TEST 4: Endocrine Disorders

Question 1

Primary Thyroid disease
Causes
(Lecture, p. 697)

Answer 1

-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

Question 2

Secondary thyroid disease
(Lecture, p.697)

Answer 2

-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

Question 3

Hyperthyroidism (Thyrotoxicosis)
(Lecture, p. 694)

Answer 3

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

Question 4

Thyroid crisis: Myxedema Coma
Definition
Symptoms
Treatment
(Lecture, p.697)

Answer 4

Critical LOW

1. 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

Question 5

Thyroid crisis: Thyrotoxic crisis
(Lecture, p. 697)

Answer 5

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

Question 6

Hyperaldoateronism
(Lecture, p.716)

Answer 6

-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

Question 7

Cushing Syndrome
(Lecture, p. 715)

Answer 7

-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

Question 8

Addison’s disease
(Lecture, p. 717)

Answer 8

-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

Question 9

Diabetes Mellitus Overview
(Lecture, p. 702)

Answer 9

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)

Question 10

Diabetics Mellitus Diagnosis
(Lecture, p. 702)

Answer 10

-Hgb A1C > 6.5 %
-Fasting glucose > 126 mg/ dl
-2 hour postprandial glucose > 200 mg/dl

Question 11

Type 1 Diabetes Mellitus
(Lecture, p. 702)

Answer 11

-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)

Question 12

Type 2 Diabetes Mellitus
(Lecture, p. 705)

Answer 12

-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

Question 13

5 ways obesity contributes to insulin resistance
(Lecture)

Answer 13

1. Adipokines (leptin and adiponectin) are produced by adipose tissue and obesity changes the levels—> decreases insulin synthesis and increases insulin resistance
2. Elevated free fatty acids increase triglycerides and cholesterol—> disrupts intracellular insulin signaling, decreased tissue response to insulin +pro- inflammatory
3. Obesity causes release of inflammatory cytokines—> induces insulin resistance and contributes to fatty liver, dyslipidemia, and atherosclerosis
4. Obesity alters oxidative phosphorylation in cellular mitochondria—> causing insulin resistance and changes in energy production
5. Obesity associated with hyperinsulinemia and decreased insulin receptors

Question 14

Patho of type 2 diabetes
(Lecture, p.706)

Answer 14

-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)

Question 15

Acute complications of DM-
Ketoacidosis
(Lecture, p. 710)

Answer 15

-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

Question 16

Acute complications of dm:
Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)
711

Answer 16

-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

Question 17

Acute complication of DM:
Hypoglycemia
(Lecture, p.710)

Answer 17

-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

Question 18

Chronic hyperglycemia consequences
(Lecture, p. 711, AO)

Answer 18

-Microvascular disease in small blood vessels (retinopathy, nephropathy, neuropathy)
-Macrovascular disease in large blood vessels (cardiovascular disease, stroke, PVD)
-Infection

Question 19

Patho of the chronic complications of DM
(Lecture)

Answer 19

1. Oxidative stress increases reactive oxygen species that cause cell damage
2. 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
3. Protein Kinase C release —> increases insulin resistance, cytokine production, angiogenesis—> causes microvascular complications
4. Glycation—> glucose binds irreversibly to collagen, proteins in RBC, vessel walls and interstitium—> advanced glucation end products with abnormal cell proliferation and inflammatory changes

Question 20

Retinopathy complication of DM
(Lecture, p. 711)

Answer 20

-Microvascular disease

-Happens as a result of damage to blood vessels, vasoconstriction, platelet aggregation, Hypoxemia

1. Non-proliferative: thickening of retinal capillary membrane and increased membrane permeability with vein dilation and micro aneurysm formation
2. Pre-proliferative: retinal ischemia with areas of poor perfusion and infarcts
3. Proliferative: angiogenesis and fibrous tissue formation in the retina or optic disc

-Macular edema, glaucoma, and cataract risk increased

Question 21

Nephropathy complication of DM
(Lecture, p. 712)

Answer 21

-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

Question 22

Neuropathy complications of DM
(Lecture, p.713)

Answer 22

-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

Question 23

Macrovascular complications of DM
(Lecture, p. 713)

Answer 23

1. Cardiovascular disease (HTN, CAD, MI)
2. Stroke (ischemic/ lacunar increased risk)
3. PAD (atherosclerosis of lower extremities with increased risk for
   Ulcers, gangrene, BTK amputation)

Question 24

Autoimmune thyroiditis
What is it
(AO)

Answer 24

-Includes Hashimoto’s

-Group of disorders where body’s immune system attacks thyroid gland

-Can cause both hypo and hyperthyroid

Question 25

Subclinical thyroid disease
(AO)

Answer 25

-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

Question 26

General underlying patho of chronic DM complications
(AO)

Answer 26

-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

Question 27

Hypoaldosteronism
(P.718)

Answer 27

-Caused by adrenal insufficiency (Addison’s disease)