Lesson 1 Unit 2 – Endocrine Pathophysiology

Lesson 1 Unit 2 – Endocrine Pathophysiology 1 Unit 2 Study Guide Terms Associated with Endocrine Disease Hyposecretion - If a gland is secreting too little hormone because it itself is unable to function normally, the disorder is called primary hyposecretion. Causes could be genetic lack of an enzyme, dietary deficiency of a precursor, infection etc.  If a gland is secreting too little hormone because there is too little tropic hormone to stimulate it, the disorder is called secondary hyposecretion. Hypersecretion - Primary hypersecretion is a gland itself secreting too much hormone while secondary hypersecretion is the excessive stimulation of a gland by its tropic hormone. Hyporesponsiveness - Target cells do not respond to the hormone due to a deficiency of receptors, a defect in the signal transduction mechanism or a deficiency of an enzyme that catalyzes the activation of the hormone.  In diabetes mellitus, the target cells of the hormone insulin are hyporesponsive. Hyperresponsiveness - Hypersecretion of thyroid hormones can lead to hyperresponsiveness to epinephrine and a consequent increase in heart rate. Endocrine Disorder Etiologies Functional disorders • Caused by non-endocrine disease such as chronic renal failure, liver disease, or heart failure Tissue resistance • Occurs when target tissue fails to respond to a hormone (hormone resistance or target tissue resistance) Iatrogenic • Induced by medical treatments such as chemotherapy, radiation therapy, or surgical removal of glands • Treatment for endocrine hyperfunction involves removal or destruction of glandular tissue with resultant chronic hypofunction Lesson 1 Unit 2 – Endocrine Pathophysiology • Chronic hormone replacement therapy may be required Congenital • Inborn genetic defect that causes excessive production of hormone precursors Autoimmune • Involves genetic predisposition and environmental trigger; antibodies made against antigens on self-tissue cells Neoplastic • Hormones may be produced by abnormal tissue sites (ectopic) such as malignancies Classifications of Endocrine Disorders • In primary, gland fails, inadequate hormone produced, low levels of circulating hormone, but blood levels of the corresponding trophic pituitary hormone levels very elevated • In secondary, pituitary gland fails to release trophic hormone, secondarily reducing primary gland production, so both levels are abnormally low Types of Endocrine Disorders Anterior Pituitary Growth Hormone (GH) • Hypersecretion - Gigantism in children - Acromegaly in adults - • Gigantism (acromegaly) and other growth hormone problems. If the pituitary gland produces too much growth hormone, a child's bones and body parts may grow abnormally fast. If growth hormone levels are too low, a child can stop growing in height. Hyposecretion - Pituitary dwarfism Clinical manifestations in GH deficiency include hypoglycemia, irregular setting of teeth, thin hair, poor nail growth, greater fat mass, decreased muscle mass, delayed bone formation, delayed puberty, decreased bone density, hypercholesterolemia. 2 Lesson 1 Unit 2 – Endocrine Pathophysiology 3 Treatment: GH replacement therapy Posterior Pituitary ADH (anti-diuretic hormone)  Hypersecretion - SIADH (Syndrome of inappropriate ADH secretion): Excess ADH stimulates renal tubules to reabsorb water despite decreased blood osmolality - Adrenal insufficiency and hypothyroidism can cause increased ADH secretion and hyponatremia Clinical manifestations include hyponatremia (abnormally low level of sodium in blood, associated with dehydration), increased plasma volume, increased sodium excretion.  Hyposecretion - Diabetes insipidus: The posterior pituitary gland does not produce enough ADH and thus, too much water leaves the body through the kidneys - Constant thirst and urination Clinical manifestations include polyuria (excessive flow of watery urine), polydipsia (excessive constant thirst), nocturia (excessive urination at night), hypernatremia (excessive amounts of sodium in blood), dry mucous, poor skin turgor, disorientation, etc. Thyroid gland Thyroid Stimulating Hormone (TSH) • Hypersecretion - The thyroid gland produces too much thyroid hormone, leading to weight loss, fast heart rate, sweating, and nervousness. The most common cause for an overactive thyroid is an autoimmune disorder called Grave's disease. Grave’s disease: enlarged thyroid (goiter) - Because the body’s metabolism is increased, people often feel hotter than those around them and can slowly lose weight even though they may be eating more. - The weight issue is confusing sometimes since we often think of people who eat more as gaining weight. - Thyroid storm. - IMPORTANT: Only a small percentage of goiters produce too much thyroid hormone, the majority of thyroid goiters actually become large because they are NOT producing enough thyroid hormone. Lesson 1 Unit 2 – Endocrine Pathophysiology 4 Clinical manifestations include palpitations (rapid heart beat), heat intolerance, nervousness, insomnia, fatigue, breathlessness, weight loss, muscle weakness. Thyroid storm: Life-threatening thyrotoxicosis. Occurs when excessive release of amounts of thyroid hormones. Elevated temp, tachycardia, arrhythmias, congestive heart failure. Treatment: surgical removal of portion of the over-secreting thyroid. Administration of radioactive iodine. Use of antithyroid drugs. • Hyposecretion - Primary failure of thyroid gland (majority due to intrinsic thyroid gland dysfunction) - Secondary to a deficiency of TRH, TSH, or both (associated with head/brain conditions) - The thyroid gland does not produce enough thyroid hormone, leading to fatigue, constipation, dry skin, and depression. The underactive gland can cause slowed development in children. Some types of hypothyroidism are present at birth. - Cretinism (idiocy, accompanied by physical degeneracy deformity) - Autoimmune thyroiditis (Hashimoto’s thyroiditis) (inflammation of thyroid) - Inadequate dietary supply of iodine - Myxedema (severe or prolonged hypothyroidism) generalized non-pitting edema, decreased level of consciousness, hypotension, hypothermia. Clinical manifestations include fatigue, weakness, weight gain or decreased difficulty losing weight, cold intolerance, muscle cramps, constipation, depression, memory loss, decreased libido. Treatment: Hormone replacement (typically T4) Condition TSH level T4 level Normal Normal Normal Hyperthyroidism Primary Hypoth. Second. Hypo. Low High Low High Low Low Lesson 1 Unit 2 – Endocrine Pathophysiology 5 Parathyroid Gland • Hyperparathyroidism - Bone deformity and fractures Calcium stones in urinary tract Clinical manifestations include kidney stones, bone demineralization (osteoporosis), polyuria, dehydration, anorexia, nausea, vomiting, constipation, bradycardia, heart block, and cardiac arrest. – Manifestations result from high serum calcium levels and bone demineralization – High serum calcium levels decrease neuromuscular excitability • Hypoparathyroidism - Severe muscle tetany due to decreased calcium levels Clinical manifestations include circumoral numbness (mouth numbess), paresthesias of the distal extremities (tingling sensation), muscle cramps, spasms, fatigue, hyperirritability, anxiety, depression. – Manifestations result from low serum calcium levels; increased neuromuscular excitability Lesson 1 Unit 2 – Endocrine Pathophysiology 6 Adrenocortical Insufficiency • Primary: hyposecretion due to disease of adrenal cortex; idiopathic or autoimmune (Addison disease), surgical removal • Secondary: inadequate secretion of ACTH; usually iatrogenic, related to corticosteroid therapy (suppresses ACTH) – Sudden withdrawal of corticosteroids • Tertiary: hypothalamic malfunction/injury • Cortisol insufficiency is most clinically relevant Clinical manifestations include Early signs include anorexia, weight loss, salt-wasting, weakness, malaise, apathy, electrolyte disturbances, hyperpigmentation of skin, hypoglycemia, and hyperkalemia. Diminished vascular tone, reduced cardiac output, inadequate circulating blood volume, low blood pressure; can lead to cardiovascular collapse. Treatment: Intravenous glucocorticoids and volume replacement Adrenal Gland Disorders Corticosteroids • Hypersecretion - Cushing’s Syndrome: Changes in carbohydrate and protein metabolism; Resulting in a puffy appearance, other changes include a “buffalo hump” and a “moon face” Clinical manifestations include round face with flushed cheeks “moon face”. Weight gain with excess total body fat, particularly in the abdomen, thin extremities. Cervical fat pad, capillary friability, thin skin with formation of purple striae and ecchymosis over the abdomen, arms, and thighs. Decreased muscle mass, muscle weakness. Glucose intolerance, hyperglycemia. Hypertension (salt-retaining activity of cortisol), demineralization of bone (osteoporosis) increased androgen production causing excessive hair, acne, menstrual irregularities. Lesson 1 Unit 2 – Endocrine Pathophysiology 7 Adrenal Medulla Disorder • Hypersecretion - Pheochromocytoma: adrenal medulla tumor resulting in excessive production and release of catecholamines Clinical manifestations include hypertension (persistent or intermittent), headache, tachycardia, diaphoresis, tremor, nervousness, emotional lability, pallor, fatigue, orthostatic hypotension. Disorders of the Pancreas • Hyperinsulinism - Too much insulin released or too much insulin administered. In pancreatic cancer, the tumor may cause an overproduction of insulin. - Hypoglycemia: abnormally low blood sugar usually resulting from excessive insulin or a poor diet - Usually the result of an overdose of insulin Precipitating factors include error in dosage, failure of patient to eat, increased exercise from normality, medication changes, and use of alcohol. • Hypoinsulinism - Diabetes mellitus caused by a relative or absolute deficiency of insulin and characterized by polyuria. Lesson 1 Unit 2 – Endocrine Pathophysiology 8 Somogyi Effect • The Somogyi Effect is seen when there is a tendency of the body to react to extremely low blood sugar by overcompensating, resulting in high blood sugar. The Somogyi effect, also known as the “rebound” effect. When blood glucose levels drop too low, the body sometimes reacts by releasing glucagon and epinephrine (counterregulatory hormones). These hormones cause the liver to convert its stores of glycogen into glucose, raising blood glucose levels. This can cause a period of high blood sugar following an episode of hypoglycemia. • The Somogyi effect is most likely to occur following an episode of untreated nighttime hypoglycemia, resulting in high blood sugar levels in the morning. • KEY: People who wake up with high blood sugar may need to test their blood glucose levels in the middle of the night (for example, around 3 AM). If their blood sugar level is falling or low at that time, they should speak with their health-care team about increasing their food intake or lowering their insulin dose in the evening. The only way to prevent the Somogyi effect is to avoid developing hypoglycemia in the first place. Lesson 1 Unit 2 – Endocrine Pathophysiology 9 Dawn Phenomenon • The Dawn Phenomenon is the term used to describe an abnormal early-morning increase in blood sugar (glucose) — usually between 5:00 and 9:00a.m. — in people with diabetes mellitus. The main characteristic that sets it apart from a Somogyi effect is that there is NO prior hypoglycemia reaction. • There is research to suggest that it is due to the natural overnight release of hormones — including growth hormones, cortisol, glucagon and epinephrine. Remember that these hormones can increase insulin resistance. • The causes for high morning blood sugar may also include: - Insufficient insulin the night before - Incorrect medication dosages - Eating carbohydrate snacks at bedtime may cause blood sugar to be elevated in the morning. Correction of the Dawn Phenomenon requires an increase in insulin coverage prior to bedtime. When the Dawn Phenomenon occurs in combination with the Somogyi effect, it may produce profound hyperglycemia….a life-threatening situation if not treated immediately. Lesson 1 Unit 2 – Endocrine Pathophysiology 10 Diabetes Mellitus There are two major types of diabetes. The causes and risk factors are different for each type:  Insulin dependent diabetes mellitus (IDDM) Type 1 diabetes can occur at any age, but it is most often diagnosed in children, teens, or young adults. In this disease, the body makes little or no insulin. Daily injections of insulin are needed. The exact cause is unknown.  Non-insulin dependent diabetes mellitus (NIDDM) Type 2 diabetes makes up most diabetes cases. It most often occurs in adulthood. But because of high obesity rates, teens and young adults are now being diagnosed with it. Many people with type 2 diabetes do not know they have it. The distinction between IDDM and NIDDM is clinical: - if insulin therapy is required to prevent ketoacidosis the person has IDDM if insulin therapy is not required to prevent ketoacidosis then the person has NIDDM If the person has NIDDM but insulin is required to maintain acceptable glycemic control then the person has insulin-treated NIDDM Lesson 1 Unit 2 – Endocrine Pathophysiology 11 Type 1A Diabetes (Immune-Mediated) • Type 1A diabetes is a cellular-mediated autoimmune disease characterized by the production of auto-antibodies causing β-cell destruction and subsequent insulin deficiency. Type 1B Diabetes (Idiopathic) • Type 1B diabetes is also referred to as idiopathic diabetes, or diabetes of unknown origin. • This form of type 1 diabetes is not autoimmune in nature, and tests for islet cell antibodies will come up negative. • People with type 1B have an insulin deficiency and can experience ketoacidosis (a high blood sugar emergency), but their need for insulin injections typically comes and goes over time. Patients of African, Hispanic, or Asian descent are more likely to develop type 1B diabetes. Type 2 Diabetes Mellitus • In Type 2 diabetes, insulin is produced but the cells in the body (except for those in the brain) resist its effects especially when the person is obese. • Unlike Type 1 diabetes, Type 2 diabetes develops slowly and gradually. In most cases, insulin-replacement injections are not required. Type 2 diabetes is treated with changing the diet, controlling the weight and taking medications (hypoglycemics) to control the amount of glucose in the body. MODY (maturity-onset diabetes of the young) • Maturity onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes caused by mutations in a sex-dependent (autosomal dominant) gene disrupting insulin production. • MODY is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (especially Type 1 and Type 2). MODY involves more complex combinations of causes involving multiple genes (polygenic) and environmental factors. • Most commonly MODY acts like a very mild version of Type 1 diabetes with continued partial insulin production and normal insulin sensitivity. MODY is not type 2 diabetes in a young person. Lesson 1 Unit 2 – Endocrine Pathophysiology • 12 There are two general types of clinical presentation for MODY: 1. Some forms of MODY produce significant hyperglycemia and the typical signs and symptoms of diabetes: increased thirst and urination (polydipsia and polyuria). 2. Many people with MODY have no signs or symptoms and are diagnosed by either accident, when a high glucose is discovered during testing for other reasons, or screening of relatives of a person discovered to have diabetes. Discovery of mild hyperglycemia can be during a routine glucose tolerance test (GTT) for pregnancy While the goals of diabetes management are the same no matter what type of diabetes, there are two primary advantages of confirming a diagnosis of MODY. Firstly, insulin may not be necessary and it may be possible to switch a person from insulin injections to oral agents without loss of glycemic control (keeping blood sugars at a more constant level rather than seeing valleys and peaks). Secondly, it may prompt screening of relatives and so help identify other cases in family members. Unfortunately, chronic hyperglycemia of any cause can eventually cause blood vessel damage and the microvascular complications of diabetes. The treatment goals for people with MODY include: keeping the blood sugars as close to normal as possible "good glycemic control” and minimizing other vascular risk factors. Diabetic Ketoacidosis People with Type 1 Diabetes are more prone than people with Type 2 diabetes to develop a condition called diabetic ketoacidosis. Ketosis is the abnormal buildup of substances known as ketones. Ketones are caused by the breakdown of too many fats in the event of starvation or as a result of one of the complications associated with Type 1 diabetes. Ketosis and ketoacidosis both involve the buildup of ketones; however ketosis does not involve increased acid levels like what is seen in ketoacidosis. Lesson 1 Unit 2 – Endocrine Pathophysiology Hyperosmolar Hyperglycemic State (HHS) • Hyperosmolar coma occurs because endogenous insulin suppresses ketone formation and thus prevents ketoacidosis • Hyperglycemia may go untreated for a time and result in persistent glycosuria with osmotic diuresis • Dehydration develops with high osmolality and hemoconcentration of erythrocytes, proteins, and creatinine 13