FOCUS: ENDOCRINOLOGY Endocrinology Review – Adrenal and Thyroid Disorders LINDA S. GORMAN, JANELLE M. CHIASERA LEARNING OBJECTIVES This article represents the first of three articles focusing 1. Define endocrinology and list the major endocrine on the endocrine system. The first article will provide glands of the body. you with fundamental theory regarding the endocrine system that will serve as a basis for understanding the 2. Explain how feedback (positive and negative) Downloaded from promotes maintenance of normal levels of next two articles focusing on two specific endocrine hormones. glands, the thyroid and adrenal glands. 3. Differentiate between steroid and peptide hormones with regard to their mechanism of Endocrinology is the branch of medical science that action. deals with the endocrine system, a system that consists 4. Provide examples of peptide and steroid hormones. of several glands located in different parts of the body http://hwmaint.clsjournal.ascls.org/ 5. Explain how endocrine disorders are categorized. that secrete hormones directly into the bloodstream. Although every organ system in the body may respond ABBREVIATIONS: ACTH - adrenocorticotropic hor- to hormones, endocrinology focuses specifically on mone; ADH - antidiuretic hormone; CRH – cortico- endocrine glands whose primary function is hormone tropin releasing hormone; DHEA – dehydroepian- secretion. Major endocrine glands include the pituitary drosterone; FSH - follicle stimulating hormone; GHRH (anterior and posterior), hypothalamus, thyroid, - growth hormone releasing hormone; GnRH – gona- parathyroid, pineal, pancreas, adrenal (cortex and dotropin releasing hormone; HPT - hypothalamus, medulla), and gonads (ovaries and testes). Figure 1 pituitary, target gland; LH - luteinizing hormone; shows the various locations of endocrine glands. MBST - membrane-bound signal transducer; SRE - on September 28 2021 steroid response element; TRH - thyrotropin releasing hormone; TSH - thyroid stimulating hormone INDEX TERMS: Endocrine Glands, Hormones, Hy- drocortosone, Hypoalamo-hypophyseal System, Pitui- tary-Adrenal System, Stress Clin Lab Sci 2013;26(2):107 Linda S. Gorman, PhD, MLS (ASCP)CM, University of Kentucky, Lexington, KY Janelle M. Chiasera, PhD, MT (ASCP), University of Alabama at Birmingham, Birmingham, Alabama Address for Correspondence: Linda S. Gorman, PhD, Figure 1. Location of the Major Endocrine Glands. Image reprinted MLS (ASCP)CM, CLS Education Co-ordinator, Associate with permission of John Nagy. Professor, 900 S. Limestone Ave, Rm 126G CTW, University of Kentucky, Lexington, KY 40536-0200, The HPT Axis (859)-218-0855, [email protected] The endocrine system is part of the body’s extracellular communication system that links the brain to various VOL 26, NO 2 SPRING 2013 CLINICAL LABORATORY SCIENCE 107 FOCUS: ENDOCRINOLOGY parts of the body and acts to control body metabolism, Releasing Hormone (CRH), which affects adrenal growth and development, and reproduction. The hormones, to ones that foster sexual characteristics production and circulating levels of hormones are (Gonadotropin Releasing Hormone) and growth controlled by means of a feedback process that links the (Growth Hormone Releasing Hormone). Our focus hypothalamus to the pituitary and the pituitary to a here is on the thyroid and adrenal glands so we will target gland. This linkage is referred to as the leave the other hypothalamic hormones for others to hypothalamus, pituitary, target gland (HPT) axis.1,2 discuss. (Figure 2, Table 1.) Refer to Figure 2. Table 1. Releasing Hormones and Their Effect on Pituitary and Target Glands Hypothalmus Releases trophic homormones that lead to release of smulators Hypothalamic Cellular Target/Pituitary Target Gland/Target Hormone Gland Hormone Gland Hormone(s) Downloaded from Pituitary Corticotropin Releasing Corticotroph/ Adrenal gland Hormone (CRH) ACTH (Cortisol) Smulang hormones are released that target the gland of interest Thyrotropin Releasing Thyrotroph/TSH Thyroid Gland/ Hormone (TRH) T3 and T4 Target gland http://hwmaint.clsjournal.ascls.org/ Growth Hormone Somatotroph/GH All tissues Once smulated, the gland releases the hormone for target Releasing Hormone (GHRH) Figure 2. Hypothalamus, Pituitary, Target Gland (HPT) axis Gonadotropin Releasing Gonadotroph/ Gonads/Testosterone Hormone (GnRH) LH and FSH and Estrogen In general terms, hormones are produced by specialized glands in one part of the body and travel through the bloodstream to result in a biological effect at a distant In the hypothalamus the tropic releasing hormones site. The hypothalamus is considered to be the “master come from neurons in the anterior hypothalamus and gland” of this axis as it takes signals from cortical are released thru the portal veins to the pituitary inputs, autonomic function, and other environmental sinusoids. The hypothalamic hormones stimulate the on September 28 2021 triggers and delivers signals (via releasing hormones) to selective pituitary release of hormones, often called 4 target cell types in the pituitary gland. The pituitary “stimulating hormones”. The pituitary stalk links the gland responds by releasing hormones that act on target posterior pituitary with the part of the hypothalamus glands to produce specific target gland hormones. For that secretes anti-diuretic hormone (ADH) and 4 example, thyrotrophin releasing hormone (TRH) oxytocin. These hormones are associated with the produced by the hypothalamus acts on thyrotroph cells posterior pituitary and not of interest here. of the pituitary gland to produce thyroid stimulating hormone (TSH). Thyroid stimulating hormone acts The Thyrotrophic releasing hormone (TRH) and directly on the thyroid gland (target gland) to produce Corticotrophic releasing hormones of the hypothalamus thyroid hormones. Refer to Table 1 for other examples are released into the hypothalamic portal vein system of releasing hormones and their effect on pituitary and that is separate from the general human circulatory target glands.1,2 system. These releasing hormones can travel thru the portal veins to the pituitary without being evident in 4 The hypothalamus gland is located in the brain above the venous blood. Once the tropic hormones enter the the brain stem and below the thalamus.3 In humans, the pituitary sinusoids they can stimulate the pituitary to hypothalamus is the size of an almond. Its functions produce/secrete specific stimulating hormones, such as include releasing the trophic hormones called “releasing Thyroid Stimulating Hormone (TSH) if the hormones”. These trophic hormones span from hypothalamus sends TRH or Adenocorticotropic Thyrotropin Releasing Hormone (TRH), which affects hormone (ACTH) if the hypothalamus sends CRH. the release of thyroid hormones, Corticotropin (Figures 3 and 4) 108 VOL 26, NO 2 SPRING 2013 CLINICAL LABORATORY SCIENCE FOCUS: ENDOCRINOLOGY Mechanism of Action Hypothalmus All hormones act on their specific glands/tissues Corticotropin Releasing Hormone or CRH through receptors located on the surface or within the cytosol of the cell. The binding between the hormones and the receptor serves as an initial signal resulting in a Pituitary cascade of events that result in the production of a Adrenocorticotropic Hormone or ACTH protein. Hormones are divided into two broad categories, peptide (water soluble) and steroid (water insoluble). Refer to Table 2. While all hormones react Adrenal Gland (cortex) with receptors, their mechanism of action varies Cortisol hormone depending on how they are categorized. Because they are water soluble, peptide hormones must interact with receptors that are located at the surface of the cell. Once Downloaded from Figure 3. Adrenal gland stimulation to produce cortisol hormone. bound to its receptor, the hormone receptor complex activates a membrane-bound signal transducer (MBST). Hypothalmus Often this signal transducer is guanine nucleotide- yroid Releasing Hormone or TRH binding regulatory protein, also called the G-protein complex. The MBST is coupled to the adenylate cyclase http://hwmaint.clsjournal.ascls.org/ and phospholipase enzyme systems and once activated Pituitary results in the production of a peptide hormone. Due to yroid Stimulating Hormone or TSH their water insoluble nature, steroid hormones may diffuse across the surface of the cell membrane and bind to their receptors in either the cytoplasmic or nuclear yroid gland fractions of the cells. Once the steroid hormone binds yroid T4 yroid T3 to its receptor, the receptor undergoes a conformational change resulting in activation of the entire hormone receptor complex. The activated complex has an Figure 4. Thyroid stimulation by TSH to produce thyroid increased affinity for chromatin at a site referred to as hormones T4 and T3. the steroid response element (SRE). The SRE binding on September 28 2021 ultimately causes the production of the nuclear product- The Pituitary -a specific protein.6,7 Peptide hormones are synthesized The pituitary gland, with its stimulating hormones, is as preprohormones and are packaged into secretory like a bus stop or railroad station. The pituitary takes in vesicles providing a ready available storage pool of the messages from hypothalamic released hormones and hormones to draw from. Steroid hormones, on the responds by sending out its own stimulating hormones. other hand, are all produced from cholesterol and are By itself the pituitary is the size of a pea5 and is located available bound to proteins. Because they are protein between the two