AP Chapter 22 Endocrine System PDF

## UNIT VI The Endocrine System ### SUMMARY REVIEW #### Mechanisms of Hormonal Alterations 1. Abnormalities in endocrine function may be caused by hypersecretion or hyposecretion of hormones or alterations in transport molecules. 2. Endocrine abnormalities may also be caused by alterations in rece...

## UNIT VI The Endocrine System ### SUMMARY REVIEW #### Mechanisms of Hormonal Alterations 1. Abnormalities in endocrine function may be caused by hypersecretion or hyposecretion of hormones or alterations in transport molecules. 2. Endocrine abnormalities may also be caused by alterations in receptor function through a variety of mechanisms: - a decrease in the number of receptors - receptor insensitivity to the hormone - the presence of antibodies against specific receptors - defects in second-messenger generation or postreceptor defects 3. Abnormally high levels of circulating hormones sometimes are caused by hormone release from tissues outside the endocrine system (ectopic foci) that may not respond to normal feedback mechanisms, in which case they are said to function autonomously. #### Alterations of the Hypothalamic-Pituitary System 1. Dysfunction in the release of hypothalamic hormones probably is related to interruption of the connection between the hypothalamus and pituitary - namely, the pituitary stalk. 2. Disorders of the posterior pituitary include SIADH secretion and DI. SIADH secretion is characterized by abnormally high ADH secretion; DI is characterized by abnormally low ADH secretion. 3. In SIADH, high ADH levels interfere with renal free water clearance, leading to hyponatremia and hypoosmolality. SIADH secretion is associated with certain forms of cancer, apparently because of ectopic secretion of ADH by tumor cells. 4. DI may be neurogenic, caused by insufficient amounts of ADH, or nephrogenic, caused by an inadequate response to ADH. Its principal clinical features are failure to concentrate urine with polyuria and polydipsia. Dipsogenic polyuria occurs when excessive fluid intake lowers the plasma osmolarity to the point that it falls below the threshold for ADH secretion. 5. Hypopituitarism is dysfunction of the anterior pituitary that causes failure of hormonal functions. Symptoms may be mild to severe. 6. Causes of hypopituitarism include pituitary infarction, space-occupying lesions such as tumor or aneurysm, surgical removal, or infections. Symptoms are variable depending on which hormones are deficient (e.g., TSH, ACTH, or GH). 7. Hyperpituitarism is caused by pituitary adenomas. These are usually benign slow-growing tumors that arise from cells of the anterior pituitary. 8. Expansion of a pituitary adenoma causes neurologic and secretory effects. Pressure from the expanding tumor causes hyposecretion of cells, dysfunction of the optic chiasm (leading to visual disturbances), and dysfunction of the hypothalamus and some cranial nerves. 9. Hypersecretion of GH causes acromegaly in adults and giantism in children. Pituitary adenoma is the most common cause of acromegaly. 10. Prolonged, abnormally high levels of GH lead to proliferation of body and connective tissues. Renal, thyroid, cardiovascular, and reproductive dysfunctions develop slowly, together with a change in bony proportions and insulin resistance. 11. GH deficiency in children results in growth failure and fasting hypoglycemia. Adult GH deficiency results in fatigue, osteoporosis, and increased mortality. 12. Pituitary prolactinomas, renal failure, and medications can result in increased levels of prolactin and affect reproductive organs and function in both men and women. #### Alterations of Thyroid Function 1. Thyrotoxicosis is a general condition in which TH levels are elevated and produce an exaggerated physiologic response in tissues. The condition can be primary, secondary, or subclinical. 2. Hyperthyroidism has a range of endocrine, reproductive, gastrointestinal, integumentary, and ocular manifestations. These are caused by increased circulating levels of TH and by stimulation of the sympathetic division of the autonomic nervous system. 3. Graves disease, the most common form of hyperthyroidism, is caused by thyroid-stimulating immunoglobulins that stimulate thyroid TSH receptors, resulting in thyroid hyperplasia and increased synthesis of TH. 4. Manifestations of Graves disease can include symptoms of hyperthyroidism, diffuse thyroid enlargement, and disorders of the skin and eyes and, occasionally, the hands. 5. The cutaneous manifestation of Graves disease is pretibial myxedema, a condition characterized by subcutaneous swelling of the legs and feet. 6. Ocular manifestations of Graves disease are caused by hyperactivity of the sympathetic division of the autonomic nervous system and by immune-induced infiltration of extraocular muscles, orbital fat accumulation, and edema (exophthalmos). 7. Toxic multinodular goiter and solitary toxic adenoma occur when some hyperplastic, hyperfunctioning thyroid nodules autonomously secrete TH, causing hyperthyroidism and producing symptoms similar to those of Graves disease. 8. Toxic multinodular goiters result from multiple functioning adenomas. 9. Thyrotoxic crisis (thyroid storm) is a severe form of hyperthyroidism that often is associated with physiologic stress. Without treatment, death occurs quickly. 10. Hypothyroidism is caused by deficient production of TH by the thyroid gland. The condition may be primary, secondary, or subclinical. 11. Causes of primary hypothyroidism include iodine deficiency, autoimmune thyroiditis, subacute or painless thyroiditis, silent or subacute lymphocytic thyroiditis, iatrogenic hypothyroidism, and postpartum thyroiditis. 12. Autoimmune thyroiditis (Hashimoto disease) is associated with lymphocyte infiltration, antibody activation of natural killer cells, induction of apoptosis with gradual loss of thyroid function, and hypothyroidism. 13. Subacute thyroiditis, a form of hypothyroidism, is a self-limited nonbacterial inflammation of the thyroid gland. The inflammatory process damages follicular cells, causing leakage of triiodothyronine (T3) and tetraiodothyronine (thyroxine) (T4). Hyperthyroidism then is followed by transient hypothyroidism, which is corrected by cellular repair and a return to normal levels in the thyroid. 14. Secondary hypothyroidism is caused by hypothalamic-pituitary dysfunction in which TRH and TSH are not produced in sufficient amounts. 15. Thyroid carcinoma is a relatively rare cancer. The most consistent causal risk factor associated with thyroid carcinoma is exposure to ionizing radiation, especially in childhood. 16. Hypothyroidism affects all body systems. Symptoms depend on the degree of TH deficiency. Common manifestations include decreased energy metabolism and loss of heat production. 17. Myxedema is the characteristic sign of hypothyroidism. Myxedema is caused by alterations in connective tissue with water-binding proteins. The excess water leads to thickened mucous membranes and edema, particularly around the eyes and in the hands and feet. 18. Myxedema coma is a severe form of hypothyroidism, which may be life-threatening without emergency medical treatment. It occurs with thyroid agenesis and results in hypothyroidism, growth failure, and intellectual disability from absence of thyroxine. 19. Papillary and follicular thyroid carcinomas are the most common thyroid malignancies probably caused by exposure to ionizing radiation, particularly during childhood. Thyroid nodules are present with normal thyroxine levels. #### Alterations of Parathyroid Function 1. Hyperparathyroidism may be primary, secondary, or tertiary and is characterized by greater than normal secretion of PTH. - Primary hyperparathyroidism is usually caused by a parathyroid adenoma and results in greater than normal secretion of PTH that regulates calcium and PTH levels. Manifestations include chronic hypercalcemia, increased bone resorption, and hypercalciuria. - Secondary hyperparathyroidism is a compensatory response to hypocalcemia and often occurs with chronic renal failure or chronic vitamin D deficiency. - Tertiary hyperparathyroidism is excessive secretion of PTH and hypercalcemia that occurs after long-standing hypocalcemia. 2. Pseudohypoparathyroidism and familial hypocalciuric hypercalcemia are inherited conditions. In pseudohypoparathyroidism there is resistance to PTH. 3. Hypoparathyroidism, defined by abnormally low PTH levels, is caused by thyroid surgery, autoimmunity, or genetic mechanisms. 4. The lack of circulating PTH in hypoparathyroidism causes depressed serum calcium levels, increased serum phosphate levels, decreased bone resorption, and eventual hypocalciuria. #### Dysfunction of the Endocrine Pancreas: Diabetes Mellitus 1. Diabetes mellitus is a group of diseases characterized by hyperglycemia resulting from defects in insulin secretion or insulin action, or both. The two most common types of diabetes mellitus are type 1 and type 2. 2. A diagnosis of diabetes mellitus is based on glycosylated hemoglobin (HbA1c) levels, fasting plasma glucose (FPG) levels, and 2-hour plasma glucose levels during oral glucose tolerance testing (OGTT). 3. Type 1 diabetes mellitus includes an autoimmune (most common) and a nonimmune type. The immune type (type 1A) is associated with genetic susceptibility, environmental factors, and autoantibody, T-cell, and macrophage destruction of pancreatic beta cells with loss of insulin production and a relative excess of glucagon. Antibodies also can be formed against glutamic acid decarboxylase and insulin. 4. Nonimmune type diabetes (type 1B) occurs secondary to other disease. 5. Type 2 diabetes mellitus is caused by genetic susceptibility that is triggered by environmental factors. The most compelling environmental risk factor is obesity. Insulin production continues but the weight and number of beta cells decrease. 6. Several mechanisms of insulin resistance (hyperinsulinemia) cause reduced glucose uptake and metabolism in type 2 diabetes. These mechanisms include alteration in the production of adipokines by adipose tissue (i.e., leptin resistance), elevated levels of serum free fatty acids and intracellular lipid deposits, release of inflammatory cytokines from adipose tissue, reduced insulin-stimulated mitochondrial activity, and obesity-associated insulin resistance. 7. In type 2 diabetes, amylin deficiency results in increased glucagon secretion and hyperglycemia. 8. Decreased ghrelin and amylin levels and decreased beta-cell response to glucagon-like peptide have been associated with insulin resistance and type 2 diabetes. 9. Other specific types of diabetes mellitus include MODY associated with autosomal dominant gene mutations and gestational diabetes associated with onset of glucose intolerance during pregnancy. 10. Acute complications of diabetes mellitus include hypoglycemia, DKA, HHNKS, the Somogyi effect, and the dawn phenomenon. 11. Hypoglycemia is a lowered blood glucose level that may be related to exogenous (i.e., insulin shock or insulin reaction), endogenous, or functional causes. 12. Symptoms of hypoglycemia are divided into adrenergic, caused by activation of the sympathetic nervous system; and neuroglycopenic, reflecting defective central nervous system metabolism resulting from impaired energy generation. 13. DKA develops when there is an absolute or relative deficiency of insulin and an increase in the amounts of insulin counter-regulatory hormones of catecholamines, cortisol, glucagon, and GH; increased lipolysis; and accelerated gluconeogenesis and ketogenesis. It is most common in type 1 diabetes, but also occurs in type 2. 14. HHNKS is pathophysiologically similar to DKA, although levels of FFAs are lower in HHNKS and lack of ketosis indicates that some level of insulin is present. The hyperosmolar state can cause osmotic diuresis and profound dehydration, causing coma. 15. The Somogyi effect is a combination of hypoglycemia with rebound hyperglycemia caused by effects of counter-regulatory hormones. It is most common in persons with type 1 diabetes mellitus and in children. 16. The dawn phenomenon is an early morning rise in glucose levels caused by nocturnal elevations of GH concentration. 17. Chronic complications of diabetes mellitus are related to chronic hyperglycemia and include microvascular disease (e.g., retinopathy, nephropathy, and neuropathy), macrovascular disease (e.g., CAD, stroke, and peripheral vascular disease), and infection. Metabolic changes contributing to complications include oxidative stress, shunting of glucose to the polyol pathway, activation of protein kinase C, formation of AGEs, and accumulation of hexosamines. 18. Microvascular complications are associated with vascular alterations in the endothelium and the basement membrane as well as thrombosis. 19. Diabetic retinopathy is caused by several mechanisms including microvascular changes and thrombosis that lead to microvascular occlusion, retinal ischemia, increased vascular permeability, microaneurysm formation, hemorrhages, and neovascularization with loss of vision. 20. Diabetic nephropathy is related to hyperglycemia, hyperperfusion, oxidative stress, and inflammation with glomerular enlargement and glomerular basement membrane thickening, diffuse intercapillary glomerulosclerosis, expansion of the mesangial matrix, and progressive renal failure. 21. Diabetic neuropathies may be caused by vascular and metabolic mechanisms, or by a combination of both, with axonal and Schwann cell degeneration and abnormalities in sensory and motor nerve conduction velocity, and involvement of the autonomic nervous system. 22. Macrovascular disease associated with diabetes mellitus is associated with hyperglycemia, hyperlipidemia, inflammation, and altered endothelial function. 23. The incidence of coronary heart disease, peripheral vascular disease, and stroke is greater in persons with diabetes than in nondiabetic individuals. 24. CAD and stroke in diabetes are a consequence of accelerated atherosclerosis, hypertension, and increased risk for thrombus formation. 25. Peripheral artery disease is a consequence of neuropathy and occlusion of large and small arteries with an increased risk of ischemia, necrosis, and amputation. 26. Individuals with diabetes are at risk for a variety of infections related to sensory impairment, vascular complications, impaired white blood cells and suppressed immunity, rapid proliferation of pathogens, and delayed wound healing. #### Alterations of Adrenal Function 1. Disorders of the adrenal cortex are related to hyperfunction or hypofunction. No known disorders are associated with hypofunction of the adrenal medulla, but medullary hyperfunction causes clinically defined syndromes. 2. Hypercortisolism is divided into ACTH-dependent (Cushing disease or ectopic ACTH syndrome) and ACTH-independent (adrenal adenoma or adenocarcinoma) mechanisms. 3. Cushing disease is excessive anterior pituitary ACTH production, most commonly by an ACTH-secreting pituitary microadenoma. 4. Cushing syndrome occurs whenever there is an excessive level of cortisol regardless of cause. Exogenous forms result from exogenous administration of glucocorticoids. Endogenous forms are either corticotropin dependent (most common and caused by an ACTH-secreting pituitary tumor) or corticotropin independent (usually caused by an adrenal cortical tumor). 5. Individuals with Cushing disease lose diurnal and circadian patterns of ACTH and cortisol secretion, and they lack the ability to increase secretion of these hormones in response to a stressor. Individuals experience weight gain, glucose intolerance, protein wasting, bone disease, hyperpigmentation, and immunosuppression. 6. Congenital adrenal hyperplasia is an autosomal recessive disorder with inadequate synthesis of cortisol and increased levels of ACTH that cause adrenal hyperplasia and overproduction of mineralocorticoids or androgens. 7. Primary hyperaldosteronism is a disorder of excessive aldosterone secretion usually caused by an adrenal cortical adenoma or bilateral nodular hyperplasia. The condition is characterized by hypertension, hypokalemia, renal potassium wasting, and neuromuscular manifestations. 8. Secondary hyperaldosterone secretion is related to a variety of conditions associated with elevated renin release and activation of angiotensin II. These include decreased circulating blood volume, decreased renal blood supply, elevated estrogen levels, Bartter's syndrome, and renin-secreting tumors. 9. Adrenal tumors, either adenomas or carcinomas, can autonomously secrete androgens or estrogens. 10. Hypofunction of the adrenal cortex can affect glucocorticoid or mineralocorticoid secretion or both. Hypofunction can be caused by a deficiency of ACTH or by a primary deficiency in the gland itself. 11. Hypocortisolism (low levels of cortisol) is caused by inadequate adrenal stimulation by ACTH or by primary cortisol hyposecretion. Primary adrenal insufficiency is termed Addison disease. 12. Addison disease is characterized by elevated ACTH levels with inadequate corticosteroid synthesis and output. Causes include idiopathic autoimmune disease, tuberculosis of the adrenal gland, familial adrenal insufficiency, amyloidosis, metastatic destruction of the adrenal glands, and adrenal hemorrhage. 13. Manifestations of Addison disease are related to hypocortisolism and hypoaldosteronism. Symptoms include weakness, fatigability, hypoglycemia and related metabolic problems, lowered response to stressors, vitiligo, hyperpigmentation, and manifestations of hypovolemia and hyperkalemia. 14. Secondary hypercortisolism is characterized by low to absent ACTH levels, leading to inadequate adrenal stimulation, adrenal atrophy, and decreased corticosteroidogenesis. The most common cause is withdrawal of exogenous administration of glucocorticoids. Manifestations are similar to those of Addison disease only without hyperpigmentation. 15. Hyperfunction of the adrenal medulla is caused by a pheochromocytoma, which is a catecholamine-producing tumor. Symptoms of catecholamine excess are related to their sympathetic nervous system effects and include hypertension, palpitations, tachycardia, glucose intolerance, excessive sweating, and constipation.