Alterations of Hormonal Regulation Chapter 21 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 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. 3 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. 4 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 Failure to generate required second messenger Abnormal response to the second messenger Abnormal response to the second messenger

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Alterations of the Hypothalamic-Pituitary System

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 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 Related to enhanced renal water retention Hyponatremia Hyponatremia Hypoosmolarity Hypoosmolarity

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 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 Insufficient amounts of ADH  Nephrogenic Inadequate response to ADH Inadequate response to ADH

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Diseases of the Anterior Pituitary  Pituitary is vascular and therefore vulnerable to ischemia and infarction  Hypopituitarism  Pituitary infarction Sheehan syndrome Sheehan syndrome Hemorrhage Hemorrhage Shock Shock  Others: head trauma, infections, and tumors

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Diseases of the Anterior Pituitary  Hypopituitarism  Panhypopituitarism (all hormones absent) ACTH deficiency ACTH deficiency TSH deficiency TSH deficiency FSH and LH deficiency FSH and LH deficiency GH deficiency GH deficiency  Glucose intolerance

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Diseases of the Anterior Pituitary  Hyperpituitarism  Commonly due to a benign, slow-growing pituitary adenoma  Manifestations Headache and fatigue Headache and fatigue Visual changes Visual changes Hyposecretion of neighboring anterior pituitary hormones Hyposecretion of neighboring anterior pituitary hormones

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Diseases of the Anterior Pituitary  Hypersecretion of growth hormone (GH)  Acromegaly Hypersecretion of GH during adulthood Hypersecretion of GH during adulthood Slowly progressive 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 GH hypersecretion in children and adolescents

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 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 Kyphosis  Enlargement of facial bones and hands and feet Protrusion of the lower jaw and forehead Protrusion of the lower jaw and forehead Need for increasingly larger sizes of shoes, hats, rings, and gloves 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. 13 Hypersecretion of GH

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Diseases of the Anterior Pituitary  Hypersecretion of prolactin  Caused by prolactinomas Most common hormonally active pituitary tumor Most common hormonally active pituitary tumor In females, increased levels of prolactin cause amenorrhea, galactorrhea, hirsutism, and osteopenia 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 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. 15 Alterations of Thyroid Function  Primary  Dysfunction or disease of thyroid gland TH production TH production  Secondary  Alteration of pituitary TSH production

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Alteration in Thyroid Function  Primary  Hyperthyroidism, hypothyroidism  Thyrotoxicosis  Graves' disease Pretibial myxedema Pretibial myxedema  Hyperthyroidism resulting from nodular thyroid disease Goiter Goiter  Thyrotoxic crisis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Thyrotoxicosis (Graves' Disease)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Alterations of Thyroid Function  Hypothyroidism  Primary hypothyroidism Subacute thyroiditis Subacute thyroiditis Autoimmune thyroiditis (Hashimoto disease) Autoimmune thyroiditis (Hashimoto disease) Painless thyroiditis Painless thyroiditis Postpartum thyroiditis Postpartum thyroiditis Myxedema coma Myxedema coma  Congenital hypothyroidism  Thyroid carcinoma

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Hypothyroidism

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Alterations of Parathyroid Function  Hyperparathyroidism  Primary hyperparathyroidism Excess secretion of PTH from one or more parathyroid glands Excess secretion of PTH from one or more parathyroid glands 85% caused by parathyroid adenomas 85% caused by parathyroid adenomas  Secondary hyperparathyroidism Increase in PTH secondary to a chronic disease 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. 21 Alterations of Parathyroid Function  Hyperparathyroidism  Hypercalciuria  Alkaline urine  Hyperphosphaturia Predisposes to the formation of calcium stones Predisposes to the formation of calcium stones

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Alterations of Parathyroid Function  Hypoparathyroidism  Abnormally low PTH levels Depressed serum calcium level Depressed serum calcium level Increased serum phosphate 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. 23 Alterations of Parathyroid Function  Hypoparathyroidism clinical signs  Hypocalcemia Lowering of the threshold for nerve and muscle excitation Lowering of the threshold for nerve and muscle excitation Muscle spasms; hyperreflexia; tonic-clonic convulsions; laryngeal spasms; death from asphyxiation 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. 24 Diabetes Mellitus  Type 1  Type 2  Gestational diabetes  Glucose intolerance  Fasting, 2 hour post glucose load, A 1 C  Other types

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 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. 26 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. 27 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 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. 28 Dysfunction of the Pancreas  Type 2 diabetes mellitus  Affects adults and children  Genetic environmental interaction  Metabolic syndrome  Treatment Exercise, treatment of obesity, medication Exercise, treatment of obesity, medication  Clinical manifestations Recurrent infections, vision problems, neuropathy Recurrent infections, vision problems, neuropathy

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 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. 30 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. 31 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. 32 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. 33 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 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. 34 Diabetic Nephropathy

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Complications of Diabetes Mellitus  Macrovascular disease  Coronary artery disease Most common cause of death in persons with type 2 Most common cause of death in persons with type 2 Prevalence increases with duration of disease 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. 36 Diabetic Neuropathy

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Alterations of Adrenal Function  Disorders of the adrenal cortex  Cushing disease Excessive anterior pituitary secretion of ACTH Excessive anterior pituitary secretion of ACTH  Cushing syndrome Excessive level of cortisol, regardless of cause Excessive level of cortisol, regardless of cause

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Cushing Disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Alterations of Adrenal Function  Disorders of the adrenal cortex  Hyperaldosteronism Primary hyperaldosteronism (Conn disease) Primary hyperaldosteronism (Conn disease) Secondary hyperaldosteronism Secondary hyperaldosteronism

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Primary Hyperaldosteronism

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  Adrenocortical hypofunction Primary adrenal insufficiency (Addison disease) Primary adrenal insufficiency (Addison disease)  Idiopathic Addison disease Secondary hypocortisolism Secondary hypocortisolism

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Alterations of Adrenal Function  Disorders of the adrenal cortex  Hypersecretion of adrenal androgens and estrogens Feminization Feminization Virilization Virilization

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 Virilization

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Alterations of Adrenal Function  Disorders of the adrenal medulla  Adrenal medulla hyperfunction Caused by tumors derived from the chromaffin cells of the adrenal medulla Caused by tumors derived from the chromaffin cells of the adrenal medulla  Pheochromocytomas Secrete catecholamines on a continuous or episodic basis Secrete catecholamines on a continuous or episodic basis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 45 Pheochromocytoma