Medical brain notes 30

  DISORDERS OF THE ENDOCRINE SYSTEM INTRODUCTION The endocrine system is one of two major control systems in the body, the other being the nervous system, that help control the activities of the body. It consists of a number of ductless glands ( Figure 7.1 ) that produce hormones. Hormones are molecules that circulate in the blood and excite or inhibit the metabolic activity of target tissues or organs. These responses maintain and regulate body functions, such as growth and development, responses to stress and injury, reproduction, homeostasis and energy metabolism ( Figure 7.2 ). Hormones can be divided into three chemical groups: amines, peptides and proteins, and steroids ( Table 7.1 ). Many amine hormones, such as adrenaline (epinephrine) and those produced by the thyroid gland, are derivatives of tyrosine. The majority of hormones are peptides and proteins, examples being insulin and growth hormone. A number of protein hormones, for example thyroid stimulating hormone, are gl...

  HORMONE PRODUCTION Amine hormones include adrenaline, noradrenaline (also called epinephrine and norepinephrine respectively) and thyroid hormones. Their synthesis involves a series of enzyme-catalyzed reactions in the cytoplasm of endocrine cells. For example, thyroid hormones  are synthesized by iodination of tyrosine residues in the protein thyroglobulin found in the thyroid. Most peptide hormones are synthesized as large inactive prohormones, which are subsequently cleaved by enzymes to produce the active hormone. Sometimes a number of hormones may be derived from the same prohormone. Steroid hormones are synthesized by a sequence of enzymatic reactions using cholesterol as a common precursor. The enzymes responsible for conversion of cholesterol to hormone are located in the smooth endoplasmic reticulum and mitochondria of cells. The presence or absence of particular enzymes determines the type of steroid hormone synthesized by that specific cell.   Amine hormones,...

  MECHANISMS OF HORMONAL ACTION Hormones act by binding to specific receptors of target cells to form a complex ( Figure 7.6 ) that elicits a cellular response. Only the target tissue will express the receptor for a given hormone and be able to respond to it. Hormone receptors may be located on the surface of the cell or within the cell respectively. Hormones that bind to the former function through what are called second messenger systems, the hormone being the primary or first messenger. Second messengers are small  M r  water-soluble molecules and ions that are generally able to move freely throughout the cell. The most common secondary messengers are cyclic adenosine monophosphate (cAMP), the structurally related cyclic guanosine monophosphate (cGMP), Ca 2+ , inositol triphosphate (IP 3 ), and diacylglycerol (DAG) whose structures are shown in  Figure 7.7 . Extracellular receptors are transmembrane proteins that have an extracellular and an intracellular portion ...

  CAUSES OF ENDOCRINE DISORDERS Endocrine disorders arise because a disruption to the endocrine system causes decreased (hypofunction) or increased (hyperfunction) hormonal activity or resistance to hormone action. There may be defects in synthesis of the hormone due to an inherited deficiency of an enzyme required for its synthesis. Inappropriate stimuli may impair the release of the hormone or certain drugs may stimulate hormone release. Defects in the negative feedback mechanism may cause abnormal hormone secretion. Faulty inactivation or excretion of hormones in liver or renal diseases respectively can increase hormone levels. Excessive hormone secretion can occur ectopically from a nonendocrine source, such as a tumor. Even if correctly synthesized and released, the target tissues may not recognize the hormone because of a lack of receptors or because the receptors themselves are nonfunctional. Disorders will also occur if the target cells do recognize the hormone but there is...

  THE PITUITARY GLAND The pituitary gland is often referred to as ‘the master gland’ given that its secretions regulate the activities of many of the other hormone-producing glands. Despite its crucial role, it weighs only about 0.5 g. The pituitary is found in a bony cavity at the base of the skull and is connected to the hypothalamus by a pituitary stalk composed of blood vessels and nerve fibers. It is composed of two lobes, an anterior pituitary or adenohypophysis and a posterior pituitary or neurohypophysis ( Figure 7.12 ). The anterior pituitary secretes a number of hormones ( Figure 7.13 ) that are regulated by the release of peptides from the hypothalamus with stimulatory or inhibitory effects on the anterior pituitary. The principal peptides released by the hypothalamus reach the anterior pituitary by a portal blood circulation. These peptides include thyrotrophin releasing hormone (TRH), growth hormone releasing hormone (GHRH), gonadotrophin releasing hormone (GnRH), cort...

  DISORDERS OF PITUITARY FUNCTION The majority  of disorders in pituitary function are caused by tumors of the gland although some pituitary diseases can lead to underproduction of its hormones. Approximately 80% of pituitary tumors are functional, that is they cause an excessive secretion of hormones. The most common secrete prolactin, and account for 50% of functional tumors. The incidence of tumors affecting other hormones is 15% GH, 10% ACTH, 4% FSH/LH with less than 1% promoting TSH secretion. Large pituitary tumors may also exert pressure on nerves, causing headaches and visual disturbances. Radiological investigations such as X-rays, computer-aided tomography (CAT) scans and magnetic resonance imaging (MRI), outlined, are important in locating tumors and estimating their sizes. Prolactin secreting tumors, prolactinomas, cause hyperprolactinemia that, in turn, can lead to infertility in both males and females. Nonprolactin secreting tumors or pituitary stalk section by s...

  GROWTH HORMONE DISORDERS Growth hormone (GH) or somatotrophin promotes linear growth and the maintenance of tissues by stimulating the uptake of amino acids by cells, protein synthesis, increasing blood glucose concentration and fat metabolism and promoting epiphyseal bone growth. These effects are mediated by locally acting effectors called somatomedins that are synthesized by many tissues but particularly liver. Somatomedins stimulate cell proliferation and/or differentiation. They include insulin-like growth factors-I and II (IGF-I and IGF-II). Insulin-like growth factor-I is the most significant physiologically and, indeed, its concentration correlates with that of GH. Growth hormone is a polypeptide 191 amino acid residues long ( Figure 7.14(A)).  Approximately 70% of plasma GH is bound to growth hormone bindingprotein. Growth hormone is synthesized in the anterior pituitary gland in an inactive form called preprogrowth hormone that is hydrolyzed in several enzyme-catal...

  DIAGNOSIS AND TREATMENT OF GROWTH HORMONE DISORDERS A variety of tests are used to assess GH deficiency. Random measurements of serum GH are of limited value due to fluctuations in plasma GH levels in normal individuals. Urinary GH excretion is low in deficiency but obtaining an accurately timed collection of urine is difficult. Most tests rely on demonstrating that the hormone does not increase in concentration following a stimulus. Growth hormone increases after exercise and this has been used as a preliminary screening test. In the exercise test, the patient is subjected to hard physical exercise until they have a pulse rate greater than 150 beats per min . Blood is collected at 0, 2 and 20 min after stopping exercise. In normal individuals, the plasma concentration of GH increases by 20 mU dm –3  above the initial value. Growth hormone release increases during sleep, hence high values in a nocturnal sample may exclude deficiency. Blood samples are collected using a venou...

  THYROID HORMONE DISORDERS The thyroid gland is the largest endocrine gland in the body, weighing about 20 g. It is a bilobular organ that consists of microscopic spherical follicles with secretory cells ( Figure 7.16 ) that synthesize the thyroid hormones. Thyroid hormones ( Figure 7.17 (A)  and  (B) ) consist of triiodothyronine (T 3 ) and thyroxine (T 4 ). Triiodothyronine is the most active, four times that of T 4 , and has a half-life of 1.5 days compared with 9 days for T 4 . However in most tissues, particular the liver, T 4  can be readily converted to T 3 . More than 99% of T 3  and T 4  are transported in the serum as complexes: 70% to thyroxine binding globulin (TBG) and about 20% to albumin and around 10% to prealbumin. The remaining small free portion is the metabolically active fraction. The effects of thyroid hormones are to increase heat production, oxygen consumption, the metabolism of proteins, fats and carbohydrates and to promote normal...