Endocrine system

What is a complication of Addison disease or other adrenal cortical insufficiencies?

Acute adrenal crisis is a life-threatening condition that occurs when there is not enough cortisol. Adrenal crisis can occur gradually or suddenly from - adrenal gland damage due to Addison disease, other adrenal gland diseases, or surgery pituitary injury without ability to release ACTH adrenal insufficiency not properly treated sudden discontinuation of long-term glucocorticoid medicines extreme dehydration infection or other physical stress. In adrenal crisis, destruction of the adrenal cortex leads to a rapid decline in the steroid hormones cortisol and aldosterone. This directly affects the liver, stomach, and kidneys. The flowchart below illustrates what happens in an adrenal crisis. Treatment includes: extracellular fluid restoration - 0.9% saline and 5% dextrose IV oral glucocorticosteroid replacement therapy with the addition of fludrocortisone as amounts of hydrocortisone are decreased - close monitoring of glucocorticoid and mineralocorticoid replacement therapy management of the underlying condition - e.g., infection with a broad-spectrum antibiotic.

What are the adrenal cortical hormones?

Adrenal androgens as DHEA and DHEAS contribute to the pubertal growth of pubic and axillary hair in women and regulation of steroid hormones in pregnant women and the fetal-placental unit. Mineralocorticoid hormones regulate potassium and sodium levels as well as water balance. We'll discuss the role of aldosterone and the renin-angiotensin mechanism in the next module. Cortisol, or the glucocorticoid hormones, are regulated by the negative feedback mechanism of the HPA system. The glucocorticoids are essential for survival by regulating metabolic functions of the body and controlling the inflammatory response. Cortisol, along with other glucocorticoids, stimulate gluconeogenesis by the liver by causing body proteins to be broken down. The resulting amino acids are transported to the liver to produce glucose. It also promotes mobilization of fatty acids from adipose tissue causing conversion of cell metabolism from the use of glucose to the use of fatty acids for energy (this causes blood glucose level to increase, which is significant in those with prediabetes or diabetes mellitus). Large amounts of cortisol are necessary for effective anti-inflammatory action. Administration of synthetic glucocorticoids blocks the early stages of the inflammatory process by inhibiting prostaglandin synthesis and reducing humoral and cell-mediated immunity. Capillary permeability is decreased and inflammatory mediators are blocked. Review Table 41-4 "Actions of Cortisol" in your text to identify the major influences and effects on the body. Long-term therapy with glucocorticoids causes adrenal insufficiency when the drugs are discontinued. This results because the HPA system atrophies due to chronic suppression. Even when given for short periods of time, glucocorticoids must be tapered and not abruptly discontinued. Recovery to normal adrenal function can take a year or more when there has been chronic HPA system suppression.

What is the action of these hormones in maintaining glucose homeostasis? glucagon - travels to the liver and increases blood glucose amylin - inhibits gastric emptying and glucagon secretion somatostatin - inhibits release of inslin and glucoagon gut-derived hormones - increase insulin release following a meal epinephrine - causes glycogenolysis, which results in large amounts of glucose being released into the blood growth hormone - increases cellular protein synthesis, mobilizes fatty acids from adipose tissue, antagonizes rising blood glucose levels adrenal cortical hormones - stimulate gluconeogenesis and decrease tissue use of glucose

Anabolic reactions release energy. True or False? FALSE Rationale: Anabolic reactions use energy to build/produce/synthesize (like building proteins from amino acids). Catabolic reactions break down substances, releasing energy in the process (like digestion). All cells can use fatty acids interchangeably with glucose for energy. True or False? FALSERationale: The only cells that can use fatty acids interchangeably are the brain, nervous system, and erythrocytes. Insulin is produced by the pancreatic beta cells in the islets of Langerhans. True or False? TRUE Rationale: The alpha cells in the islets of Langerhans produce glucagon. Glucagon secretion is stimulated by ingestion of protein, by low blood glucose (hypoglycemia), and by exercise. It is inhibited by the ingestion of carbohydrates, an effect that may be mediated by an increase in blood glucose concentrations and insulin secretion from the beta cells of the islets of Langerhans. ____ lowers the blood glucose concentration by facilitating the movement of glucose into body tissues. Insulin Glucagon, a polypeptide molecule produced by the ____ cells of the islets of Langerhans, maintains blood glucose between meals and during periods of fasting. alpha

What are the thyroid disorders?

As we study disorders of thyroid function, keep in mind the "Manifestations of Hypothyroid and Hyperthyroid States" (Table 41.3 in your text). Thyroid disorders can result from a congenital defect due to an anomaly in prenatal development -- or, a thyroid disorder may be acquired later in life due to a primary disease of the thyroid gland or secondary to disorders of the hypothalamus or pituitary gland.

CARDIORESPIRATORY FUNCTION GASTROINTESTINAL FUNCTION

CARDIORESPIRATORY FUNCTION Cardiorespiratory function rises with increased metabolism - increased oxygen consumption and production of metabolic end productsvasodilation increased blood flow to the skin to dissipate body heat increased blood volume, cardiac output, and ventilation to maintain blood flow and oxygen deliveryheart rate and cardiac contractility increase GASTROINTESTINAL FUNCTION Thyroid hormone increases gastrointestinal function - increased motility and production of secretionscausing diarrhea increased appetite and food consumptionweight loss from increased use of calories

What is primary adrenal cortical insufficiency?

Clinical manifestations result from mineralcorticoid deficiency causing increased urinary losses of sodium, chloride, and water, along with decreased excretion of potassium: hyponatremia loss of extracellular fluid decreased cardiac output hyperkalemia orthostatic hypotension dehydration weakness and fatigue. Glucocorticoid deficiency with poor tolerance to stress results in: hypoglycemia lethargy and weakness fever GI symptoms - anorexia, nausea, vomiting, weight loss. Elevated ACTH levels cause hyperpigmentation: bronzed or suntanned skin darkened creases and pressure points bluish-black gums and oral mucosa. Laboratory diagnostic tests include electrolytes (increased potassium and low sodium), orthostatic hypotension (blood pressure drop upon standing or changing position), low cortisol level, low pH, normal testosterone and estrogen levels, but low DHEA, and high eosinophil count. Additional tests include abdominal x-ray or CT scan and ACTH stimulation test. Treatment involves lifelong replacement of corticosteroids and mineralocorticoids. addisons disease

disorders of growth hormone e

Constitutional tall stature results when a child, who is taller than other children of similar age and gender, grows at a rate that is within a normal range for bone age - for example, a child with exceptionally tall parents. Marfan syndrome is an autosomal dominant genetic disorder involving a mutation in the gene that makes fibrillin causing abnormal connective tissue. While there are variances, the person tends to be tall and thin with long arms, legs, fingers, and toes, flexible joints, and scoliosis. Other areas affected may include the heart, aorta, lungs, eyes, bones, and spinal cord. XYY syndrome is a genetic disorder in which the male has an extra Y chromosome with clinical manifestations that may include being taller than average and/or having acne or learning disabilities. Exceptionally tall children can be treated with sex hormones that begins 3-4 years before epiphyseal fusion - estrogen for girls and testosterone for boys to cause early epiphyseal closure. Gigantism results from excess growth hormone occurring before puberty and the closure of epiphyseal end plates of the long bones. Somatotrope adenomas produce an excessive secretion of GH causing high levels of IGF-1 that produce increased skeletal growth. Early recognition and treatment of the adenoma is the intervention of choice for this condition. Precocious puberty may result from a benign or malignant tumor of the CNS that affects the inhibitory influences on the hypothalamic-pituitary-gonadal axis. Individuals with precocious puberty are tall for their age as children but short as adults because of epiphyseal closure due to the early effects of increased sex hormones. These children develop secondary sexual characteristics and fertility well before the normal age for puberty. Acromegaly occurs in adults (average 40-45 years of age at diagnosis) after the epiphyses of the long bones have fused so that there is an exaggerated growth at the ends of extremities - fingers, hands, toes. Here is what you need to know about ACROMEGALY:

What is hypercortisolism?

Cushing disease is caused by a tumor of the pituitary gland causing excessive production of ACTH. Cushing syndrome is the manifestations of hypercortisolism due to any cause, including pituitary tumor causing excessive ACTH production and - benign or malignant adrenal tumor non-pituitary ACTH-secreting tumor - e.g. small cell carcinoma of the lung that secretes ACTH or CRH long-term therapy with glucocorticoids - iatrogenic Cushing syndrome. The clinical manifestations appear in the image below: Diagnosis is made by finding the cause of cortisol hypersecretion: 24-hour excretion of cortisol in urine late night serum or salivary cortisol levels (11 pm-midnight) overnight dexamethasone suppression test. Treatment is aimed at lowering the high level of cortisol by treating the causative factor: reducing corticosteroid use - taper to reduce the required dosage surgery - removal of the pituitary tumor via transsphenoidal removal or hemihypophysectomy (remove only the tumor to preserve pituitary gland) pituitary radiation therapy unilateral or bilateral adrenalectomy (for adrenal adenoma) removal of ACTH-producing ectopic tumors pharmacologic agents that block steroid synthesis.

What is the impact of the counterregulatory hormones? Somogyi Effect

Definition: Cycle of insulin-induced posthypoglycemic episodes; more often occurring in Type 1 Pathogenesis: compensatory increase in blood levels of catecholamines, glucagon, cortisol and growth hormone à blood glucose elevation and insulin resistance Treatment: redistribution of dietary carbohydrates and alteration of insulin dose or timing of administration Dawn Phenomenon Definition: Increased levels of FPG and/or insulin requirements between 5-9 am without preceding hypoglycemia Occurs in type 1 or type 2 Alteration of normal circadian rhythm changes for glucose tolerance resulting in mild hyperglycemia Complication When the Dawn Phenomenon is combined with the Somogyi Effect, profound hyperglycemia results

What are the long-term, chronic complications of diabetes mellitus?

Degenerative changes occur in many tissues with both types of diabetes, particularly when blood glucose levels are poorly controlled. The insulin deficit and glucose excess cause a number of alterations in metabolic pathways involving, carbohydrates, lipids, and proteins. Pathogenesis of chronic complications... The following theories describe how intracellular hyperglycemia disturbs metabolic pathways. Polyol Pathway Intracellular mechanisms responsible for changing number of hydroxyl units on a glucose molecule Glucose readily transformed to sorbitol, but conversion to fructose limited Excess intracellular sorbitol may alter cell function in eye lens, kidneys, nerves, and blood vessels Formation of Advanced Glycation End Products (AGE) Increased production due to increased intracellular glucose - Abnormal glycoproteins produce structural defects in the basement membrane of the microcirculation (smaller blood vessels and capillaries) resulting in complications of the eye, kidneys, and vasculature Protein Kinase C (PKC) DAG (diacyglycerol) and PKC are critical intracellular signaling molecules regulating vascular function - DM increases levels of DAG and PKC causing vascular permeability, vasodilator release, endothelial activation, & growth factor signaling Activation of PKC in blood vessels of the retina, kidney, and nerves results in vascular damage.

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Describe the action for each of the following oral antidiabetic agents: sulfonylureas, meglitinides, biguanides, glucosidase inhibitors, thiazolidinediones, incretin-based agents Sulfonylureas—act on pancreatic beta cells to stimulate insulin secretion Meglitinides—act on pancreatic beta cells to stimulate insulin secretion Biguanides—inhibit hepatic glucose production; increase sensitivity of peripheral tissues to action of insulin Glucosidase inhibitors—block action of intestinal brush border enzymes that break down complex CHOs Thiazolidinediones—increase insulin sensitivity Incretin-based agents—potentiate glucose-mediated insulin release; slow gastric emptying; decrease appetite Describe the action for each of the following types of insulin: short-acting insulin, rapid-acting insulin, intermediate to long-acting insulin. Short-acting insulin—onset within 30 minutes; duration 5 to 8 hours Rapid-acting insulin—administered immediately before a meal Intermediate-acting to long-acting insulin—slower onset of action with a longer duration of action; requires supplementation with rapid- or short-acting insulin

What is the definition of diabetes mellitus?

Diabetes mellitus is a disorder of carbohydrate, protein and fat metabolism caused by a relative deficit of insulin secretion from the beta cells in the islets of Langerhans or by the lack of response by cells to insulin (insulin resistance). Insulin is an anabolic hormone, meaning it builds up complex substances from simple molecules. Deficient insulin results in abnormal carbohydrate, protein, and fat metabolism because the transport of glucose and amino acids into cells is impaired - as well as the synthesis of protein and glycogen. In turn, these metabolic abnormalities affect lipid metabolism. Many tissues and organs in the body are adversely affected by diabetes.

What are 3 acute complications of diabetes? These are the 3 acute complications:

Diabetic ketoacidosis (DKA) — acute, life-threatening event in presence of severe stress (trauma, sepsis); characterized by hyperglycemia, ketosis, metabolic acidosis Hyperosmolar hyperglycemic state (HHS) — hyperglycemia, hyperosmolarity, dehydration, absence of ketoacidosis, sensorium depression Hypoglycemia (insulin reaction) — rapid onset and progression of symptoms relative to excess of insulin in blood characterized by below-normal blood glucose level

What is diabetic nephropathy?

Diabetic nephropathy is a combination of lesions occurring concurrently in the diabetic kidney that leads to chronic kidney disease (CKD). Risk factors for nephropathy include genetic/familial predisposition (Native Americans, African Americans, Hispanic), elevated blood pressure, poor glycemic control, smoking, hyperlipidemia, and microalbuminuria. Commonly kidney lesions occur in the glomeruli with capillary basement membrane thickening, diffuse glomerulosclerosis, and nodular glomerulosclerosis. In nodular glomerulosclerosis, there is impaired blood flow causing progressive loss of glomerular function, and eventually, kidney failure. The signs of impaired kidney function are hyperalbuminuria, hypoalbuminemia, and edema. Kidney enlargement, nephron hypertrophy, and hyperfiltration are the early signs of diabetes indicating the excessive renal workload in reabsorbing excess glucose. Microalbuminuria is one of the first signs of renal complications. Microalbuminuria is defined as urine protein loss between 30-300 mg/day in a 24-hr urine collection or albumin-to-creatinine ratio between 30-300 µ/mg from a spot urine collection. Prevention and early management are - glycemic control blood pressure control (<130/80 mmHg) prevention or reduction of proteinuria involving ACE-inhibitor medication and/or a protein-restricted diet treatment of hyperlipidemia smoking cessation for smokers.

Why is blindness a complication of diabetes?

Diabetic retinopathy is the leading cause of acquired blindness and is characterized by abnormal vascular permeability, microaneurysm formation, neovascularization with associated hemorrhage, scarring, and retinal detachment. Other eye complications include cataracts and glaucoma. Risk factors for diabetic retinopathy are poor glycemic control, elevated blood pressure, and hyperlipidemia. Prevention and early treatment include an annual dilated eye exam with referral to an ophthalmologist for macular edema, moderate to severe non-proliferative retinopathy, or any proliferative retinopathy. Treatment involves destruction of proliferative lesions with laser photocoagulation and use of antagonists to growth factors (vascular endothelial growth factor).

Hyperosmolar Hyperglycemic State

Diagnosis: blood glucose >600 mg/dL, plasma osmolarity >320 mOsm/L, (-)ketoacidosis, dehydration, depression of sensorium; occurs more often in elderly as stroke Pathogenesis: most common in type 2 DM; partial or relative insulin deficiency causing reduction of glucose utilization and hyperglucagonemia with increasing hepatic output à fluid loss & dehydration hyperosmolarity pulls water out of body cells, including brain cells Clinical Manifestations: insidious onset; weakness, dehydration, polyuria, polydipsia, hemiparesis, neurologic signs and symptoms: (+)Babinski reflex, aphasia, muscle fasciculations, hyperthermia, hemianopia, nystagmus, visual hallucinations, seizures, coma Treatment: poor prognosis; medical management of hyperglycemia and dehydration; treatment complication à cerebral edema

Diabetic Ketoacidosis (DKA)

Diagnosis: hyperglycemia — hyperglycemia (>250 mg/dL), low serum bicarbonate, low arterial pH, (+)urine and serum ketones Pathogenesis: Ketosis — rapid breakdown of energy stores from muscle & fat with movement of amino acids to liver for gluconeogenesis & fatty acids converted to ketones; increase glucagon and counterregulatory hormones Metabolic acidosis — excess ketoacids requiring buffering by bicarbonate ions with marked decrease in bicarbonate ions Hyperglycemia — causing osmotic diuresis, dehydration, loss of electrolytesPseudohyponatremia — intracellular-extracellular fluid shift with sodium levels slightly low or near normal Clinical Manifestations: polyuria, polydipsia, nausea, vomiting, marked fatigue, stupor, coma, fruity breath odor, hypotension, tachycardia, Kussmaul respiration Treatment: improve circulatory volume & tissue perfusion, decrease blood glucose, correct acidosis & electrolyte imbalance; treatment complication is cerebral edema

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Diet Therapy is based on maintaining optimum body weight as well as control of blood glucose levels. Recommended diets include: complex carbohydrates (low glycemic index in contrast to simple sugars) adequate protein maintenance of low cholesterol and lipids through controlled intake increased fiber with meals to reduce surges in blood sugar associated with food intake. Food intake has to match available insulin and metabolic needs (including activity level). Exercise A regular moderate exercise program is very beneficial to the diabetic. Exercise can substantially increase uptake of glucose by muscles without an increase of insulin use. It also assists in weight control, reduces stress, and improves cardiovascular fitness. Note that hypoglycemia may develop with exercise, especially strenuous, or prolonged exercise. Increased use of glucose by skeletal muscle, plus the increased absorption of insulin from the injection site, may lower blood glucose levels precipitously. Increasing carbohydrate intake by eating a snack to compensate for exercise can decrease this risk. Oral Medications Antidiabetic agents or oral hypoglycemic drugs are useful in the treatment of Type 2 diabetes when diet and exercise alone are not effective.

What are disorders of growth hormone excess?

Excess growth hormone can affect children (tall stature or gigantism) or adults (acromegaly) and result from genetic or chromosomal disorders (remember Marfan syndrome from Unit 1?), benign somatotrope adenomas, or benign/malignant CNS tumors that activate the hypothalamic-pituitary-gonadal axis.

How is the diagnosis made?

Fasting blood glucose level, the glucose tolerance test, and the glycosylated hemoglobin (HbA1C) test are used to screen people with clinical and subclinical diabetes. At present, a fasting blood sugar >126 mg/dL, taken on more than one occasion, confirms a diagnosis of diabetes. The test for HbA1C is used to monitor long-term control of blood glucose levels. It measures control over an 8-12 week period and is evaluated every 3 months. The goal is keep the person with diabetes to 7% or less (normal is <6%). What are the criteria for diagnosis of diabetes? (See table 41-4 in your text.) Prediabetes (Increased risk): Impaired fasting glucose between 100-125 mg/dL Impaired glucose tolerance between 140-199 mg/dL Diabetes mellitus diagnostic criteria: FPG: >126 mg/dL; or 2-H OGTT: >200 mg/dL; or HbA1C: >6.5%; or Classic symptoms of hyperglycemia or hyperglycemic crisis and a plasma glucose >200 mg/dL. Let's see what you know Can you describe the role of insulin in the metabolism of glucose, fat, and protein? How is insulin related to the manifestations of diabetes? Discuss the diagnostic testing methods for diabetes.

Gestational Diabetes

Gestational diabetes mellitus (GDM) is glucose intolerance developing during pregnancy that is not overt diabetes. If blood glucose is not diagnosed and controlled during pregnancy, the mother and the infant are at risk of death and/or fetal abnormalities. Fetal abnormalities may be macrosomia, hypoglycemia, hypocalcemia, polycythemia, and hyperbilirubinemia. GDM can respond to dietary management, but may require insulin. More recently, certain oral antidiabetic agents have been found to be successful in treating GDM glucose intolerance. Women who develop GDM should be monitored after pregnancy because they are more likely to develop type 2 diabetes within 5-10 years. The children of GDM mothers also are at greater risk for development of diabetes mellitus.

Langerhans:

Glucagon is produced by the alpha cells of travels through the portal vein to the liver causing --Glycogenolysis, andincreases the transport of amino acids to the liver for gluconeogenesis.High concentrations of glucagon activate adipose cell lipase to break down triglycerides into fatty acids (lipolysis), andhigh concentrations of amino acids stimulate glucagon secretion to increase the conversion of amino acids to glucose Somatostatin inhibits the release of insulin and glucagon Insulin is necessary for carbohydrate, fat, and protein metabolism Amylin inhibits gastric emptying and glucagon secretion. In addition, the gut-derived hormones exert the incretin effect - the incretin hormones stimulate insulin secretion after oral intake of carbohydrates. Catecholamines, growth hormone, and glucocorticoids are the backup mechanism to counteract insulin when there is limited glucose available - for example, periods of fasting, exercise, or other occurrences that limit glucose intake or deplete glucose stores. These are the counterregulatory hormones: Epinephrine causes glycogenolysis, which results in large amounts of glucose being released into the blood Growth hormone increases cellular protein synthesis, mobilizes fatty acids from adipose tissue, and antagonizes rising blood glucose levels Adrenal cortical hormones stimulate gluconeogenesis and decrease tissue use of glucose.

What controls the body's fuel supply?

Glucose is the primary fuel source for the brain and nervous system, but other body systems can use fatty acids and ketones, along with glucose, to supply fuel for cellular activity. Glucose is stored in the liver as glycogen or converted to fat. Glycogenolysis is the process of breaking down stored glycogen to release glucose when blood glucose levels fall below normal. The liver also synthesizes glucose from amino acids, glycerol, and lactic acid in a process termed gluconeogenesis. Fat is the most efficient form of fuel storage. Lipases break down triglycerides (this is the form of fat stored in adipose tissue) into fatty acids and glycerol. These products enter the glycolytic pathway with glucose to produce energy. There is an exception - fatty acids are not used by the brain, nervous tissue, or red blood cells for energy; glucose is required by these cells. Protein is an essential nutrient for the formation of our body structures. Most proteins are stored as amino acids; but the excess is converted to fatty acids, ketones, or glucose. When the metabolic needs exceed food intake, the body breaks down proteins in order to use amino acids for gluconeogenesis.

Glucose transporters

Glucose transporters move glucose from the blood into the cell membranes that are usually impermeable to glucose -GLUT-1 is present in all tissues and does not require insulin to transport glucose into the nervous systemGLUT-2 is a major transporter of glucose into beta cells and liver cells when plasma glucose levels are highGLUT-4 insulin-dependent glucose transporter is necessary to transport glucose into skeletal muscles and adipose tissues -- (1) Insulin binds to the insulin receptor on the surface of the cell membrane, causing (2) an intracellular signal to be generated. (3) The GLUT-4 receptor is inserted from its inactive site into the cell membrane, and (4) glucose is transported across the cell membrane.

GOITER

Goiters are an increase in the size of the thyroid gland and are dependent on the extent and duration of thyroid deficiency or excess. Goiters may be diffuse without nodules or diffuse with nodules and arise from compensatory hypertrophy and hyperplasia due to follicular derangement. Interestingly, goiters can increase in size in hypothyroid, hyperthyroid, or euthyroid state. Multinodular goiters are the largest and can compress the esophagus and trachea resulting in choking and inspiratory stridor with the potential to compress the superior vena cava.

What are disorders of growth hormone deficiency?

Growth hormone deficiency in children results in short stature due to many factors (see Chart 41-2) including chromosomal abnormalities (remember Turner syndrome from Unit 1?), growth hormone deficiency, hypothyroidism, and panhypopituitarism. But chronic diseases like diabetes mellitus, chronic kidney disease, and malabsorption syndromes can also result in growth deficiency. Malnutrition, emotional disturbances, and glucocorticoid administration (for treatment of certain diseases or transplants) can also result in short stature. short stature. disease card in ipad GROWTH HORMONE DEFICIENCY IN ADULTS: in ipad disease card

Why do infections develop in diabetics?

Hyperglycemia and glycosuria promote the growth of microorganisms, increase infection severity, and impair neutrophils and immune cells function of adherence, chemotaxis, phagocytosis. As a result, uncontrolled diabetics experience increased incidence of soft tissue infections of extremities, osteomyelitis, urinary tract infection and pyelonephritis, candida infections of skin and mucous membranes, dental caries and periodontal disease, and tuberculosis. The suboptimal response to infection results from vascular disease, neuropathies, hyperglycemia, and altered neutrophil function: Sensory deficit - lack of awareness of minor trauma/injury/ infection especially to lower extremities and feet Vascular disease - impair delivery of blood cells to mount an adequate inflammatory response that promotes healing Neurogenic bladder and nephrotic changes - urinary tract infections and pyelonephritis.

Disorders of Hyperthyroidism

Hyperthyroidism results when tissues are exposed to high levels of circulating thyroid hormone. Most common causes are Graves' disease and diffuse goiter. However, other causes include - multinodular goiter, thyroid adenoma, thyroiditis, and excess of iodine-containing agents.

What causes hypopituitarism?

Hypopituitarism results when there is decreased secretion of the pituitary hormones resulting in decreased stimulation of secondary organs that depend on the pituitary trophic hormones. Undersecretion of the pituitary may affect just one subset of pituitary cells (e.g., somatotropin) or all (panhypopituitarism). Causes may be congenital abnormality, destruction of the pituitary, or secondary due to a deficiency of hypothalamic hormones. Pituitary reserves last 10-20 years, so anterior pituitary hormone loss is gradual and progressive with depletion occurring first with the loss of GH, LH, and FSH secretion, followed by TSH, then ACTH, and lastly, prolactin.

What controls the body's fuel supply?

If you said - the liver - you are correct! It is the liver in conjunction with insulin and other hormones that control storage and mobilization of our fuel supply. Certain hormones control the nutrients we ingest - that is, carbohydrate (glucose), fat, and protein. Metabolism is comprised of anabolism and catabolism. So - anabolism is the process of building up complex chemical compounds from smaller simpler compounds - for example, proteins from amino acids. Catabolism is the process by which complex substances are converted into simpler compounds - for example, glycogen is degraded into carbon dioxide and water, and as a result - energy is released. As you can see - metabolism is a 2-way process - see these examples: glucose < > glycogen free fatty acids + glycerol < > triglycerides amino acids < > proteins.

What is the most common complication of diabetes?

If you said diabetic foot ulcers, you are correct. The risk factors for these ulcers are the distal symmetric neuropathy and foot deformities that contribute to trauma caused by poorly fitting shoes, improper weight bearing, hard objects in shoes, and infections (e.g., athlete's foot). The trauma sites are the back of heel, plantar metatarsal, and great toe. Peripheral vascular disease contributes to poor healing of injury sites with skin breakdown and ulceration Prevention and early management include: annual assessment (or more frequently) of neurologic function including Semmes-Weinstein monofilament or vibratory sensation correctly fitted shoe and warm foot coverings daily foot inspection for blisters, sores, fungal infection podiatric management of thickened, deformed toenails smoking cessation, if smoker. Treatment of foot ulcers that are resistant to standard management involves the application of topical becaplermin, a recombinant human platelet-derived growth factor.

What is the pathophysiology and the clinical manifestations of DM?

Insulin deficit leads to the following sequence of events: Insulin deficit results in decreased transportation and use of glucose in many cells of the body causing blood glucose levels to rise resulting in hyperglycemia. Glucose in the filtrate exceeds the capacity of the renal tubular transport limits and reabsorption is impaired causing glucosuria. Glucose in the urine exerts osmotic pressure in the filtrate which causes a large volume of urine to be excreted, or polyuria. Polyuria causes the loss of fluid and electrolytes (sodium and potassium) from body tissues, which results in dehydration - this causes thirst, or polydipsia. Nutrients fail to enter cells and appetite is increased resulting in increased hunger, or polyphagia. Typically, the three Ps - polyuria, polydipsia, and polyphagia - signal the onset of diabetes.

What is the effect of insulin on lowering blood glucose levels?

Insulin is necessary to transport glucose into the cells to be used as a source of energy and is necessary for carbohydrate, fat, and protein metabolism. Active insulin is composed of two polypeptide chains - an A chain and B chain - and is formed in the beta cells from a larger molecule, called proinsulin. Proinsulin is comprised of the A chain and the B chain linked by C-peptide, which is a biologically inactive connecting peptide. Enzymes in the beta cell spit C-peptide from the A and B chains forming active insulin that is packaged with C-peptide into secretory granules that are released from the beta cells Active insulin enters the portal circulation in response to rising blood glucose levels and travels to the liver where glucose is stored as glycogen Insulin in the circulatory system binds to membrane receptors that have 2 alpha subunits extending outside the cell membrane and 2 beta subunits inside the cell - these activate the kinase enzyme The kinase enzyme causes autophosphorylation of the beta subunit, which then activates some enzymes and inactivates others resulting in the intracellular action of insulin on glucose, fat and protein metabolism

Insulin Replacement

Insulin must be injected subcutaneously because it is a protein that is destroyed in the digestive tract when taken orally. Continuous infusions via a small pump are favored by some diabetics and can provide better control of glucose levels. The primary form of insulin used now is a biosynthetic form of insulin - identical to human insulin that is synthesized by bacteria using recombinant DNA techniques. Insulin is standardized in units for subcutaneous administration and is produced in these forms: rapid-onset, short-acting (regular) insulin, intermediate-acting insulin, and slow-onset-long-acting insulin.

The type of insulin used and its effective period can be important factors in predicting periods of potential hypoglycemia in individual patients, and food intake can be timed to coincide with peak insulin levels in order to avoid hypoglycemia. Injection sites must be rotated to minimize skin damage.

Insulin types may be mixed for administration, and several injections may be required in 1 day. Insulin dosage may also require adjustment under special circumstances - like infection with high fever or vomiting, or at the time of surgery. Continuous control of blood glucose levels minimizes the risk of potential complications. Improved self-monitoring devices are helpful. Small, computerized recording and data bank devices have improved the compliance of young adults. Two types of intensive treatment regimens provide a more normal pattern of insulin secretion by the body: Multiple daily injections (MDIs) - basal insulin requirements met by intermediate- or long-acting insulin given once or twice a day; before meals rapid- or short-acting insulin boluses are given Continuous subcutaneous insulin infusion (CSII) - an insulin pump provides continuous infusion of subcutaneous insulin at preset intervals; before meals a bolus of insulin is delivered by pressing a button. Hyperglycemia and ketotic episodes are complications due to pump failure, clogging of catheter, and infections.

So - how does insulin lower blood glucose levels?

It promotes glucose uptake by target cells and provides for glucose storage as glycogen --Oral glucose increases blood plasma glucose levels causing the beta cells to secrete insulin, where it enters the portal circulation and is stored as glycogen in the liverThe remaining glucose enters the circulatory system and binds to membrane receptors to be transported into target cells. It prevents fat and glycogen breakdown --Insulin increases the transport of glucose into fat cells and facilitates triglyceride synthesis (3 fatty acids linked by a glycerol molecule) for storage in adipose tissues, andinhibits the intracellular break down of stored triglycerides. It inhibits gluconeogenesis and increases protein synthesis --Insulin transports amino acids into the body cells, andprevents the use of amino acids for glucose synthesis.

What are the macrovascular long-term complications?

Macrovascular complications of diabetes are atherosclerotic coronary artery disease, cerebrovascular disease, and peripheral vascular disease. The risk factors are obesity, hypertension, hyperglycemia, hyperinsulinemia, hyperlipidemia, altered platelet function, endothelial dysfunction, systemic inflammation (elevated C-reactive protein), and elevated fibrinogen levels. Prevention and early management involves aggressive management of cardiovascular risk factors with diet, antidiabetes agents, antihypertensives, lipid lowering agents, and antiplatelet agents.

How is diabetes managed?

Maintenance of normal blood glucose levels is important to prevent short-term complications and delay long-term complications of diabetes mellitus. Glucose intake must be balanced with use with the goal of normalizing blood glucose to prevent short-term complications and prevent or delay long-term complications Treatment measures depend on the severity of the insulin deficit and may change over time. Here are the 3 levels of control that may be used: diet and exercise oral medication to increase insulin secretion or reduce insulin resistance insulin replacement.

What are the complications of diabetes mellitus?

Many factors can lead to fluctuations in serum glucose levels and subsequent changes in cell metabolism throughout the body. These changes can result from variations in diet or physical activity, the presence or infections, or alcohol use. Complications may be acute or chronic. Long-term complications like vascular disease result from generative changes in the the tissues. Stable blood glucose levels reduce the risk of complications.

METABOLIC RATE

Metabolic rate elevation increases the metabolism of body tissues by increasing glucose, fat, and protein use rate - increased absorption of glucose from GI tract increased lipid mobilization from adipose tissues and catabolism of cholesterol by the liverincreasing blood cholesterol increased break down of muscle proteins to be used as fuel accelerated use of vitaminsexcess can cause vitamin deficiency

Hypoglycemia - Insulin Shock

More often occurs in Type 1; however, certain oral antidiabetes agents can cause in Type 2; elderly or individuals with "hypoglycemia unawareness" Precipitating factors: insulin dose error/failure to decrease insulin dosage after stress, failure to eat, increased exercise, medication changes, change in insulin injection site; excessive alcohol intake Clinical manifestations: rapid onset and symptom progression Altered cerebral function — headache, difficulty in problem-solving, altered behavior/mental confusion, coma, seizures Activation of autonomic nervous system — hunger, anxiety, tachycardia, sweating, cool/clammy skin (vasoconstriction of skin vessels) Treatment: immediate administration 15-20 g glucose (monosaccharide) in concentrated carbohydrate source; if unconscious, glucagon IM or SQ or IV glucose

Mechanisms that result in hyperglycemia and/or insulin resistance:

Skeletal musclesinsulin resistance causes decreased uptake of glucosediminished glucose clearance after a mealincrease in postprandial blood glucose levels Liverinsulin resistance causes impaired suppression of glucose productionoverproduction of glucose even in presence of fasting hyperinsulinemia (high levels of insulin in blood even though there has been no food intake) Adipose tissuevisceral obesity is accompanied by increase in postprandial free fatty acid (FFA) concentration and elevated triglyceridesexcessive and chronic elevation of FFAs cause pancreatic beta cell dysfunctionin peripheral tissues FFAs inhibit glucose uptake and glycogen storageaccumulation of FFA and triglycerides reduce hepatic insulin sensitivity resulting in increased hepatic glucose production and hyperglycemia (especially when fasting)decreased production of adiponectin and increased release of factors that result in poor glucose and lipid metabolism, inflammation, and thrombosis.Adiponectin increases use of FFA as a fuel source and has antidiabetes, anti-inflammatory, and antiatherogenic effects (Later, we'll discuss how this problem leads to long-term complications in diabetes).

What are the glucose-regulating hormones? In the previous lesson, we studied the exocrine pancreas. Now, let's take a look at the endocrine pancreas - this is where hormonal control of blood glucose resides. There are 2 major tissue types that comprise the pancreas - the acini and the islets of Langerhans.

The acini secrete the pancreatic digestive juices into the first part of the small intestines, or duodenum, to continue the break down of partially-digested food - called chyme. The islets of Langerhans secrete hormones into the blood. Each of the islets has alpha cells that secrete glucagon and delta cells that secrete somatostatin. In addition, the islets contain beta cells that secrete insulin and amylin.

What is the primary cause of hyperpituitarism?

The main cause of hyperpituitarism in adults is a benign tumor arising from the anterior pituitary, called pituitary adenoma. These tumors may be very small (microadenomas) and are found incidentally. Macroadenomas can erode into the sella turcica and impinge on nearby cranial structures. Categories of pituitary adenomas are functional and nonfunctional. Clinical manifestations result from both functional tumors and the spread of the tumor causing endocrine abnormalities related to hypersecretion.

What are the adrenal cortical hormones?

The adrenal glands rest on top of the kidneys. About 90% of the gland is made up of the cortex and the remainder is the medulla. The adrenal cortex produces more than 30 hormones - we will discuss the adrenal androgens, the mineralcorticoids and the glucocorticoids. Adrenal androgens and glucocorticoids are controlled by ACTH, which is secreted by the anterior pituitary. Physiological, psychological or environmental factors - like stress, infection, pain, hypoglycemia, sleep, hemorrhage, and trauma - trigger the cortisol releasing hormone (CRH) from the hypothalamus. CRH causes the anterior pituitary to secrete ACTH, which in turn, causes the release of cortisol to the target tissues. The simple feedback loop controls secretion of ACTH and the complex feedback loop controls CRH. Aldosterone and androgens bind to albumin, and cortisol binds to corticosteroid-binding globulin for transport in the circulatory system. Metabolism of these hormones occurs in the liver where they are made water soluble (conjugated) to be excreted in urine or bile.

A brief note about endocrine function and disorders in general...

The endocrine system along with the nervous system regulates and integrates functions of many body cells and organs. So - what causes endocrine malfunction? Typically, these causes include - impaired or uncontrolled synthesis or release of hormones altered interaction between hormones and target cells/tissues abnormal response of target cells/tissues to the hormone. The effects of altered endocrine function are either hypofunction or hyperfunction.

How is adrenal function measured?

The following are diagnostic tests to evaluate adrenal cortical function and the HPA system: Immunoassays of cortisol, aldosterone, ACTH - determination of levels in the body 24-hour urine - measures excretion of metabolic end products of adrenal hormones Overnight dexamethasone suppression test - diagnose Cushing syndrome and causelow-dose (1 mg of dexamethasone) test - diagnostic of Cushing when the cortisol level dropshigh-dose (8 mg of dexamethasone) test - determine if Cushing syndrome is caused by tumor of pituitary gland. ACTH stimulation test - measures how well adrenal glands respond to adrenocorticotropic hormone (ACTH); test for adrenal insufficiencyBaseline blood is drawn to determine cortisol levelsACTH injection is given30-60 minutes later blood is drawn to determine if cortisol levels have increased Insulin-induced hypoglycemia test - determine how hypothalamus, pituitary and adrenal glands respond to stressBaseline blood draw of glucose and cortisol levelsInjection of fasting-acting insulinBlood glucose and cortisol are measured at 30, 45, and 90 minutes after the insulin injection (the normal response is for blood glucose levels to fall and cortisol levels rise).

What is the role of somatotropin?

The growth hormone (somatotropin) is stimulated when the hypothalamus secretes the growth hormone-releasing hormone (GHRH), which in turn, stimulates the anterior pituitary to secrete the growth hormone. Somatostatin inhibits the anterior pituitary growth hormone secretion. Growth hormone secretion is stimulated by hypoglycemia, fasting, starvation, and stress. While it is inhibited by increased glucose levels, free fatty acid release, obesity, and cortisol. Review the growth hormone function as demonstrated in Figure 32-1 from the text (IGF-1 = insulin-like growth factor-1 and FFA = free fatty acid).

How is thyroid hormone secretion regulated?

The hypothalamic-pituitary-thyroid axis regulates the secretion of the thyroid hormones as follows: Thyroid-releasing hormone (TRH) is produced by the hypothalamus in response to disturbance in homeostasis triiodothyronine (T3) and thyroxine (T4) decreased concentration in bloodlow body temperature (cold exposure) TRH controls the release of thyroid-stimulating hormone (TSH) from the anterior pituitary glandemotional reactions indirectly affect the output of TRH and TSH TSH increases the activity of the thyroidincreases thyroglobulin breakdown and release of thyroid hormones from follicles into the bloodstreamincreases activity of the iodide pump and iodination of tyrosine to increase production of thyroid hormones Increased levels of thyroid hormones inhibit TRH or TSH

How is the system regulated?

The hypothalamus exerts hormonal control at the anterior pituitary gland by releasing or inhibiting hormones. Hypothalamic hormones stimulate the anterior pituitary gland to release the tropic (gland-stimulating) hormones. The secretion of tropic hormones stimulates their respective target glands, such as the thyroid gland, the adrenal cortex, and the gonads. Hypothalamic hormones also control the release of effector hormones from the pituitary gland. Examples are growth hormone (GH) and prolactin. A negative feedback system regulates the endocrine system by inhibiting hormone overproduction. The system may be simple or complex. The diagram below demonstrates the negative feedback loop. Simple feedback occurs when the level of one substance regulates secretion of hormones Complex feedback occurs when the hypothalamus receives feedback from target glands through an axis established between the hypothalamus, pituitary gland, and target organ.

pituitary tumors

The most frequently-occurring pituitary tumors are lactotrophic adenomas resulting in hyperprolactinemia that inhibits secretion of luteinizing hormone (LH). So - no surprise - signs and symptoms are most often recognized in women of reproductive age and include - amenorrhea, galactorrhea, and infertility. Manifestations in men are vaguer - erectile dysfunction and loss of libido. As the tumor expands, it erodes into the sella turcica and can compress the optic chiasm causing visual field abnormalities with blurred or double vision. Other cranial nerve abnormalities may be a burning or prickling sensation (paresthesia) on one side of the face. Intracranial pressure increase can cause headache, nausea, and vomiting. If the tumor extends into the base of the brain, seizures and/or obstructive hydrocephalus may result.

What are the manifestations of hypothalamic-pituitary disorders?

These include -- Hyperpituitarismpituitary adenoma in adult Hypopituitarismhypothalamic tumor (craniopharyngioma) in childshort staturedelayed puberty Localized mass effect causing compression of optic chiasm or basal portion of brainheadachevisual lossneurologic symptoms

How does diabetic neuropathy occur? Pathology

Thickening of wall of nutrient vessels that supply the nerve result in vessel ischemia Segmental demyelination affecting Schwann cells causes slowing of nerve conduction Somatic neuropathy Distal, symmetric polyneuropathy results in diminished perception of vibration, pain, and temperature that occurs primarily in lower extremities. The resulting symptomatology is hypersensitivity to touch and/or severe burning pain in extremities. This increases the risk of falls due to loss of feeling, touch, and position sense. Because of decreased sensation, the individual is at risk for serious burns. Foot trauma and ulcers can occur because of clawing of foot and submetatarsal fat pad formation with anterior displacement. Autonomic neuropathy Disorders of vasomotor function include decreased cardiac responses, inability to empty bladder, abnormality in GI motility, and sexual dysfunction. The clinical manifestations of autonomic neuropathy include: Dizziness and syncope d/t orthostatic (postural) hypotension Urine retention with urinary stasis, bladder infections & increased risk of renal complications Gastroparesis (delayed emptying of stomach) — epigastric discomfort, nausea, postprandial vomiting, bloating, early satiety Diabetic diarrhea with fecal incontinence Erectile dysfunction.

Other Specific Types of DM

This category of DM include types of diabetes that are secondary to other conditions or syndromes as a result of pancreatic disease, excision of pancreatic tissue, occurring in conjunction with other endocrine diseases, or specific gene defects affecting beta cell function (like maturity-onset diabetes of the young (MODY) and cystic fibrosis-related diabetes (CFRD)). In addition, drugs can also elevate blood glucose; but these drug-related increases are generally reversed after the drug is discontinued. Thiazide and loop diuretics, glucocorticoids, oral contraceptives, antipsychotic agents, and total parenteral nutrition - all can contribute to hyperglycemia.

What is congenital adrenal hyperplasia?

This is the name given to a group of inherited disorders of the adrenal gland. Individuals with congenital adrenal hyperplasia (CAH) lack an enzyme needed by the adrenals to make hormones. At the same time, the body produces more androgen causing male characteristics to appear early, or inappropriately. This condition can affect both boys and girls - about 1 in 10,000 to 18,000 children are born with CAH. Clinical manifestations vary, depending on the type of CAH and the age when the disorder is diagnosed. Some may have little if any changes at birth and not be diagnosed until adolescence. Children with more severe forms have clinical manifestations that develop within 2-3 weeks after birth including poor feeding or vomiting, dehydration, electrolyte changes, and abnormal heart rhythm. Girls with severe forms have abnormal genitals at birth, but have normal female reproductive organs - some later changes may include:abnormal menstrual periods or failure to menstruateearly appearance of pubic or axillary hairexcessive hair growth or facial hair Boys appear normal at birth, even with a severe form, though they may enter puberty early, with some changes including:deepening voiceearly appearance of pubic or axillary hairenlarged penis but normal testeswell-developed muscles. Common blood tests include serum electrolytes, aldosterone, renin, and cortisol. X-ray of the left hand and wrist may show the child's bones appear to be older than the child's actual age. Genetic tests can diagnose or confirm the disorder but are rarely necessary. The treatment goal is to return hormone levels to normal or near normal.

NEUROMUSCULAR EFFECTS

Thyroid hormone elevations increase neural control of muscle function and tone - fine muscle tremor due to increased sensitivity of neural synapses in the spinal cord enhanced celebration in infantnervousness, anxietydifficulty sleeping over-activity of autonomic nervous systemtachycardia, palpitationssweatingtremor, restlessness, anxietydiarrhea

What are the actions of thyroid hormone?

Triiodothyronine (T3) is the primary mediator of metabolism and protein synthesis - as you will see, it affects most of the major body organs. The following identifies the effects on body organs due to increased release of thyroid hormones (hyperthyroidism). Consider how hypothyroidism would generate the opposite effect.

A rare complication resulting from hemorrhage into the pituitary adenoma causing rapid enlargement is ____. pituitary apoplexy What are the clinical manifestations of this complication? acute nerve palsies, severe headache, systemic symptoms related to ACTH deficiency Which hormone(s) is/are secreted by the anterior pituitary to stimulate the ovaries and testes? A. GH, B. FSH and LH, C TSH, or D. ACTH and GH Rationale: Gonads are sex organs (ovaries and testes). These organs are stimulated by follicle-stimulating hormone (FSH) and luteinizing hormone (LH). the answer is BBBBBB

Two women have benign pituitary tumors. Which hormones are being oversecreted by the pituitary tumors in the following patients? One woman has lost weight and complains of being hot all the time; she presents as thin and nervous with tachycardia and exophthalmos. hypersecretion of TSH causing hyperthyroid The second woman has gained weight in her abdomen and presents with a round face, thin arms, and legs with stretch marks; she says that at her last checkup her doctor told her she was prediabetic. hypersecretion of ACTH causing hypercortisolism Hypopituitarism is characterized by a decreased secretion of pituitary hormones. True or False? TRUE In children, a deficiency of ___ hormone interferes with linear bone development, resulting in short stature or dwarfism. growth hormone GH deficiency may result in dwarfism. True or False? TRUE Rationale: Laron-type dwarfism is caused by a genetic inability to produce normal amounts of GH What is somatopause? Somatopause is defined as the decline in growth hormone production that occurs with the aging process.

Let's discuss the types of DM Our author identifies 4 types of diabetes mellitus (see Chart 41-3) and compares Type 1 and Type 2 DM in table 41-8. Below is a brief review of each type. Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is characterized by the destruction of pancreatic beta cells. Beta cell destruction varies by individual, but is usually more rapid in infants and children and slower in adults. In fact, the presenting signs and symptoms in children may be diabetic ketoacidosis (DKA), rather than the typical clinical manifestations of polyuria, polydipsia, and polyphagia. Why is DKA more likely to develop in type 1 diabetes? The reason - the beta cells are destroyed and there is an absolute lack of insulin. The 2 types are - Type 1A Immune-Mediated Diabetesautoimmune disorderarises from a genetic predisposition, an environmental triggering event (like an infection), and a T-lymphocyte-mediated hypersensitivity reaction against beta cell antigens Type 1B Idiopathic Diabetesrare beta cell destruction without evidence of autoimmunitystrongly inherited disordercharacterized by varying degrees of insulin deficiency with periodic episodes of DKA

How does type 2 DM develop?

Type 2 DM develops from metabolic dysfunction characterized by elevated blood sugar levels due to pancreatic dysfunction and insulin resistance in tissues like skeletal muscles, adipose tissue and the liver. The critical risks of this form of diabetes include the following interrelationship of factors: genetic - positive family history with a 2-4 times increased risk epigenetic - heritable changes in gene function without changing the nucleotide sequence resulting in predisposition to DM behavioral - obesity and physical inactivity environmental - unhealthful food, refined carbohydrates, barriers to physical activity, stress. Insulin resistance is the failure of target tissues (muscles, fat, and liver) to insulin. As long as the pancreas can make enough insulin to overcome the weak response of the cells in response to insulin, blood glucose levels stay in the healthy range. The mechanisms leading to impaired secretion of insulin by the beta cells include: decrease in beta cell mass (genetic or epigenetic factors) increased apoptosis or regeneration of beta cells beta cell exhaustion due to long-standing insulin resistance.

Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is defined as a condition of hyperglycemia accompanied by a relative insulin deficiency. Of the 30 million people who currently have diabetes in the United States about 90% have Type 2 DM. It is an immensely significant public health issue of this century and the 5th leading cause of death worldwide (Vagula, 2015 (Links to an external site.)). While we used to believe that this was just a condition of individuals, who were older and overweight, we are seeing a rise of type 2 DM in obese children and adolescents. Certain racial and ethnic groups are also more likely to develop type 2 diabetes including African Americans, Mexican Americans, American Indians, Native Hawaiians, Pacific Islanders, and Asian Americans. Other at risk individuals include those with metabolic syndrome. Concomitants of metabolic syndrome are listed in Chart 41-5 of your text. Metabolic syndrome is diagnosed by >3 of the following characteristics: abdominal obesity (central obesity): waist circumference >35 inches in women or >40 inches in men triglycerides: >150 mg/dL high-density lipoproteins: <50 mg/dL in women and <40 in men blood pressure: >130/85 mm Hg fasting plasma glucose: >100 mg/dL.

Take some time to review the effect of growth hormone on protein synthesis and growth and its anti-insulin effects.

What hormones are important for normal body growth? Growth hormone is essential for normal body growth and maturation. It does not work alone but in conjunction with other hormones. Now review the stimulation and inhibitory effects on GHRH release along with the glucose sparing and growth and diabetogenic effects.

What is primary adrenal cortical insufficiency?

What is primary adrenal cortical insufficiency? Addison disease is a condition in which adrenal cortical hormones are deficient and ACTH levels are elevated due to the lack of feedback inhibition. It is a chronic metabolic disorder requiring lifetime hormone replacement therapy. It is caused by damage to the adrenal cortex - autoimmune disease, infections (tuberculosis, HIV, fungal infections), hemorrhage into the adrenal glands, or tumors.

Discuss the methods of diagnostic testing for diabetes. Fasting plasma glucose (FPG) - plasma glucose levels after food withheld for 8 hours; normal <100 mg/dL Random (casual) blood glucose test - plasma glucose levels without regard to last meal; normal <200 mg/dL Oral glucose tolerance test (OGTT) - screening test for diabetes; ability to store glucose by removing it from the blood after intake of 75 g of concentrated glucose solution; plasma glucose levels checked at 1 and 2 hours post intake of concentrated glucose solution Capillary blood glucose monitoring - finger-stick method for measuring blood or plasma glucose levels using test strips and glucometer Continuous glucose monitoring (CGM) - small catheter implanted in subcutaneous tissue to provide frequent samples of glucose levels throughout a 24-hour period Glycosylated hemoglobin (HbA1C or A1C) - makes up 2-6% of total hemoglobin; index of blood glucose levels over the previous 6-12 weeks; normal <6% Urine ketone testing - not standard testing except in individuals with type 1 diabetes who are at risk for DKA and in pregnant diabetic women; normal - no ketones

What is the constellation of abnormalities in metabolic syndrome? hyperglycemia intra-abdominal obesity increased blood triglyceride levels decreased HDL levels increased blood pressure systemic inflammation Type 2 diabetes is more common than type 1. True or False? TRUE Rationale: Type 1A DM is an autoimmune disorder affecting only 5-10% of the diabetic population. Type 2 DM is associated with risk factors like obesity, poor diet, and sedentary lifestyle - about 90% of diabetics are type 2. Type 1 diabetes mellitus is characterized by destruction of the pancreatic beta cells with an absolute lack of insulin, an elevation in blood glucose, and a breakdown of body fats and protein.

41.7 q

What occurs when ketone production by the liver exceeds cellular use and renal excretion? diabetic ketoacidosis (DKA) Which is not a long-term, chronic complication of diabetes mellitus? D. hyperglycemic hyperosmolar state Rationale: HHS is an acute complication of diabetes. The other 3 conditions result from hyperglycemia over a longer period of time. Nephropathy and retinopathy are caused by increased blood glucose levels that cause binding of excess glucose to the basement membranes of the blood vessels of the kidneys and eyes. Neuropathy is due to swelling and demyelination of nervous tissue.

How is hypothalamic-pituitary function assessed? The main assessment procedures include:

radioimmunoassay (RIA) - radioactive versions of a substance, or isotopes of the substance, are mixed with antibodies and inserted in a sample of blood; the non-radioactive substance in the blood takes the place of the isotope in the antibodies leaving the radioactive substance free; the amount of free isotope is measured to see how much of the original substance was in the bloodamount of anterior pituitary hormone levelsamount of target gland hormone levels magnetic resonance imaging (MRI) - imaging of hypothalamus and pituitaryevaluate structures for abnormalityevaluate tumor presence, location, and spread hypothalamic-pituitary function test - stimulation or suppression of hormone to identify normal or abnormal actionrapid ACTH stimulation testGH suppression test

Our focus for this portion of the lesson is on the anterior pituitary gland and primarily, the hormones related to growth and metabolism. The pituitary is considered the master gland in that it coordinates multiple functions through the release of hormones to target organs. The hypothalamus-pituitary axis functions as follows:

releasing hormones from the hypothalamus signal the anterior pituitary to release a specific hormone into the blood hormones from the anterior pituitary signal specific peripheral glands.