TEST 4: Endocrine Disorders Flashcards
Primary Thyroid disease
Causes
(Lecture, p. 697)
-MOST COMMON thyroid disorder
Primary:
-iodine deficiency (common outside US)
-autoimmune thyroiditis:
ie Hashimoto and lymphocytic thyroiditis with inflammatory destruction of thyroid gland (circulating antibodies and t lymphocytes, genetic predisposition, manifestation with goiter)
-Postpartum thyroiditis (related to hashimotos, onset 6-12 months postpartum, usually resolves)
-congenital hypothyroid= absent thyroid tissue (results in absent thyroxine—> impaired neuro development, want to screen for in newborns)
-thyroid carcinoma: risk from ionizing radiation
-iatrogenic: ablation or removal of gland
Secondary thyroid disease
(Lecture, p.697)
-Gland itself works but function is impaired
-Pituitary failure to synthesize TSH or respond to TRH (caused by either pituitary tumors or TBI/SAH)
Side note:
Can also be subclinical (though not secondary): typically a post viral process that results in autoimmune injury to thyroid
Hyperthyroidism (Thyrotoxicosis)
(Lecture, p. 694)
Thyrotoxicosis: A condition that results in elevated thyroid hormone from ANY cause
Primary & Graves
-INCREASED T3 and T4, DECREASED TSH
Graves’ disease:
-Autoimmune (type 2 hypersensitivity)
-Genetic/ environmental etiology
-Common manifestations: exophthalmos and pretibial myxedema
Nodular disease (secondary)
-Thyroid gland increases in size in response to increased TSH
–goiter
-Benign or cancerous forms
-Lack exophthalmos and pretibial myxedema
Thyroid crisis: Myxedema Coma
Definition
Symptoms
Treatment
(Lecture, p.697)
Critical LOW
- Myxedema Coma:
-Decreased LOC associated with severe HYPOthyroidism
-Usually preceded by: infection, discontinuation of thyroid meds, overuse narcotics/ sedatives (patients with co morbidities UTI, CHF, CVA at increased risk)
-Manifestations: hypothermia, hypo ventilation, hypotension, hypoglycemia, lactic acidosis, coma
-Tx: thyroid hormone replacement
Thyroid crisis: Thyrotoxic crisis
(Lecture, p. 697)
Thyrotoxic crisis:
-Rare, dangerous ACUTE HYPERthyroid
-Often occurs in people with hyperthyroid that is undiagnosed or only partially treated when exposed to a stressor
-Sudden release of T4 and T3 that exceeds metabolic demand
-Manifestations: hyperthermia, tachycardia, high output HF, agitation, delirium, n/v
-Tx: thyroid blocking hormones and supportive treatment
Hyperaldoateronism
(Lecture, p.716)
-Excess aldosterone secretion by adrenal cortex
-Typically the result of adrenal carcinoma (primary)
-Secondarily the result of dysfunction of RAS system
-Manifests with: hypokalemia, insulin resistance, LV remodeling with HTN and hypervolemia
Cushing Syndrome
(Lecture, p. 715)
-AKA “chronic hypercortisolism”
-Occurs from increased cortisol (pituitary adenoma, increased ACTH, steroids)
-2 responses: loss of circadian rhythm of ACTH and cortisol or inability to increase ACTH in response to stress
-Also at risk for developing a Cushing like syndrome (people on chronic steroids)
-Manifestations: weight gain from increased adipose tissue, insulin resistance, protein wasting
-Treatment: meds, radiation, surgery
-hallmark: buffalo hump/ moon face
Addison’s disease
(Lecture, p. 717)
-AKA “primary adrenal insufficiency”
-Occurs from decreased cortisol and aldosterone synthesis, increased ACTH
-Primary = autoimmune destruction of the adrenal cortex (genetic)
-Secondary = prolonged suppression of cortisol secretion (glucocorticoids)
-Treatment: lifetime steroid replacement
Diabetes Mellitus Overview
(Lecture, p. 702)
A group of metabolic diseases characterized by hyperglycemia resulting from:
-deficits in insulin secretion and/or deficit in insulin action
-Type 1, 2, Gestational, other (steroid induced)
Diabetics Mellitus Diagnosis
(Lecture, p. 702)
-Hgb A1C > 6.5 %
-Fasting glucose > 126 mg/ dl
-2 hour postprandial glucose > 200 mg/dl
Type 1 Diabetes Mellitus
(Lecture, p. 702)
-Loss of beta cells= loss of insulin production
-Not typical before 6 months, peak diagnosis is 12 years old
-Type 1B: not autoimmune—> secondary (pancreatic injury that is not autoimmune ie cancer, trauma)
-Type 1A: autoimmune,
thought to be due to:
-Genetics + environment
-Alpha and beta cell (insulin and amylin) function is abnormal to varying Degrees
-Excess glucagon caused hyperglycemia and hyperketonemia
-Immune mediated T cell destruction of beta cells (lymphocytes and macrophages infiltrate islet cells, or possibly in response to a virus)
Type 2 Diabetes Mellitus
(Lecture, p. 705)
-Thought to be due to genetic and environment factors
-Risk factors: obesity, age, HTN, inactivity, family history
-those with Metabolic syndrome: increased waist circumference, elevated triglycerides, low HDL, HTN, fasting glucose > 100
Pathophysiology:
-decreased insulin secretion
-Increased resistance (insulin sensitive tissues fail to respond to circulating insulin) likely Related to—>
insulin molecule abnormalities, insulin antagonists, down regulated receptors, altered glucose transport proteins, decreased activation of post receptor kinase
5 ways obesity contributes to insulin resistance
(Lecture)
- Adipokines (leptin and adiponectin) are produced by adipose tissue and obesity changes the levels—> decreases insulin synthesis and increases insulin resistance
- Elevated free fatty acids increase triglycerides and cholesterol—> disrupts intracellular insulin signaling, decreased tissue response to insulin +pro- inflammatory
- Obesity causes release of inflammatory cytokines—> induces insulin resistance and contributes to fatty liver, dyslipidemia, and atherosclerosis
- Obesity alters oxidative phosphorylation in cellular mitochondria—> causing insulin resistance and changes in energy production
- Obesity associated with hyperinsulinemia and decreased insulin receptors
Patho of type 2 diabetes
(Lecture, p.706)
-Beta cell dysfunction (decrease in weight and number) —>
glucagon increases (pancreatic alpha cells are less responsive to glucose inhibition which causes increased gluconeogensis and glycogenolysis) —>
amylin decreases (loss of satiety and increased glucagon production) —>
GI hormones ghrelin and incretins decrease (causing decreased in insulin response to food and increased insulin resistance)
Acute complications of DM-
Ketoacidosis
(Lecture, p. 710)
-Related to a deficiency of insulin and increase in the levels of insulin counterregulatory hormones (catecholamines, cortisol, glucagon, GH)
-More common in type 1
-With insulin deficiency—> lipolysis is enhanced and there’s an increase in the amount of fatty acids delivered to the liver—> consequences is increased gluconeogensis, which cause hyperglycemia and production of ketone bodies at a rate that exceeds use—> accumulation causes a drop in pH causing metabolic acidosis
-S/s: kussmaul respirations, hyperventilation, dizziness, CNS depression, ketonuria, n/v, thirst
-Tx: fluids, insulin, electrolyte replacement
Acute complications of dm:
Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)
711
-Characterized by a lesser degree of insulin deficiency, therefore preventing lipolysis and the production of ketones.
-hyperglycemia is more profound here than in DKA
-Hallmark: extremely high blood sugar with no acidosis associated
-Manifeststions: profound dehydration, loss of electrolytes, neuro changes
-Tx: fluid, insulin electrolytes
Acute complication of DM:
Hypoglycemia
(Lecture, p.710)
-Glucose < 47 in first 48 hours of life or <70 in adults and kids
Causes:
Exogenous: medication, alcohol, exercise
Endogenous: pancreas tumor, inherited disorder
Functional: hyperalimentation, liver disease
Manifestations: AMS, tachycardia, palpitations, diaphoresis, tremors
Brain needs glucose= this is emergent
Chronic hyperglycemia consequences
(Lecture, p. 711, AO)
-Microvascular disease in small blood vessels (retinopathy, nephropathy, neuropathy)
-Macrovascular disease in large blood vessels (cardiovascular disease, stroke, PVD)
-Infection
Patho of the chronic complications of DM
(Lecture)
- Oxidative stress increases reactive oxygen species that cause cell damage
- Polyps pathways (alternative pathway for glucose metabolism that when activated sorbitol is released which increases intracellular osmotic pressure and increase glutathione which results in oxidative injury to the blood vessels
- Protein Kinase C release —> increases insulin resistance, cytokine production, angiogenesis—> causes microvascular complications
- Glycation—> glucose binds irreversibly to collagen, proteins in RBC, vessel walls and interstitium—> advanced glucation end products with abnormal cell proliferation and inflammatory changes
Retinopathy complication of DM
(Lecture, p. 711)
-Microvascular disease
-Happens as a result of damage to blood vessels, vasoconstriction, platelet aggregation, Hypoxemia
- Non-proliferative: thickening of retinal capillary membrane and increased membrane permeability with vein dilation and micro aneurysm formation
- Pre-proliferative: retinal ischemia with areas of poor perfusion and infarcts
- Proliferative: angiogenesis and fibrous tissue formation in the retina or optic disc
-Macular edema, glaucoma, and cataract risk increased
Nephropathy complication of DM
(Lecture, p. 712)
-Microvascular
-Results from hyperglycemia activating the polyol pathway, protein Kinase C and Inflammation —> causing advanced glycation end products, which results in:
Renal glomerular changes:
-Glomerular enlargement, glomerular basement membrane thickening
-Diffuse nodular glomerulosclerosis which causes a loss of podocytes, decreased GFR
GEM- most common causes of chronic kidney disease
Neuropathy complications of DM
(Lecture, p.713)
-Microvascular disease
-Results from metabolic and vascular changes related to chronic hyperglcemia
-Inflammation, ischemia, oxidative stress, advanced glycation, increased polyols—> dymyelination, nerve degeneration, delayed conduction
-Starts with Schwann cell degeneration in peripheral sensory nerves (can include spinal cord nerve and posterior root ganglia degeneration too)
-At increased risk for infections with all chronic complications
Macrovascular complications of DM
(Lecture, p. 713)
- Cardiovascular disease (HTN, CAD, MI)
- Stroke (ischemic/ lacunar increased risk)
- PAD (atherosclerosis of lower extremities with increased risk for
Ulcers, gangrene, BTK amputation)
Autoimmune thyroiditis
What is it
(AO)
-Includes Hashimoto’s
-Group of disorders where body’s immune system attacks thyroid gland
-Can cause both hypo and hyperthyroid
Subclinical thyroid disease
(AO)
-Thyroid function is mildly impaired but doesn’t yet cause noticeable symptoms
-Not considered pre- disease but spectrum of disease
-Can progress or resolve over time
General underlying patho of chronic DM complications
(AO)
-Production of reactive oxygen species, oxidative stress, and cellular death
-Polyol pathway: a metabolic route that converts excess glucose into sorbitol and fructose (consumes NADPH which is crucial for cellular functions)
-Glucose induced activation of protein kinase C: multiple downstream effects on vascularity and cell function
-Glycation and advanced glycation end products: when glucose non- enzymatically binds to proteins, lipids, nucleic acids to form AGEs leading to functional impairment and development of chronic disease
Hypoaldosteronism
(P.718)
-Caused by adrenal insufficiency (Addison’s disease)
