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Patho2 chapter40 student1


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Patho2 chapter40 student1

  1. 1. Disorders of Endocrine Function Chapter 40
  2. 2. Endocrine Disorders Etiology of Endocrine Disorders • Hyposecretion or hypersecretion can occur in the: – Hypothalamus/pituitary – Hormone-producing gland – Target tissue • Etiology can be: – Congenital – Infectious – Autoimmune – Neoplastic – Idiopathic – Iatrogenic
  3. 3. Elevated or Depressed Hormone Levels• Failure of feedback systems• Dysfunction of an endocrine gland• Secretory cells are unable to produce, obtain, or convert hormone precursors• The endocrine gland synthesizes or releases excessive amounts of hormone or not enough hormone• Increased hormone degradation or inactivation• Ectopic hormone release• Target cell failure
  4. 4. Endocrine Disorders: Classification • Endocrine disorders involving control by anterior pituitary gland are classified as: – Primary: intrinsic malfunction of the hormone-producing target gland – Secondary: malfunction of the hypothalamus/pituitary cells that control the hormone-producing target gland
  5. 5. Alterations of theHypothalamic-Pituitary System
  6. 6. Endocrine Disorders
  7. 7. Diseases of the Anterior Pituitary• Hypersecretion of growth hormone (GH) – Acromegaly • Hypersecretion of GH during adulthood • (cause: GH-secreting pituitary adenoma) – Gigantism • Hypersecretion of GH in children & adolescents
  8. 8. Diseases of the Anterior Pituitary Giantism: Hypersecretion of growth hormone (GH)(excess somatotropin [GH] BEFORE epiphyseal closure)
  9. 9. Diseases of the Anterior Pituitary • Acromgaly: Hypersecretion of growth hormone (GH)(excess somatotropin [GH] AFTER epiphysealclosure)
  10. 10. Thyroid Gland Disorders
  11. 11. Thyroid Hormone Disorders • Hypothyoidism – Congenital – Acquired • Hyperthyroidism
  12. 12. Hypothyroidism • CONGENITAL HYPOTHYROIDISM (cretinism) is typically due to thyroid dysgenesis • Majority are PRIMARY, due to intrinsic dysfunction of the thyroid gland • PRIMARILY LYMPHOCYTIC THYROIDITIS (Hashimoto or autoimmune thyroiditis) Acquired • Irradiation of the thyroid gland • Surgical removal of thyroid tissue • Iodine deficiency
  13. 13. Cretinism Congential hypothyroidism: can be endemic (iodine deficiency), genetic, or sporadicDelayed bone maturation, puberty, mentalretardation, abdominal protrusion with umbilical hernia
  14. 14. A 3-month-old male was diagnosed withcongenital hypothyroidism. If left untreated, thechild would have:A. mental retardation and stunted growth.B. increased risk of childhood thyroid cancer.C. hyperactivity and attention deficit disorder.D. liver, kidney, and pancreas failure.
  15. 15. ETIOLOGY AND PATHOGENESIS:Hypothyroidism: Primary Hypothyroidism • Iodine is essential for T3 and T4 synthesis • Deficiency in iodine leads to lack of T3/T4 but does not affect thyroglobulin levels • Insufficient hormone available to inhibit secretion of TSH • Increased TSH causes thyroid cells to secrete large amounts of thyroglobulin, which leads to a goiter
  16. 16. GOITER
  17. 17. Many vegetables are goiterogens
  18. 18. ETIOLOGY AND PATHOGENESIS:Hypothyroidism: Secondary hypothyroidism is caused by defects in TSH production and can result from: • Severe head trauma • Cranial neoplasms • Brain infections • Cranial irradiation • Neurosurgical procedures
  19. 19. Clinical ManifestationsInfants Children/Adults• Dull • Decreased basal metabolic rate • Weakness, lethargy, cold appearance, thick, protuberant intolerance, decreased appetite tongue, and thick lips result in • Bradycardia, narrowed pulse feeding difficulties pressure, and mild/moderate weight• Prolonged neonatal jaundice gain• Poor muscle tone • Elevated serum cholesterol and• Bradycardia, mottled extremities triglycerides • Enlarged thyroid, dry skin, constipation• Umbilical hernia • Depression, difficulties with• Hoarse cry concentration/memory • Menstrual irregularity
  20. 20. Hashimoto’s thyroiditis• Chronic lymphocytic thyroiditis• Infiltration by lymphocytes• Destruction of thyroid by antibodies• Goiter formation is common• Can occur with other autoimmune diseases: Type 1 DM, vitiligo
  21. 21. CLINICAL FEATURES of Hashimoto’s Thyroiditis• Onset of disease – 30-60 years of age• 5 times more common in females than males• Patients have  T4 and  TSH• Patients have enlarged thyroid (goiter)• Symptoms include: – Dry skin, tiredness, weight gain, puffy face, intolerance to cold, mild depression• Treatment – thyroid hormone replacement
  22. 22. Hypothyroidism: characteristic sign of long-standing disease
  23. 23. Myxedema• Severe or prolonged thyroid deficiency• Accumulation of glycosaminoglycans in interstitial spaces Myxedema (coma) • Sluggishness • Cool skin, ↑cholest erol
  24. 24. DIAGNOSIS: Hypothyroidism • Primary hypothyroidism will manifest as elevated TSH • Low levels of T3 and T4 may not occur until later in the disease course • Hypothalamic-pituitary dysfunction results in low levels of TSH and T4
  25. 25. TREATMENT: Hypothyroidism: • Treatment goal is return of euthyroid state • Oral levothyroxine is used to replace or supplement hormone production • Resolution of symptoms occurs over weeks • Intravenous levothyroxine used for myxedema coma
  26. 26. Hyperthyroidism • Primary—autonomous • Secondary—mediated through stimulation of TSH receptors by substances such as TSH • Autoimmune—related to TSH receptor antibodies
  27. 27. ETIOLOGY AND PATHOGENESIS: Hyperthyroidism What causes Hyperthyroidism? • Pituitary adenoma • Thyroid carcinoma • Autoantibodies that bind and stimulate TSH receptors on the thyroid gland leading to a diffuse toxic goiter (Graves disease) • Ingestion of thyroid hormone preparations or excessive iodides
  28. 28. CLINICAL MANIFESTATIONS: Hyperthyroidism • Changes in behavior, insomnia, restlessness, tremor, irritability, p alpitations, heat intolerance, diaphoresis, inability to concentrate that interferes with work performance • Increased basal metabolic rate leads to weight loss, although appetite and dietary intake increase • Amenorrhea/scant menses
  29. 29. Graves Disease: autoimmune most common form of hyerpthyroidismEdema of orbit, exopthalmos, extrocular muscle weakness
  30. 30. Antibodiesmimic TSH bybinding toandactivatingTSH receptors
  31. 31. Clinical Features of Graves’ Disease• Onset of disease – 20-50 years of age• 10 times more common in females than males• Patients have goiter with thyroid gland 2-3 times normal size• Symptoms include: – Nervousness, fatigue, weight loss; 50% have thyroid- associated ophthalmopathy with eyelid retraction and periorbital edema• Treatment – anti-thyroid drugs, surgery, and radioactive iodine ablation
  32. 32. Graves’ Disease: Diagnosis• Diagnosis often made on clinical symptoms alone• Elevated T3 and T4; low TSH – Why?
  33. 33. Comparison of Graves’ disease and Hashimoto’s thyroiditis HYPOHYPER
  34. 34. A 35-year-old female with Graves disease is admitted to a medical-surgical unit. Lab tests would most likely reveal:A. high levels of circulating thyroid-stimulatingantibodies.B. ectopic secretion of thyroid-stimulatinghormone (TSH).C. low circulating levels of thyroid hormones.D. stimulation of thyroid-binding globulin.
  35. 35. CLINICAL MANIFESTATIONS: Hyperthyroidism Thyroid storm—form of life-threatening thyrotoxicosis that occurs when excessive amounts of thyroid hormones are acutely released into circulation • Manifestations – Elevated temperatures, tachycardia, arrhythmias – Extreme restlessness, agitation, and psychosis – Vomiting, nausea, diarrhea, and jaundice
  36. 36. DIAGNOSIS: Hyperthyroidism: DIAGNOSIS Primary hyperthyroidism will manifest as: • Undetectable TSH levels • Elevated serum T4 and T3 TREATMENTS: • Symptomatic relief: Beta blockers • Reduce circulating hormones: methimazole, propylthioricil • More permanent treatment: surgical removal of thyroid, radioactive iodine
  37. 37. TREATMENT: Hyperthyroidism Treatment of thyroid storm • Aggressive management to achieve metabolic balance • Antithyroid drugs are given followed by iodine administration • Beta-blockers to alleviate symptoms • Antipyretic therapy • Fluid replacement • Glucocorticoids
  38. 38. Alterations of Thyroid Function: Table 40.2 Hypothyroidism Hyperthyroidism Basal metabolic rate Sympathetic ANS Weight Temp tolerance GI function Cardio/Respiratory function Reproductive Muscle tone Appearance General behavior
  39. 39. Adrenal Gland Disorders
  40. 40. Adrenal Gland 1- Adrenal cortex: • Constitutes 90% of gland volume • Secrete steroid hormones (adrenocortical hormones): - Mineralocorticoids (aldosterone) SALT - Glucocorticoids (cortisol) SUGAR - Adrenal androgens SEX 2- Adrenal medulla: • Secrete catecholamines: - Norepinephrine (NE, nonadrenaline) Main hormones - Epinephrine (E, adrenaline) - Dopamine
  41. 41. Disorders of the Adrenal Cortex • Hypoadrenalism 1- Primary adrenal insufficiency (Addison’s disease) 2- Secondary adrenal insufficiency: CRH, ACTH, result from: - pituitary or hypothalamic disease. - long-term suppression of hypothalamic-pituitary-adrenal axis by glucocorticoids adrenal atrophy. • Hyperadrenalism 1- Cushing’s syndrome: cortisol production 2- Primary hyperaldosteronism (Conn’s syndrome): aldosterone production 3- Congenital adrenal hyperplasia: caused by enzymatic abnormalities in steroid synthesis.
  42. 42. Adrenocortical Insufficiency Unable to produce adequate levels of cortisol
  43. 43. Adrenocortical Insufficiency • Disorders of the adrenal cortex – Adrenocortical hypofunction • PRIMARY: Addison disease – Destruction of the adrenal gland through: • Idiopathic or autoimmune mechanisms • Tuberculosis, • Trauma or hemorrhage, • Fungal disease • Neoplasia ENTIRE CORTEX
  44. 44. Addison’s Disease: Clinical Manifestations• Insufficient Adrenal hormones: chronic fatigue, muscle weakness, loss of appetite, weight loss, low BP, dehydration, cardiac arrythmias, bronzed appearance
  45. 45. o By the time of the missile crisis, Kennedy was taking antispasmodics to control colitis; antibiotics for a urinary tract infection; and increased amounts of hydrocortisone and testosterone, along with salt tablets, to control his adrenal insufficiency and boost his energy.
  46. 46. Adrenocortical Insufficiency • SECONDARY: Hypothalamic-Pituitary Dysfunction – usually iatrogenic, related to corticosteroid therapy, which suppresses ACTH, CRH – May also occur due to damage of the anterior pituitary or hypothalamus by tumors, infection, radiation, postpartum necrosis, trauma, or surgery
  47. 47. Adrenocortical Insufficiency Addisonian crisis/acute adrenal insufficiency • Life-threatening condition caused by inadequate levels of glucocorticoids and mineralocorticoids in circulation • May occur with acute withdrawal of corticosteroids or due to periods of stress or trauma
  48. 48. Adrenocortical Insufficiency Clinical manifestations • Early signs include: – anorexia, – weight loss – weakness – malaise – apathy – electrolyte disturbances – hyperpigmentation of skin • Diminished vascular tone, reduced cardiac output, inadequate circulating blood volume; can lead to cardiovascular collapse
  49. 49. Adrenocortical Insufficiency Diagnosis • Patient history and physical exam, decreased plasma cortisol levels • ACTH provocation test may be administered • Abdominal CT/MRI may be performed to evaluate the size of the adrenal glands Treatment • Replacing the absent or deficient hormones in a manner that mimics natural production • 2/3 of the daily dosage is given in the morning and 1/3 in the evening • Treatment of adrenal crisis – Intravenous glucocorticoids
  50. 50. Alterations of Adrenal FunctionDisorders of the adrenalcortex: HYPERCORTISOLISM – Cushing disease • Excessive ANTERIOR PITUITARY secretion of ACTH – Cushing syndrome • Excessive level of cortisol, regardless of cause
  51. 51. Hypercortisolism: Etiology and Pathogenesis • PRIMARY adrenocortical hyperfunction due to disease of the adrenal cortex (adrenal adenoma) • SECONDARY disease caused by hyperfunction of the anterior pituitary ACTH-secreting cells • TERTIARY disease caused by hypothalamic dysfunction or injury • EXOGENOUS STEROID use is the most common cause of Cushing syndrome in the United States
  52. 52. Causes of ACTHCushing’s Syndrome Most common cause
  53. 53. Cushing’s Syndrome Redistribution of adipose: Truncal obesity, moon face, buffalo hump Protein wasting: limb muscles Loss of collagen: thin skin, striae, bruising
  54. 54. Cushing Syndrome: Clinical Manifestations STRIAE BUFFALO HUMP MOON FACE
  55. 55. Cushing Syndrome: Clinical Manifestations Clinical manifestations: • Round face with flushed cheeks, “moon face” • Weight gain with excess total body fat, particularly in the abdomen • 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 • Demineralization of bone (osteoporosis) • Increased androgen production causing excessive hair production, acne, menstrual irregularities • Emotional changes
  56. 56. Characteristic physical features of individualswith Cushing syndrome include:A. weight loss and muscle wasting.B. truncal obesity and thin skin.C. pallor and swollen tongue.D. depigmented skin and eyelid lag.
  57. 57. Cushingism - Diagnosis
  58. 58. ACTH measurement Primary = low ACTH Secondary = high ACTHUrinary free cortisol levelsDexamethasone suppressiontest
  59. 59. Cushing Syndrome: Treatment Treatment is based on etiology • Exogenous dose reduction • Pituitary adenomas are treated surgically with transsphenoidal hypophysectomy, laser ablation, or radiation • Adrenal tumor is treated with unilateral adrenalectomy • Chemotherapeutic agents block cortisol production
  60. 60. Hyperaldosteronism: • Primary (Conn syndrome)—usually due to aldosterone-secreting tumors • Secondary—typically associated with poor kidney perfusion that stimulates the renin-angiotensin- aldosterone cascade (heart failure, reduced kidney perfusion, liver cirrhosis)
  61. 61. Hyperaldosteronism: • Aldosterone facilitates salt and water retention by the kidney with resultant potassium excretion • Typically low potassium level • Treatment includes spironolactone to increase sodium excretion and potassium retention • Sodium restriction and potassium replacement may also be necessary
  62. 62. Adrenal Medulla Disorders
  63. 63. PheochromocytomaEtiology and PathogenesisAdrenal medulla hyperfunction • Caused by tumors derived from the chromaffin cells of the adrenal medulla – Pheochromocytomas • Secrete catecholamines on a continuous or episodic basis
  64. 64. Pheochromocytoma: Clinical Manifestations
  65. 65. Pheochromocytoma: Diagnosis and Treatment • Diagnosed with abdominal CT/MRI • Treatment includes sympathetic blocking medications to manage blood pressure and surgical removal of the tumor • If surgery is contraindicated, medication to block catecholamine production is possible but surgery is the only curative therapy
  66. 66. Parathyroid Gland Disorders
  67. 67. Parathyroid Gland What does PTH do? • Increases serum calcium & decrease serum phosphate 1. Increase bone reabsorption of calcium 2. Increase kidney reabsorption of calcium 3. Decrease kidney reabsorption of phosphate 4. Increase Vitamin D production in kidneyParathyroid glandslocated at the upperand lower poles ofthe thyroid
  68. 68. Parathyroid Gland
  69. 69. Regulation of Calcium level
  70. 70. Regulation of Calcium level osteoblasts osteoclasts
  71. 71. Regulation of Blood CalciumPTH Calcitonin• Serum calcium levels provide the • Calcitonin produced by thyroid feedback to regulate parathyroid parafollicular cells also hormone (PTH) secretion influences the processing of• Decrease in calcium causes PTH calcium by bone cells release • Calcitonin controls calcium• Elevated calcium levels lead to suppression of PTH secretion content of blood by increasing bone formation by osteoblasts• PTH acts on bones, intestine, and and inhibiting bone renal tubules to increase calcium levels breakdown by osteoclasts• In bone, PTH increases osteoclastic • Calcitonin decreases blood activity calcium levels and promotes• PTH increases renal calcium conservation of hard bone reabsorption matrix
  72. 72. Parathyroid Disorders Hyperparathyroidism: PTH, Ca+2, Phosphorous (1) Primary hyperparathyroidism: • PTH, Ca+2, Phosphorous • Causes demineralization, extensive resorption • Hypercalcemia mostly affect the nervous system and kidney (2) Secondary hyperparathyroidism: secondary to conditions that cause chronic hypercalcemia of nonparathyroid cause: major causes: • Vitamin D-metabolite deficiencies • High phosphorus load
  73. 73. Stones, Bones, Groans, Moans• Kidney stones• Bone-related complications• Abdominal groans• Psychic moansEtiology: Genetic origin, Parathyroid adenoma, Hyperplasia ofparathyroid glands
  74. 74. Hyperparathyroidism Clinical manifestations • Kidney stones • Bone demineralization (osteoporosis) • Polyuria and dehydration • Anorexia, nausea, vomiting, constipation • Bradycardia, heart block, and cardiac arrest
  75. 75. Hyperparathyroidism Treatment • Surgical removal of parathyroid gland • Medical management includes hydration and ambulation to maintain bone density • For hypercalcemic crisis, rapid volume expansion with 0.9% NS to treat dehydration and improve glomerular filtration rate; diuretics to increase calcium excretion by the kidneys
  76. 76. A problem associated with chronichyperparathyroidism is:A. seizure disorder.B. vitamin D malabsorption.C. hyponatremia.D. osteoporosis and pathologic fractures.
  77. 77. Alterations of Parathyroid Function:HYPOPARATHYROIDISM– Abnormally low PTH levels– Usually caused by parathyroid damage in thyroid surgery
  78. 78. Parathyroid DisordersHypoparathyroidism: PTH, Ca+2, Phosphorous(1) Primary hypoparathyroidism: a) Idiopathic hypoparathyroidism * hormone-deficient hypoparathyroidism * PTH b) Pseudohypoparathyroidism * hormone-sufficient, receptor-deficient hypoparathyroidism * PTH(2) Secondary hypoparathyroidism: result from other disorders.
  79. 79. HYPOPARATHYROIDISM Etiology • Parathyroid or thyroid surgery or surgery in the area of these glands; may be temporary or permanent • Permanent hypothyroidism can develop after thyroidectomy due to damage to parathyroid gland blood supply, postsurgical swelling, or fibrosis • Congenital lack of parathyroid tissue and idiopathic hypoparathyroidism are causes of hypoparathyroidism in children and infants • Autoimmune processes may target and damage the parathyroid glands
  80. 80. What happens to serum calcium? Causes lowered threshold for nerve and muscle excitationClinical manifestations• Circumoral numbness, paresthesias of the distal extremities, muscle cramps, fatigue, hyperirritability, anxiety, depression, ECG changes, increases in intracranial pressure• Severe symptoms include carpopedal spasm, laryngospasm, and seizures
  81. 81. Hypoparathyroidism Treatment • Acute hypocalcemic crisis (tetany, laryngospasm, and convulsions)—parenteral calcium administration and calcitriol, an activated form of vitamin D • Long-term treatment: oral calcium supplement with vitamin D
  82. 82. Antidiuretic Hormone (ADH) Disorders
  83. 83. Antidiuretic Hormone • ADH (vasopressin) secreted by the posterior pituitary gland in response to changes in blood osmolality • ADH acts directly on the renal collecting ducts and distal tubules, increasing membrane permeability to and reabsorption of water The single most important effect of antidiuretic hormone is to conserve body water by reducing the loss of water in urine
  84. 84. DIABETES INSIPIDUS: Antidiuretic HormoneDisorders: • Etiology and pathogenesis – Disorder of INSUFFICIENT ADH activity resulting in excessive loss of water in urine – DAMAGE to ADH-producing cells in the hypothalamus can result from: • Traumatic brain injury • Intracranial tumors • Neurosurgical procedures – Some pharmacologic agents can lead to abnormalities in ADH secretion
  85. 85. DIABETES INSIPIDUS: Antidiuretic HormoneDisorders • Central diabetes insipidus is due to the inability to produce and release ADH from the pituitary gland • Nephrogenic diabetes insipidus results from the INABILITY of the kidneys to respond to ADH due to chronic renal disease, serum electrolyte abnormalities, or drugs
  86. 86. SIADH: Antidiuretic Hormone Disorders Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Etiology • EXCESSIVE ADH from ectopic production due to several types of tumors, notably primary lung malignancies • Pulmonary tuberculosis • Drug-induced ADH secretion can occur
  87. 87. SIADH: Antidiuretic Hormone DisordersREMEMBERWhat does Aldosterone do?
  88. 88. Clinical ManifestationsDiabetes Insipidus SIADH• Polyuria, polydipsia • Hyponatremia• Low urine specific gravity • High urine osmolality• Hypernatremia due to water • Low serum osmolality • Cell swelling deficit • Weakness, muscle• Dry mucous membranes, poor cramps, postural BP skin turgor, decreased saliva changes, poor skin and sweat production turgor, fatigue, anorexia, lethargy• Disorientation, lethargy, seizur • Confusion, seizures, coma es
  89. 89. TreatmentDiabetes Insipidus SIADH• Daily replacement of ADH • Free water restriction with desmopressin (DDAVP) • If severe symptoms, IV• Free access to fluids administration of saline with diuretics is used• Home testing of urine • Hyponatremia should be specific gravity corrected slowly to avoid rapid changes in brain cell volume
  90. 90. The most common cause of elevated levels of antidiuretic hormone (ADH) secretion is:A. autoimmune disease.B. cancer.C. pregnancy.D. heart failure.
  91. 91. A 54-year-old patient with pulmonary tuberculosis (lung infection) is evaluated for syndrome of inappropriate ADH secretion (SIADH). Which of the following electrolyte imbalances would be expected in this patient?A. HyponatremiaB. HyperkalemiaC. HypernatremiaD. Hypokalemia