Hormones Patho

Copyright Information

• Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc.

• Chapter 22: Alterations of Hormonal Regulation

• Copyright © 2019, Elsevier Inc. All rights reserved.

Overview of Hormonal Alterations

• Main Focus Areas:

  • Mechanisms of Hormonal Alterations

  • Diseases of the Posterior Pituitary

  • Diseases of the Anterior Pituitary

  • Alterations in Thyroid Function

  • Alterations in Parathyroid Function

  • Type I and Type 2 Diabetes Mellitus

  • Alterations of Adrenal Function

Mechanisms of Hormonal Alterations

• Causes of Hormonal Imbalance:

  • Too much or too little hormone production

  • Failure of feedback systems:

  • May fail to function properly

  • May respond to inappropriate signals

  • Dysfunction of an endocrine gland:

  • Inability to produce or obtain adequate hormone precursors

  • Inability to convert precursors to active hormone

  • Excessive or inadequate hormone production

Hormonal Inactivation and Dysregulation

• Altered hormone inactivation or degradation: Hormones may be degraded or inactivated improperly leading to imbalances.

• Ectopic hormone release:

  • Hormones secreted from nonendocrine sites

  • Autonomous production without feedback mechanisms

Target Cell Dysfunction

• Failure of Target Cell Response (Hormone Insensitivity):

  • Receptor-associated disorders:

  • Decrease in the number of receptors

  • Impaired receptor function

  • Presence of antibodies against specific receptors

  • Antibodies that mimic hormone action

  • Unusual expression of receptor function

  • Intracellular disorders:

  • Inadequate synthesis of a second messenger; e.g., cyclic adenosine monophosphate (cAMP)

  • Failure of the target cell to produce anticipated response to hormones

    • Faulty response to hormone-receptor binding

    • Failure to generate required second messenger

    • Abnormal response to second messenger

Diseases of the Posterior Pituitary

• Key Functions of Antidiuretic Hormone (ADH):

  • Involves water balance in the body

• Examples of Diseases:

  • Hyperfunction:

  • Syndrome of inappropriate antidiuretic hormone (SIADH) secretion

  • Hypofunction:

  • Diabetes insipidus:

    • Types:

    • Neurogenic: insufficient amounts of ADH

    • Nephrogenic: renal insensitivity to ADH

    • Dipsogenic: excessive fluid intake lowers plasma osmolarity

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

• Characteristics:

  • Levels of ADH are abnormally high

  • Commonly caused by ectopic secretion, surgery, or certain cancers

  • Leads to water retention due to increased permeability in renal collecting ducts

• Diagnosis: Ensuring normal renal, adrenal, and thyroid functions

• Clinical Manifestations:

  • Hyponatremia: sodium <135 mEq/L

  • Hypoosmolality: <280 mOsm/kg

  • Urine hyperosmolality: higher than serum levels

  • Hypervolemia and weight gain

  • Risk of neurologic damage if sodium levels drop below 110–115 mEq/L

• Treatment:

  • Address underlying issues, restrict fluids (800-1000 mL/day), administer hypertonic saline for severe hyponatremia

  • Use medications like Vaptans or demeclocycline for chronic cases

Diabetes Insipidus

• Characteristics: Inadequate ADH leads to polyuria and polydipsia

  • Inability to concentrate urine appropriately

• Clinical Types:

  • Neurogenic: Insufficient ADH levels

  • Nephrogenic: Renal collecting tubules’ insensitivity to ADH

  • Dipsogenic: Excessive fluid intake reducing plasma osmolarity below the threshold for ADH secretion

• Clinical Manifestations:

  • Polyuria, nocturia, constant thirst

  • Low urine specific gravity: <1.010

  • Low urine osmolality (<200 mOsmL/kg)

  • Hypernatremia and diuresis

• Treatment:

  • Neurogenic: Synthetic vasopressin analog, desmopressin acetate (DDAVP)

  • Nephrogenic: Correct underlying disorders, use diuretics and manage electrolytes

  • Dipsogenic: Effective management of fluid intake

Diseases of the Anterior Pituitary

• Functioning Hormones:

  • Growth hormone, Prolactin, ACTH, TSH, LH, and FSH

• Examples of Diseases:

  • Hyperfunction: Hyperpituitarism, Acromegaly, Prolactinoma

  • Hypofunction: Hypopituitarism, Panhypopituitarism (all hormones affected)

• Common Causes of Hypopituitarism:

  • Inadequate release of hypothalamic-releasing hormones

  • Damage to stalk or pituitary gland

  • Infarction, tumors, or surgical removal

Acromegaly & Prolactinoma

• Acromegaly:

  • Due to hypersecretion of growth hormone in adults leading to progressive changes

  • Can result in cardiovascular complications and diabetes

• Prolactinoma:

  • Most common hormonally active tumor

  • Symptoms differ by sex; in women causes amenorrhea, galactorrhea; in men, erectile dysfunction and infertility

  • Treatment: Medications like cabergoline, surgery, and possibly other therapies

Alterations of Thyroid Function

• Hyperfunction and Hypofunction:

  • Hyperthyroidism: Graves disease, toxic multinodular goiter, and thyroid storm

  • Hypothyroidism: Hashimoto disease, congenital hypothyroidism

  • Diagnosing through clinical symptoms, lab assessments including T3, T4 and TSH

Differences Between Hyperthyroidism and Hypothyroidism

• Hyperfunction Symptoms:

  • Thin hair, exophthalmos, normal or enlarged thyroid, tachycardia

  • Muscle weakness, warm skin, pretibial myxedema

• Hypofunction Symptoms:

  • Coarse hair, puffy face, low basal metabolic rate, bradycardia

  • Myxedema and potential myxedema coma if untreated

Alterations in Parathyroid Function

• Hyperparathyroidism:

  • Caused primarily by adenomas, results in hypercalcemia

• Hypoparathyroidism:

  • Low PTH levels lead to hypocalcemia and associated symptoms

  • Results from parathyroid damage commonly due to surgery or autoimmunity

Diabetes Mellitus

• Types:

  • Type 1 Diabetes Mellitus

  • Type 2 Diabetes Mellitus

  • Other specific types and gestational diabetes

• Diagnosis Criteria:

  • Glycosylated hemoglobin (HgA1C), FPG, OGTT

Type 1 Diabetes Mellitus

• Pathophysiology: Autoimmune destruction of beta cells in the pancreas results in insulin deficiency, showing symptoms like fatigue, polyuria, and weight loss

• Genetic Factors: Involvement of environmental factors, viral infections, and family history

• Treatment Strategies: Including insulin therapy and lifestyle planning

Type 2 Diabetes Mellitus

• Pathophysiology: Characterized by insulin resistance and progressive beta-cell dysfunction leading to hyperglycemia

• Risk Factors: Age, obesity, genetics, sedentary lifestyle

• Key Manifestations: Fatigue, pruritus, recurrent infections, visual disturbances

• Management: Lifestyle changes, medications, and in some cases, bariatric surgery

Acute Complications of Diabetes Mellitus

• Hypoglycemia: Tachycardia, diaphoresis, and potential loss of consciousness

• Diabetic Ketoacidosis (DKA): Presents with high blood glucose, acidosis, and ketone presence

• Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS): Extreme hyperglycemia without significant ketosis

• Somogyi effect and Dawn phenomenon: Patterns of variable glucose levels during the night

Chronic Complications of Diabetes Mellitus

• Microvascular Diseases: Diabetic retinopathy, nephropathy, neuropathies

• Macrovascular Diseases: Coronary artery disease, myocardial infarction, stroke

• Infection Risks: Increased susceptibility to infections due to multiple factors including altered immune function

Adrenal Function Alterations

• Cushing Disease and Syndrome:

  • Chronic excessive cortisol levels

• Addison Disease:

  • Primary adrenal insufficiency with low cortisol levels and high ACTH

• Hyperandrogenism and Hyperaldosteronism:

  • Results in various clinical features, including virilization and electrolyte imbalances

• Pheochromocytoma:

  • Tumors that secrete catecholamines, presenting with hypertension and other symptoms

Summary

• Understanding hormonal alterations is critical for diagnosing and treating endocrine diseases.

• Recognizing the symptoms and pathophysiology can lead to effective management of conditions leading to improved patient outcomes.