L10. Disorders of Endocrine Function PDF

Disorders of Endocrine Function Outlines: Anatomy and Physiology Components of the endocrine system Major functions Hormones Disorders: o Hyperthyroidism and Hypothyroidism o Addison’s disease (adrenal hypofunction) o Cushing’s syndrome o Diabetes insipidus o D...

Disorders of Endocrine Function Outlines: Anatomy and Physiology Components of the endocrine system Major functions Hormones Disorders: o Hyperthyroidism and Hypothyroidism o Addison’s disease (adrenal hypofunction) o Cushing’s syndrome o Diabetes insipidus o Diabetes mellitus o Syndrome of inappropriate antidiuretic hormone secretion 2  Objectives: By the end of this lecture, the students will be able to: Identify 3-4 components of the endocrine system Explain the pathophysiology of Cushing’s syndrome List 3-4 causes of Syndrome of inappropriate antidiuretic hormone secretion Differentiate between diabetes insipidus and diabetes mellitus 3 Anatomy and Physiology Glands are organs that manufacture and secrete chemical substances. Glands may be endocrine or exocrine. Exocrine glands secrete chemicals to the outer surface of the body (i.e., sweat and tears) or into a body cavity (i.e., saliva and pancreatic digestive enzymes). Endocrine glands secrete chemical hormones into the bloodstream. These chemicals travel to and act upon various tissues, where they signal and affect target cells that have appropriate receptors. They then act on these cells to cause a specific cell function. The network of endocrine glands that secrete hormones throughout the body is collectively referred to as the endocrine system. 4 Components of the endocrine system The major components of the endocrine system include the Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pancreas (both an endocrine and exocrine gland) The reproductive organs (ovaries in women and testes in men). 5  Gland location Function Pituitary gland Below the brain Controls many functions of the other endocrine glands In front of the neck, below the Thyroid gland Plays an important role in the body's metabolism larynx (voice box) In front of the neck, below the Play an important role in the regulation of the body's calcium Parathyroid glands larynx (voice box) balance. Work hand-in-hand with the hypothalamus and pituitary gland. Adrenal glands On top of each kidney make and release corticosteroid hormones and epinephrine that maintain blood pressure and regulate metabolism Plays a role in digestion, as well as hormone production. Across the back of the Pancreas Hormones produced by the pancreas include insulin and abdomen, behind the stomach. glucagon, which regulate levels of blood sugar. The reproductive Female and male reproductive Produce egg cells, estrogen and progesterone organs system produce testosterone and sperm 7 Major functions The endocrine system regulates metabolic processes of the body. The primary functions of the endocrine glands include the following: Regulating metabolism Regulating reproduction Controlling the balance of extracellular fluid and electrolytes (sodium, potassium, calcium, and phosphates) Maintaining an optimal internal environment such as regulation of blood glucose levels Stimulating growth and development during childhood and adolescence 8 Hormones Hormones released by these glands regulate homeostasis, reproduction, growth, development, and metabolism by transmitting messages directly to receptors located on their respective target organs. A complex system of feedback loops work together to maintain balanced levels of all hormones. Levels of hormone secretion may be regulated by either positive or negative feedback mechanisms. Increased levels of a particular hormone will inhibit secretion, and decreased levels of a particular hormone will stimulate secretion. 9 10  HYPERTHYROIDISM Hyperthyroidism, or thyrotoxicosis, is a metabolic imbalance that results from the overproduction of thyroid hormone. The most common form is Graves’ disease, which increases thyroxine (T4) production, enlarges the thyroid gland (goiter), and causes multiple system changes. CAUSES Excessive dietary intake of iodine Defect in suppressor T-lymphocyte function permitting production of autoantibodies Medications, such as amiodarone antiarrhythmic Stress, such as surgery, infection, toxemia of pregnancy Toxic nodules or tumors 11 PATHOPHYSIOLOGY Autoimmune disorder in which antibodies that mimic the role of TSH produce an increase in secretion of thyroid hormones. Other causes of hyperthyroidism include acute intoxication with exogenous thyroid hormones, and (less commonly) as a result of drugs with high iodine loads such as amiodarone or iodinated IV contrast, which may precipitate sudden release of excess thyroid hormones in susceptible individuals. A goiter is an enlarged thyroid gland, either the result of increased stimulation or a response to increased metabolic demand Signs and Symptoms Enlarged thyroid (goiter) , apprehension, heart palpitations, and weight loss , heat intolerance and increased sweating caused by this hypermetabolic state are frequent symptoms 12  HYPOTHYROIDISM Hypothyroidism is an endocrine dysfunction characterized by decreased or absent secretion of thyroid hormones. Hypothyroidism is more prevalent in women in than men CAUSES ▪ After thyroidectomy or radiation therapy ▪ Pituitary fails to produce thyroid stimulating hormone -TSH ▪ Iodine deficiency (usually dietary) ▪ Use of some antithyroid medications SIGNS AND SYMPTOMS Weakness, fatigue, forgetfulness, sensitivity to cold, unexplained weight gain Coarse hair and skin, neurologic changes such as altered mental status Cardiovascular symptoms like decreased cardiac output, bradycardia etc 13 PATHOPHYSIOLOGY Defective thyroid hormone secretion is classified as either primary or secondary hypothyroidism. Primary hypothyroidism involves direct thyroid injury caused by an autoimmune disorder or an adverse drug reaction. Eg:Patients who have had surgical thyroidectomy or radioablation therapy In secondary hypothyroidism, damage to the hypothalamus or pituitary gland results in decreased stimulation of the thyroid gland (specifically, a decline in the production and release of TSH). 14 ADDISON’S DISEASE (ADRENAL HYPOFUNCTION) Hypofunction of the adrenal gland Types: 1. Primary adrenal hypofunction :(Addison’s disease) - originates within the adrenal gland. Eg:Adrenalectomy. Characterized by the decreased secretion of mineralocorticoids, glucocorticoids, and androgens. 2. Secondary adrenal hypofunction is due to a disorder outside the gland such as impaired pituitary secretion of corticotropin. Characterized by decreased glucocorticoid secretion. 15 PATHOPHYSIOLOGY Addison’s disease involves all zones of the cortex, causing deficiencies of adrenocortical secretions, glucocorticoids, androgens, and mineralocorticoids. Manifestations of adrenocortical hormone deficiency become apparent when 90% of the functional cells in both glands are lost. ❖ Cortisol deficiency causes low blood glucose levels ❖ Aldosterone deficiency causes increased renal sodium loss and enhances potassium reabsorption ❖ Androgen deficiency may decrease hair growth in axillary and pubic areas Sign and Symptoms Hyperpigmentation of skin and mucous membranes, Low blood sugar, Fatigue, Malaise, Loss of appetite Addisonian crisis - potentially life threatening condition, occurs when the patient with addison's disease faces extreme physical stress and trauma & does not get extra steroid to cover their body needs to meet that trauma. Symptoms include extreme weakness, fatigue, drop in blood pressure, dehydration etc 16 CUSHING’S SYNDROME A cluster of clinical abnormalities caused by excessive adrenocortical hormones (particularly cortisol) CAUSES Anterior pituitary hormone (corticotropin) excess Autonomous, ectopic corticotropin secretion by a tumor outside the pituitary gland Excessive glucocorticoid administration, including prolonged use 17 PATHOPHYSIOLOGY Cushing’s syndrome is caused by prolonged exposure to excess glucocorticoids. Cortisol excess results in anti-inflammatory effects and excessive catabolism of protein and peripheral fat to support hepatic glucose production. Excess cortisol suppresses the hypothalamic-pituitary-adrenal axis Sign and Symptoms Diabetes mellitus due to cortisol induced insulin resistance Muscle weakness due to hypokalemia or loss of muscle mass from increased catabolism Purple striae, facial plethora (edema and blood vessel distention) Buffalo hump,moon face, truncal obesity 18 19 DIABETES INSIPIDUS A disorder of water metabolism, results from a deficiency of circulating vasopressin (also called antidiuretic hormone [ADH]) or from renal resistance to this hormone. CAUSES Acquired, familial, idiopathic, neurogenic, or nephrogenic Associated with stroke, hypothalamic or pituitary tumors, and cranial trauma or surgery Certain drugs, such as lithium 20 PATHOPHYSIOLOGY Neurogenic is an inadequate response of ADH to plasma osmolarity, which occurs when an organic lesion of the hypothalamus, infundibular stem, or posterior pituitary gland partially or completely blocks ADH synthesis transport, or release Nephrogenic diabetes insipidus is caused by an inadequate renal response to ADH Psychogenic diabetes insipidus is caused by an extremely large fluid intake Sign and Symptoms Polydipsia with fluid intake of 5 to 20 L/day, Polyuria with urine output of 2 to 20 L/24-hour period of dilute urine, Nocturia, leading to sleep disturbance and fatigue, Low urine specific gravity less than 1.006 21 DIABETES MELLITUS Diabetes mellitus is a metabolic disorder characterized by hyperglycemia (elevated serum glucose level) resulting from lack of insulin, lack of insulin effect, or both. Three general classifications are recognized: Type 1, absolute insulin insufficiency Type 2, insulin resistance with varying degrees of insulin secretory defects Gestational diabetes- woman not previously diagnosed with diabetes shows glucose intolerance during pregnancy CAUSES Environment (infection, diet, toxins, stress) Heredity Lifestyle changes in genetically susceptible personss, which emerges during pregnancy. 22 PATHOPHYSIOLOGY Type 1 diabetes- a triggering event, possibly a viral infection, causes the production of autoantibodies against the beta cells of the pancreas leading to a decrease in and ultimate lack of insulin secretion. Type 2 diabetes mellitus is a chronic disease caused by one or more of the following factors: impaired insulin secretion, inappropriate hepatic glucose production, or peripheral insulin receptor insensitivity. Gestational diabetes mellitus occurs when placental hormones counteract insulin, causing insulin resistance. Sign and Symptoms The classic clinical manifestations of diabetes mellitus are referred to as the three Ps: polyuria, polydipsia, and polyphagia. Weight loss, thirst, blurred vision, and fatigue may also be present 23 SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION (SIADH) Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition in which the body makes too much antidiuretic hormone (ADH). This hormone helps the kidneys control the amount of water your body loses through the urine. SIADH causes the body to retain too much water. PATHOPHYSIOLOGY In the presence of excessive ADH, excessive water reabsorption from the distal convoluted tubule and collecting ducts causes hyponatremia and normal to slightly increased extracellular fluid volume. This may lead to complications, such as cerebral edema, brain herniation etc. 24 Causes: Any cause that results in too much ADH in the body can lead to SIADH. Oat cell carcinoma of the lung (most common), which secretes excessive levels of ADH or vasopressin like substances Drugs that either increase ADH production or potentiate ADH action, such as antidepressants. Central nervous system disorders, including brain tumor Disorders of the brain, such as injury, infections, stroke Sign and Symptoms Thirst, anorexia, fatigue, and lethargy Weight gain, edema, water retention, and decreased urine output due to hyponatremia 25