines, olanzapines, Prozac, menopause cimetidine and opiate o Increase of FSH and LH after menopause is due to lack of REFERENCE VALUE: estrogen o Male: 1-20 ng/mL (1-20 ug/L) C) THYROID STIMULATING HORMONES (TSH) o Female: 1-25 ng/mL (1-25 ug/L) o Is also known as thyrotropin CHARACTERISTICS o It is the main stimulus for the uptake of iodine by the o Structurally related to GH & placental lactogen thyroid gland o Considered a stress hormone; has vital functions in o It acts to increase the number and size of follicular cells; it reproduction stimulates thyroid hormone synthesis o Classified as a direct effector hormone o It is composed of 2 mono-covalently linked to α and ꞵ o Regulates via tonic inhibition, not intermittent stimulation subunits; α subunit has the same amino acid sequences of o Its secretion is inhibited by dopamine. LH, FSH, HCG o Its physiologic effect is lactation. o The ꞵ-subunit carries the specific information to the o Excess prolactin usually leads to hypogonadism. binding receptors for expressions of hormonal activities PROLACTINOMA o Blood levels may contribute in the evaluation of infertility o A pituitary tumor that directly secretes prolactin o Most common type of functional pituitary tumor D) ADRENOCORTICOTROPHIC HORMONE (ACTH) o Clinical presentation depends on patient age/gender, o Is is a single-chain peptide without disulfide bonds tumor size: o It is produced in response to low serum cortisol; regulator ▪ Premenopausal women: menstrual irregularity/ of adrenal androgen synthesis amenorrhea, infertility, galactorrhea o Deficiency of ACTH will lead to atrophy of the zona ▪ Men/postmenopausal women: headaches or visual glomerulosa and zona reticularis (layers of the adrenal complaints cortex) OTHER CAUSES OF HYPERPROLACTINEMIA o Highest level is between 6:00 am to 8:00 am; lowest level o Pituitary stalk interruption, dopaminergic antagonist is between 6:00pm to 11:00 pm. medications, thyroidal failure, renal failure, polycystic ovary o Increased: Addison’s disease, ectopic tumors, after protein- syndrome rich meals CLINICAL EVALUATION OF HYPERPROLACTINEMIA SPECIMEN REQUIREMENT: o Careful history & physical examination Blood should be collected into pre-chilled polysterene (plastic) o Obtain TSH & free T4 levels. (Must be differentiated since EDTA tubes to prevent degradation of ACTH they looked like prolactin) EDLET CHRISTINE S. DIONISIO | BSMT 3-3 54  LESSON 7: Therapeutic Drug Monitoring o If pituitary tumor is suspected, careful assessment of other anterior pituitary function & evaluation of sellar anatomy Table 4. Other Causes of Hypopituitarism w/ MRI (CTScan and MRI) 1. Pituitary tumors 6. Infection MANAGEMENT OF PROLACTINOMA 2. Parapituitary/ 7. Infiltrative disease o Therapeutic goals ▪ Reduce tumor mass hypothalamic tumors ▪ Restore normal gonadal function & fertility 3. Trauma 8. Immunologic ▪ Prevent osteoporosis 4. Radiation 9. Familial ▪ Preserve normal pituitary function therapy/surgery o Therapeutic options: ▪ simple observation, surgery, radiotherapy, medical 5. Infarction 10. Idiopathic management with dopamine (if they don’t want ETIOLOGY OF HYPOPITUITARISM surgery, dopamine will inhibit prolactin) o Pituitary, parasellar, metastatic, & hypothalamic tumors o Postpartum ischemic necrosis of pituitary o Infiltrative diseases: hemochromatosis, sarcoidosis, Idiopathic Galactorrhea histiocytosis o lactation in women with normal prolactin levels o Fungal infections, tuberculosis, syphilis Sone woman produce breast milk even when they are not o Lymphocytic hypophysitis pregnant; but with normal prolactin levels: called idiopathic o Severe head trauma, pituitary surgery, radiotherapy since it is caused by unknown reason TREATMENT OF PANHYPOPITUITARISM o Thyroxine, glucocorticoids, gender-specific sex steroids HYPOPITUITARISM (hormone replacement therapy; pills may be given to Failure of either pituitary or hypothalamus results in loss of woman and testosterone to male) anterior pituitary function: o PANHYPOPITUITARISM: complete loss of function NOTE TO REMEMBER: ▪ All hormone secreted by anterior and posterior It isi essential to obtain TSH and Free T4 (or total thyroxine and pituitary gland are loss T3 resin uptake) to eliminate primary hypothyroidism as a cause o MONOTROPIC HORMONE DEFICIENCY: loss of only a single for the elevated prolactin hormone ▪ Involve only 1 hormone Thyroid hormone replacement therapy will usually return the PRL to normal plasma level Associated with low or normal levels of tropic hormone Three specimens should be obtained at 20-30 minutes intervals Both tropic & target hormone levels should be measured when because of physiologic stimuli- these samples can be measured there is any suspicion of pituitary failure. separately and their results averaged, or, an equal aliquot from If one secondary deficiency is documented, search for other each sample can be pooled into one final sample that is then deficiency states & cause for pituitary failure analyzed. Evaluations in PRL due to physiologic and pharmacologic stimuli Secondary deficiency- may be caused by hypothalamus or rarely exceed 200 ng/mL other organs; not pituitary gland B. POSTERIOR PITUITARY (NEUROHYPOPHYSIS) Is capable of releasing the hormones oxytocin and vasopressin o Synthetic oxytocin, Pitocin, is used in obstetrics to induce but not capable of producing it. labor. The hormones released by neurohypophysis are synthesized in o Has been shown to have effects on pituitary, renal, cardiac, the magnecellar neurons of the supraoptic (ADH) and & immune functions paraventricular nuclei (Oxytocin) of the hypothalamus and Is a nonpeptide, very similar in composition to ADH stored in the nerve terminals that end in the posterior pituitary It is secreted in association with a carrier protein The release of the hormones occurs in response to serum It stimulates contraction of the gravid uterus at term- osmolality or by suckling “Fergusson reflex” (Given when artificial supplements are not Hormones produced by the neurohypophysis are controlled by available) the central nervous system (CNS) ▪ Note: When a female is in labor, and there is decreased oxytocin secretion: the nipples of the mother can be POSTERIOR PITUITARY HORMONES stimulated to release oxytocin and cause uterus Posterior pituitary is an extension of forebrain & represents extraction storage region for oxytocin & vasopressin. ▪ Ex. When the baby is already delivered, but the placenta is not yet out, the baby will be placed closed A). OXYTOCIN: to the breast of the mother. The sucking reflex of the o A cyclic nonapeptide, with a disulfide bridge connecting baby will stimulate the uterus to contact. Thereby, the amino acid residues 1 & 6 placenta will be out. o Has a critical role in lactation It is released in response to neural stimulation of receptors in ▪ Note: Prolactin is for production of milk; Lactation the birth canal and uterus, and of touch receptors in the breast means milk secretion from mammary gland It plays a role in hemostasis at the placental site following o Likely plays a major role in labor & parturition delivery ▪ Oxytocin extracts the uterus EDLET CHRISTINE S. DIONISIO | BSMT 3-3 55  LESSON 7: Therapeutic Drug Monitoring It stimulates muscle contraction on during delivery and 4- Polyphagia- occasional lactation- with bursts of oxytocin secretion occurring with anticipation of nursing or on hearing a baby cry. MAJOR TYPES OF DIABETES INSIPIDUS: Synthetic preparations: to increase weak uterine contraction a) TRUE DIABETES INSIPIDUS during labor and to aid in lactation (Hypothalamic/Neurogenic/Cranial/Central Diabetes Insipidus) ▪ It is deficiency of ADH with normal ADH receptor B). ANTIDIURETIC HORMONES (ADH)/ ARGININE ▪ It is due to failure of the pituitary gland to secrete ADH VASOPRESSIN (AVP) VASOPRESSIN ▪ There is a large volume of urine excreted (3-20L/day) a) A cyclic nonapeptide, structurally similar to oxytocin, with b) NEPHROGENIC DIABETES INSIPIDUS: an identical disulfide bridge; differs by only 2 amino acids ▪ It is characterized by having normal ADH but abnormal b) Major action is to regulate renal free water excretion & ADH receptor- renal resistance to ADH action water balance. ▪ It is due to failure of the kidneys to respond to normal c) A potent pressor agent & affects blood clotting or elevated ADH levels  Affects the endothelial lining and causes ▪ Nephrogenic DI is either congenital or acquired vasoconstriction to stop bleeding d) Hypothalamic osmoreceptors & vascular baroceptors DIAGNOSTIC TEST FOR DIABETES INSIPIDUS regulate release of vasopressin from posterior pituitary. Overnight Water Deprivation Test (Concentration Test) e) Deficiency can lead to diabetes insipidus, characterized by o Fasting: 10 pm onwards (8 to 12 hours) excessive urine production (polyuria) & intense thirst o After 8 to 12 hours without fluid intake, urine osmolality (polydipsia). does not rise above 300 mOsm/kg Diabetes insipidus: polyuria, polydipsia (sometimes +/- o In neurogenic DI, ADH levels are low and the kidney rapidly polyphagia) acts to conserve water in response to exogenous ADH Diabetes mellitus: polyuria, polyphagia & polydipsia administration o In nephrogenic DI, ADH levels are either normal or increase o Secreted by hypothalamus and stored in posterior pituitary and administration of additional ADH has little to no effect o Is a nonpeptide that acts on the distal convoluted and on renal water reabsorption collecting tubles of the kidneys o Major function: To maintain osmotic homeostasis by NOTES TO REMEMBER: regulating water balance Without ADH, urine osmolality is about 50 mOsm/kg while serum o It decreases the production of urine by promoting osmolality increases reabsorption of water by the renal tubules maintaining To establish diagnosis, the patient’s ability to produce water homeostasis concentrated urine must be tested o It increases blood pressure- a decrease in blood volume or If anything occurs to disrupt the thirst mechanism or prevent the blood pressure stimulate ADH release patient from drinking water, rapid development of o It is potent pressor agent and affects blood clotting by hypernatremia will occur promoting factor VII release from hepatocyte and factor VIII Syndrome of inappropriate antidiuretic hormone secretion (von Willebrands factor) release from the endothelium. (SIADH) refers to the sustained production of ADH in the absence o Physiologic stimuli to ADH secretion: nausea, cytokine, of known stimuli. It is characterized by decrease urine volume, hypoglycemia, hypercabia and nicotine low plasma osmolality, and normal or elevated urine sodium o Physiologic stimuli to ADH release: dehydration, physical levels (low serum electrolytes) and emotional stress due to major surgery o Potent physiologic stimuli to ADH release: emetic stimulus o Inhibitors of ADH release: ethanol, cortisol, lithium, and III. THYROID GLAND demeclocycline Produces 2 hormones o Reference value: 0.5- 2 pg/uL o Thyroid hormone: critical in regulating body metabolism, neurologic development, & other functions o Calcitonin: secreted by parafollicular C cells & involved in IN RELATION TO OSMOLALITY: calcium homeostasis Principal regulator of ADH secretion: increase plasma osmolality Conditions affecting thyroid hormone levels are much more ADH secretion is maximally stimulated at a serum osmolality of common than those affecting calcitonin. >295 mOsm/kg and suppressed when the osmolalility is less than 284mOsm/kg THYROID ANATOMY AND DEVELOPMENT A rise in effective osmolality shrinks the hypothalamic o Positioned in lower anterior neck & shaped like a butterfly o Made up of 2 lobes that rest on each side of trachea; band osmoreceptor cells, which then stimulate the thirst center in the of thyroid tissue (isthmus) runs anterior to trachea & cerebral cortex and stimulate ADH production in the supraoptic bridges lobes and paraventricular nuclei o Parathyroid glands: posterior to thyroid; regulate serum Conversely, a decline in effective osmolality causes swelling of calcium levels & recurrent laryngeal nerves that innervate the osmoreceptor cells, resulting in inhibition of ADH production vocal cords o Thyroid hormone is critical to neurologic development of CLINICAL DISORDERS: fetus. Diabetes Insipidus is deficiency of ADH; results in severe polyuria o Iodine is an essential component of thyroid hormone; (> 3L of urine /day) iodine deficiency leads to hypothyroidism, mental o Clinical picture includes: retardation, cretinism. 1- Normoglycemia o Congenital hypothyroidism occurs in 1 of 4,000 live births. 2- Polyuria with low specific gravity 3- Polydipsia (secondary polydipsia) EDLET CHRISTINE S. DIONISIO | BSMT 3-3 56