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Chapter 21 Alterations of Hormonal Regulation Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. Elevated or Depressed Hormone Levels Failure of feedback systems Dysfunction of an endocrine gland Excessive/inadequate hormone production Altered hormone inactivation/degradation Ectopic hormone release Nonendocrine Autonomous production, no feedback mechanisms Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 2 Target Cell Failure Receptor-associated disorders Decrease in number of receptors Impaired receptor function Presence of antibodies against specific receptors Antibodies that mimic hormone action Unusual expression of receptor function Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Intracellular Disorders Inadequate synthesis of a second messenger Cyclic adenosine monophosphate (cAMP) Failure of the target cell to produce anticipated hormonal response Faulty response to hormone-receptor binding • Failure to generate required second messenger • Abnormal response to the second messenger Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Alterations of the Hypothalamic-Pituitary System Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Diseases of the Posterior Pituitary Syndrome of inappropriate antidiuretic hormone (SIADH) secretion Ectopic secretion of ADH most common cause; also common after surgery For diagnosis, normal adrenal and thyroid function must exist Clinical manifestations • Related to enhanced renal water retention • Hyponatremia • Hypoosmolarity Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Diseases of the Posterior Pituitary Diabetes insipidus Insufficiency of ADH Polyuria and polydipsia Partial/total inability to concentrate the urine Neurogenic • Insufficient amounts of ADH Nephrogenic • Inadequate response to ADH Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Diseases of the Anterior Pituitary Pituitary is vascular and therefore vulnerable to ischemia and infarction Hypopituitarism Pituitary infarction • Sheehan syndrome • Hemorrhage • Shock Others: head trauma, infections, and tumors Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Diseases of the Anterior Pituitary Hypopituitarism Panhypopituitarism (all hormones absent) • ACTH deficiency • TSH deficiency • FSH and LH deficiency • GH deficiency Glucose intolerance Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Diseases of the Anterior Pituitary Hyperpituitarism Commonly due to a benign, slow-growing pituitary adenoma Manifestations • Headache and fatigue • Visual changes • Hyposecretion of neighboring anterior pituitary hormones Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Diseases of the Anterior Pituitary Hypersecretion of growth hormone (GH) Acromegaly • Hypersecretion of GH during adulthood • Slowly progressive Mortality: cardiac hypertrophy, hypertension, atherosclerosis, type 2 diabetes mellitus lead to coronary artery disease Malignancies common Giantism • GH hypersecretion in children and adolescents Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Clinical Manifestations of Acromegaly Connective tissue proliferation Enlarged tongue, interstitial edema, increase in the size and function of sebaceous and sweat glands, coarse skin and body hair Bony proliferation Large joint arthropathy Periosteal vertebral growth • Kyphosis Enlargement of facial bones and hands and feet • Protrusion of the lower jaw and forehead • Need for increasingly larger sizes of shoes, hats, rings, and gloves Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Hypersecretion of GH Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Diseases of the Anterior Pituitary Hypersecretion of prolactin Caused by prolactinomas • Most common hormonally active pituitary tumor • In females, increased levels of prolactin cause amenorrhea, galactorrhea, hirsutism, and osteopenia • In males, increased levels of prolactin cause hypogonadism, erectile dysfunction, impaired libido, oligospermia, and diminished ejaculate volume Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Alterations of Thyroid Function Primary Dysfunction or disease of thyroid gland • TH production Secondary Alteration of pituitary TSH production Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Alteration in Thyroid Function Primary Hyperthyroidism, hypothyroidism Thyrotoxicosis Graves' disease • Pretibial myxedema Hyperthyroidism resulting from nodular thyroid disease • Goiter Thyrotoxic crisis Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Thyrotoxicosis (Graves' Disease) Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Alterations of Thyroid Function Hypothyroidism Primary hypothyroidism • Subacute thyroiditis • Autoimmune thyroiditis (Hashimoto disease) • Painless thyroiditis • Postpartum thyroiditis • Myxedema coma Congenital hypothyroidism Thyroid carcinoma Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Hypothyroidism Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Alterations of Parathyroid Function Hyperparathyroidism Primary hyperparathyroidism • Excess secretion of PTH from one or more parathyroid glands • 85% caused by parathyroid adenomas Secondary hyperparathyroidism • Increase in PTH secondary to a chronic disease Renal failure Dietary deficiency of vitamin D, calcium Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Alterations of Parathyroid Function Hyperparathyroidism Hypercalciuria Alkaline urine Hyperphosphaturia • Predisposes to the formation of calcium stones Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Alterations of Parathyroid Function Hypoparathyroidism Abnormally low PTH levels • Depressed serum calcium level • Increased serum phosphate level Usually caused by parathyroid damage in thyroid surgery Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Alterations of Parathyroid Function Hypoparathyroidism clinical signs Hypocalcemia • Lowering of the threshold for nerve and muscle excitation • Muscle spasms; hyperreflexia; tonic-clonic convulsions; laryngeal spasms; death from asphyxiation Phosphate retention Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Diabetes Mellitus Type 1 Type 2 Gestational diabetes Glucose intolerance Fasting, 2 hour post glucose load, A1C Other types Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Type 1 Diabetes Mellitus Demonstrates pancreatic atrophy and loss of beta cells Macrophages, T and B lymphocytes, and natural killer cells are present Two types Immune Nonimmune Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Type 1 Diabetes Mellitus Genetic susceptibility Environmental factors Immunologically mediated destruction of beta cells Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Type 1 Diabetes Mellitus Clinical manifestations Hyperglycemia • 80% to 90% of the function of the insulin-secreting beta cells in the islet of Langerhans is lost Polydipsia, polyuria, polyphagia, weight loss, and fatigue Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Dysfunction of the Pancreas Type 2 diabetes mellitus Affects adults and children Genetic environmental interaction Metabolic syndrome Treatment • Exercise, treatment of obesity, medication Clinical manifestations • Recurrent infections, vision problems, neuropathy Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Diabetes Mellitus Maturity onset diabetes of youth (MODY) Gestational diabetes Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Acute Complications of Diabetes Mellitus Hypoglycemia Diabetic ketoacidosis Usually associated with Type 1 Illness, trauma, surgery, emotions Total body (not serum) potassium deficiency Cerebral edema, especially in children Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Acute Complications of Diabetes Mellitus Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS) Usually associated with Type 2 Higher glucose Less ketosis Severe dehydration and potassium deficit Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Acute Complications of Diabetes Mellitus Somogyi effect Usually associated with Type 1 Hypoglycemia with rebound hyperglycemia Not as common as once thought Dawn phenomenon Early morning glucose elevation without nocturnal hypoglycemia Related to nocturnal growth hormone elevation Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Chronic Complications of Diabetes Mellitus Hyperglycemia and nonenzymatic glycosylation Hyperglycemia and the polyol pathway Sorbitol and fructose increase intracellular osmotic pressure (attracts water, leading to cell injury) Evident in the eye lens, nerves, RBCs Protein kinase C • Enzyme inappropriately activated by hyperglycemia Microvascular disease Retinopathy Diabetic nephropathy Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Diabetic Nephropathy Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 34 Complications of Diabetes Mellitus Macrovascular disease Coronary artery disease • Most common cause of death in persons with type 2 • Prevalence increases with duration of disease Stroke Peripheral arterial disease Diabetic neuropathies Infection Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Diabetic Neuropathy Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Alterations of Adrenal Function Disorders of the adrenal cortex Cushing disease • Excessive anterior pituitary secretion of ACTH Cushing syndrome • Excessive level of cortisol, regardless of cause Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Cushing Disease Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Alterations of Adrenal Function Disorders of the adrenal cortex Hyperaldosteronism • Primary hyperaldosteronism (Conn disease) • Secondary hyperaldosteronism Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Primary Hyperaldosteronism Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Alterations of Adrenal Function Disorders of the adrenal cortex Adrenocortical hypofunction • Primary adrenal insufficiency (Addison disease) Idiopathic Addison disease • Secondary hypocortisolism Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Alterations of Adrenal Function Disorders of the adrenal cortex Hypersecretion of adrenal androgens and estrogens • Feminization • Virilization Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Virilization Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 Alterations of Adrenal Function Disorders of the adrenal medulla Adrenal medulla hyperfunction • Caused by tumors derived from the chromaffin cells of the adrenal medulla Pheochromocytomas • Secrete catecholamines on a continuous or episodic basis Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Pheochromocytoma Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 45
