PHARMACOLOGY EXAM 4 INTRODUCTION TO ENDROCRINOLOGY

The endocrine system, also referred to as the hormone system, is a series of glands located throughout the body that functions to maintain homeostasis. By modulating the release of chemical messengers (hormones), the endocrine system is able to send signals to regulate organ functions. The endocrine system is unique in that it works through hormones that generally have a longer and slower onset and duration of action. There are actually eight endocrine glands throughout the body including: the pineal, pituitary, thyroid, thymus, adrenal, pancreas, ovary and testis. Each of these glands releases a hormone into the body that is responsible for regulating growth, metabolism, or reproduction. This module will focus on select glands such as the pituitary gland, thyroid gland, and adrenal cortex and the pharmacologic options available when they fail to work properly. Physiology Overview The pituitary gland is sometimes called the “master gland” because it controls many of the other glands within the endocrine system. The pituitary gland is located in the region of the forebrain near the hypothalamus. Hormones released from the pituitary gland work by a negative feedback loop. This means the pituitary gland releases a hormone that signals an endocrine gland to release a subsequent hormone. The presence of this subsequent hormone then signals back to the pituitary gland to stop releasing the original hormone. The pituitary gland has two lobes, the anterior pituitary gland and the posterior pituitary gland. As outlined in Table 4.1, each lobe secretes its own distinct hormones. Table 4.1 Hormones of the Pituitary Gland Anterior Pituitary Gland Posterior Pituitary Gland PHARMACOLOGY EXAM 4 INTRODUCTION TO ENDROCRINOLOGY Adrenocorticotropic Hormone (ACTH) Follicle Stimulating Hormone (FSH) Growth Hormone (GH) Luteinizing Hormone (LH) Prolactin (PH) Thyroid Stimulating Hormone (TSH) Antidiuretic Hormone (ADH) Oxytocin Pathophysiology and Related Drug Therapy Pituitary Generally, medications that affect the pituitary gland are being used as replacements for a hormone deficiency within the body. Examples of medications used to treat a pituitary hormone deficiency include (1) Somatropin (2) Octreotide, (3) Vasopressin and (4) Desmopressin. Somatropin- mimics the effects of growth hormone (GH) by promoting growth within the body. Typically, somatropin is used in children to promote linear growth when they do not produce a sufficient amount of endogenous hormone on their own. Octreotide- inhibits GH release and is structurally similar to the body’s GH release-inhibiting factor or somatostatin. It is useful in the treatment of severe watery diarrhea resulting from slow growing tumors because it reduces the concentration of the protein that causes the diarrhea. Vasopressin- is a potent vasoconstrictor and mimics the actions of the body’s antidiuretic hormone (ADH). It works by increasing water reabsorption in the distal tubule and collecting duct of the nephron (see Module 3). This can reduce water excretion up to 90%. It is also an especially effective vasoconstrictor in higher doses and can be used in emergency situations when blood pressure is dropping dangerously low. Desmopressin- is a synthetic vasopressin. As such, it also mimics ADH and works to increase water reabsorption in the nephron. Additionally, desmopressin shows dose-dependent activity on clotting factors, making it useful in treating certain blood disorders. Thyroid The thyroid gland is located in the neck and is responsible for the regulation of the body’s metabolism through the release of the following hormones: Thyroxine (T4) and triiodothyronine (T3). Thyroid Stimulating Hormone (TSH) is the endogenous substance that the pituitary gland secretes to control the release of these thyroid gland hormones. There are two main problems that can occur in the thyroid gland: (1) Hypothyroidism and (2) Hyperthyroidism. Hypothyroidism- A common condition characterized by diminished production of the thyroid hormones (Thyroxine (T4) and triiodothyronine (T3)). Symptoms of this condition include cold intolerance, unintentional weight gain, depression, dry brittle hair and nails, and fatigue. Overall, think of the symptoms as a decrease in the body’s metabolism resulting in an overall slowing. Hypothyroidism is when there is a decrease in thyroid hormones (T3 and T4). Since TSH is the endogenous substance that the pituitary gland secretes to control the release of T3 and T4, in hypothyroidism the TSH level is actually higher than normal. This is because the thyroid hormones are low and so the pituitary is releasing additional TSH to signal an increase in thyroid hormones. Drug Therapy- The treatment for hypothyroidism is relatively straight forward. It is to provide thyroid hormone replacement to the patient. While there are natural and synthetic options available, the synthetic levothyroxine (synthetic T4) is used in the majority of patients. Essentially, levothyroxine works in the same manner as the endogenous hormones. By taking levothyroxine, the deficiency is corrected. Levothyroxine is the drug of choice in most cases due to its predictable effects and long enough half-life to allow for once daily dosing. However, it can be impacted by food or drugs, so it is recommended to take on an empty stomach 30-60 minutes prior to breakfast. Hyperthyroidism- A condition characterized by excessive production of the thyroid hormones (T3 and T4). In contrast to hypothyroidism, hyperthyroidism causes an overall increase in the body’s metabolism. Symptoms of this condition include diarrhea, flushing, increased appetite, muscle weakness, fatigue, palpitations, irritability, nervousness, heat intolerance, and altered menstrual flow. Hyperthyroidism is when there is an increase in thyroid hormones (T3 and T4). In this case the high levels of thyroid hormone signal the pituitary gland to stop releasing TSH. This in turn signals the body to make less thyroid hormone since there is too much. Drug Therapy- Propylthiouracil (PTU) and Methimazole are two anti-thyroid drugs available that work by inhibiting the formation of the thyroid hormones. Two weeks of PTU therapy may be needed prior to symptom improvement. On the other hand, Methimazole, is rarely used clinically. It is also important to note that is some cases where drug therapy is ineffective, or the patient is unable to tolerate treatment, surgical resection of the thyroid gland is often performed. Such a patient would be then considered to have hypothyroidism and would need thyroid hormone replacement for the rest of their life. Adrenal Glands The adrenal glands are located on the upper surface of each kidney. Although there are two parts of the adrenal glands, the adrenal medulla (the inner part) and the adrenal cortex (the outer part), the focus will be on the adrenal cortex in this section. The hormones released by the adrenal cortex are generally referred to as corticosteroids or just steroids. Importantly, there are two distinct types of corticosteroids: (1) glucocorticoids and (2) mineralocorticoids, Glucocorticoids are critical to the body’s overall function and work to stimulate the production of glucose (gluconeogenesis) and the breakdown of proteins (catabolism). When the body undergoes any type of stress including trauma or surgery, the need for glucose increases. For tissues to be able to repair glucose is a necessary component. Two specific glucocorticoid hormones exist and can be released in the form of either cortisol or cortisone. When there is a deficiency in glucocorticoids, a person is said to have Addison’s disease. Conversely, when a person is producing excess glucocorticoids, the patient is said