Pathophysiology Ch. 40 & 41

Adrenal: Cushing Syndrome (Hypercortisolism)- 3 Forms

(1) Pituitary Form: Excessive production of ACTH by a tumor on the pituitary gland (2) Adrenal Form: Caused by benign or malignant adrenal tumor (3) Ectopic Cushing Syndrome: Caused by a nonpituitary ACTH-secreting tumor

Primary adrenal insufficiency (Addison's disease)

- Autoimmune destruction of adrenal cortex - Glucocorticoid, Mineralocorticoid, and Androgen Abnormalities - Hyperkalemia, Hyponatremia, Hypoglycemia - Low fluid due to Na loss resulting in Hypotension, weakness, lethargy - Decreased immune function and inflammatory abilities - Lifetime hormone replacement

Congenital Adrenal Hyperplasia/Androgenital Syndrome

- Autosomal Recessive Trait - Deficiency in enzymes needed to synthesize cortisol - Results in high levels of ACTH and overproduction of adrenal androgens - Affects both sexes (Females have virilized genitalia)(Boys seldom diagnosed at birth unless enlarged genitalia)

Diagnostic Testing for Endocrine Disorders

- Blood Tests (looking for blood hormone levels) - Urine Tests (looking for hormones or hormone metabolites) - Genetic Tests - Imaging Tests (Isotropic Imaging, MRI, CT, Unltrasound, PET, DEXA) - Fine Needle Aspiration

GH or Somatotropin is for:

- Bone and cartilage growth (stimulates the liver to produce IGFs resulting in bone and cartilage growth) - visceral and endocrine organ growth - skeletal and cardiac muscle growth - skin and connective tissue growth

Cushing Syndrome signs and symptoms

- Buffalo Hump - Moon Face - stretch marks -weak skin - osteoporosis - increased facial hair in women

Hypopituitarism signs and symptoms

- Chronically unfit - weakness - fatigue - loss of appetite - impairment of sexual function - cold intolerance

Congenital Hypothyroidism

- Cretinism: condition of abnormal mental and physical development resulting from a deficiency of thyroid hormone in fetal or early life, typically characterized by intellectual disability, small stature, and thickening of the facial features - Mental Retardation - Impaired Physical Growth

Signs and Symptoms of Acromegaly

- Enlarged bones of hands and feet - Broad, Bulbous nose - Protruding lower Jaw - Slanting Forehead - Splayed Teeth - Deepening of voice - Development of bronchitis - Vertebral changes leading to kyphosis or hunchback - Glucose Intolerance leading to Diabetes Mellitus

"Tall" GH Excess Disorders in Children

- Genetic: Marfan Syndrome and Klinefelter (XXY) Syndrome - Excess GH: Gigantism

Causes of Hyperthyroidism

- Graves Disease (most Common): ----Triad of symptoms: Ophthalmopathy (bulging eyes), Goiter, dermopathy (myxedema) - Other Causes: Multinodal Goiter, Adenoma of Thyroid, Thyroiditis

"Short" disorders in children

- Idiopathic short stature (cause unknown; just short) - Psychosocial Dwarfism (caused from emotional deprivation) - GH and Insulin-like growth factor deficiency (idiopathic cause or pituitary tumor / agenesis) - Classic GH deficiency

Endocrine Disorders

- Impact MANY systems - Present as HYPO or HYPER function - Can be Primary, Secondary, or Tertiary

Thyroid Controls:

- Metabolism -Protein Synthesis -Growth and development in children (mental and sexual)

Responsiveness of a target cell depends on:

- Number of cell receptors present - Affinity of those receptors for binding

Tertiary Disorders

- Result from hypothalamic dysfunction - Both the pituitary and target organ are understimulated

Thyroid Gland

- Secretes T4 (90%) and T3 (10%) - Regulated by the Hypothalamic- Pituitary- Thyroid Feedback System - Affects function of many organs

Acquired Hypothyroidism

- Slowed Metabolism - Myxedema: swelling of the skin and underlying tissues giving a waxy consistency, typical of patients with underactive thyroid glands. - Primary hypothyroidism most common - Hashimoto Thyroiditis: Autoimmune Disorder; Most common cause; predominantly a disease of WOMEN

Hypopituitarism

- decreased secretion of pituitary hormones - Loss usually gradual and follows classic course: GH, LH, FSH secretions followed by deficiencies in TSH, then ACTH, then Prolactin - Treatment is replacement therapy

Classification of hormones

- endocrine - paracrine - autocrine - intracrine - neuroendocrine

diagnosing GH deficiency disorder - short stature

- physical exam - blood test - hormonal testing - bone x-rays - MRI of hypothalamic-pituitary area

"Tall" GH excess Disorders in Adults

-Excess GH: Acromegaly (Cannot grow taller; soft tissues continue to grow) - GH secreting adenomas: most common

Thyroid effects Neuromuscular

-Increased thyroid hormone cause skeletal muscles to react more vigorously and decreased thyroid hormone causes skeletal muscles to react sluggishly. -Hyperthyroidism may cause overactivity of sympathetic Nervous System

Hypothyroidism treatment

-Lifelong thyroid hormone replacement therapy (usually T4) -"go low and go slow" approach

Pituitary Tumors

-Primary: pituitary normal, target abnormal -Secondary: Target normal, pituitary abnormal - Functional: Secreting hormones - Non-Functional: NOT secreting hormones

4 Categories of Hormones

1- Amines and Amino Acids 2- Peptides proteins and glycoproteins 3- Steroids 4- Fatty Acids

Thyroid Storm

A relatively rare, life-threatening condition caused by exaggerated hyperthyroidism. High Fever Extreme Cardiovascular Effects- tachy., CHF, angina Severe CNS Effects- delirium, aggitation, restlessness

Posterior Pituitary Hormones

ADH, Oxytocin

Negative Feedback Signals

Body sensors detect a change in hormone level and adjust hormone secretion so that body levels are maintained within an appropriate range. When hormone levels decrease, changes are initiated to increase levels.

Endocrine Hypofunction

Caused by: - Absence or impaired development of a gland - Deficiency of an enzyme needed for hormone synthesis - Gland destroyed by low blood flow, infection, inflammation, autoimmune response, neoplastic growth - Decline in function due to AGING - Atrophy due to drug therapy or unknown reason

Pituitary Gland

Connected to the floor of the hypothalamus by pituitary stalk

Downregulation

Decrease in receptor number in response to high concentration of hormone

Hypothalamic Hormones

Either (1) Releasing Hormones or (2) Inhibiting Hormones (CRH, TRH, GHRH, GnRH, Somatostatin, Dopamine) *pg. 1035

Anterior Pituitary Hormones

GH, ACTH, TSH, FSH, LH, Prolactin (pg.1035)

Thyroid effects Cardiovascular

High levels of thyroid hormones increase metabolic rate and therefore increases blood volume, cardiac output, and ventilation.

Thyroid effects GI

Higher metabolic rates increase GI motility and usually cause diarrhea, increased appetite and food intake, weight loss

Mechanism of Action

Hormones produce effects through high-affinity receptors. Receptors can be located on: 1- Cell Surface 2- Intracellular Receptor

Inhibiting Hormones

Hypothalamic hormones that can suppress secretion of hormones by the anterior pituitary

Releasing hormones

Hypothalamic hormones that stimulate the release of hormones from the anterior pituitary

Hypothalamus

Located centrally in the brain and coordinates endocrine, behavioral, and autonomic system function

Metabolism and Elimination

Peptide- degrade in blood and excreted by kidneys and liver Steroid- most are bound and are inactive in bound form

Positive Feedback Signals

Rising levels of hormones cause another gland to release a hormone that is stimulating to the first.

Adrenal Gland

Small bilateral structures that lie retroperitoneally at the apex of each kidney -Medulla: inner portion; secretes epinephrine & norepinephrine (not necessary for life) - Cortex: Bulk of Gland; secretes more than 30 hormones (Aldosterone, Coritsol, Androgens) (CRITICAL for life)

Transport of Hormones

Some circulate freely in bloodstream as free/unbound molecules or attached to protein carriers. Peptides do not require a transport carrier. Steroid and Thyroid do require a transport.

Synthesis of Hormones

Synthesized and stored in vesicles in the cytoplasm of the endocrine cell until secretion required (This does NOT include Cholesterol based hormones)

Cholesterol Based Hormones

Synthesized in smooth ER and leave cell as soon as they're synthesized

Hypothalamic-Pituitary Regulation

The hypothalamus and the pituitary form a functional unit that controls the activities of several endocrine glands leading to a wide range of physiologic functions

Cell Surface Receptors

Used by Peptides and Catecholamines b/c they're water-soluble and cannot cross the lipid cellular membrane

Intracellular Receptors

Used by Steroid and Thyroid hormones b/c they're lipid-soluble and can pass freely through the cell membrane

Endocrine System

Uses chemical substances called hormones to regulate and integrate body functions

Endocrine Hyperfunction

Usually due to excessive hormone production. Caused by: excessive stimulation or hormone producing tumor.

Autocrine

a hormone produces a biologic effect on the same cell that produced it (ex: release of insulin from pancreas inhibits release of more insulin)

Intracrine

a hormone that is synthesized and acts intracellularly in the same cell

Amines and Amino Acids

ex: Epinephrine, Dopamine, Thyroid Hormone

Steroid Hormones

ex: Estrogen, Aldosterone, Testosterone

Peptide Hormones

ex: Insulin, Glucagon, FSH, LH, TRH

Fatty Acids

ex: Prostaglandins, Leukotrienes

Hormones

highly specialized molecules that are produced by endocrine cells that exert their actions on specific target cells

Paracrine

hormones and hormone-like substances never enter the bloodstream, but instead act locally in the vicinity in which they are released (ex: sex steroids on the ovary)

Upregulation

increase in receptor number in response to low concentration of hormone

Primary Disorders

originate in the target gland responsible for producing the hormone

Endocrine Glands

pituitary, thyroid, adrenal, and pancreas

Neuroendocrine

the hormone is produced and released from neurons and then travels through the blood to exert effects on target cells in the body (ex: ADH and epinephrine)

Secondary Disorders

the target gland is essentially normal, but it not producing appropriate levels of hormones b/c it is not receiving appropriate stimulation from pituitary gland.

Endocrine

when a hormone is released into circulation and then travels in the blood to produce a biologic effect on distant target cells