Bio212 vop24 Endoc - Ensemble Video · 11/24/2015 1 Endocrine Pathophysiology •Pituitary gland disorders •Thyroid gland disorders •Adrenal gland disorders •Diabetes and metabolic

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Endocrine Pathophysiology

• Pituitary gland disorders

• Thyroid gland disorders

• Adrenal gland disorders

• Diabetes and metabolic syndrome

Objectives:

Endocrine organ hypo or hyperfunction:

Primary:

• Genetic defect in hormone synthesis or deficiency of component of hormone

• Destruction of gland due to autoimmunity, infection, hemorrhage

• Tumor (benign or malignant)

• Absence of gland

General Endocrine Pathophysiology:

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Endocrine organ hypo or hyperfunction:

Secondary:

• Diseases that lead to endocrine dysfunction

• Paraneoplastic syndromes with tumors

Other Issues:

• Abnormalities in hormone transport, hormone binding and iatrogenic cause of endocrine dysfunction.

General Endocrine Pathophysiology:

Part 1:Pituitary Gland

Disorders

Hypopituitarism: condition in which there are

decreased secretions of pituitary hormones

• Could be a single hormone deficiency or multiple hormone deficiencies (panhypopituitarism) and had multiple endocrine gland effects.

• Etiologies: tumors (adenoma, malignant), lesions (infection, hemorrhage, infarction), genetics or issues with the hypothalamus.

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Hypopituitarism:

Manifestations:• Weakness, fatigue, loss of appetite• Impaired sexual functions (reduced LH: sex hormone

deficiencies, reduced FSH: causes infertility)• Cold intolerance (deficiency of TSH, leads to secondary

hypothyroidism)• postural hypotension, nausea, fever, weakness

(deficiency of ACTH: leads to secondary adrenal insufficiency)

• GH

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Hypopituitarism: Treatment: Hormone replacement therapy- treat baseline hormones1. Cortisol (if ACTH def.)2. T3 (triiodothyronine) and T4 (thyroxine) (if

TSH def.)3. Estrogens and testosterone (if LH and FSH

def.)4. GH (children and sometimes adult)

Hypopituitarism: Growth Hormone (GH) deficiencies

GH Deficiencies in children:

• Etiologies: tumors, congenital problems, deficiencies in GHRH (growth hormone releasing hormone)

• Decreased birth length, reduced growth rate, short statue, increased obesity with immature facial features, delay in skeletal muscle maturation, smaller than normal sexual organs

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Treatment:

• GH replacement therapy (recombinant human growth hormone) as a daily injection for children and possibly continued into adulthood


GH Deficiencies in adults:

• GH can decline with aging

Adult manifestations: increased risk of cardiovascular disease, insulin resistance/metabolic syndrome and inflammation.

Hyperpituitarism: hypersecretion of pituitary

hormonesEtiologies:

• Adenoma (secreting hormones)

• Malignant tumors

Treatment:

• Remove the tumor and replace base hormones accordingly.

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Hyperpituitarism: Manifestations: (according to excess hormones)

• ACTH hypersecretion (presents similar to Cushing Syndrome, hyperpigmentation)

• TSH hypersecretion (presents similar to Grave’s Disease)

• Prolactin hypersecretion (galactorrhea) impotence in males, menstrual irregularities in females

Hyperpituitarism: Growth hormone hypersecretion in

children (before puberty)

• Gigantism

• Characterized by excessive skeletal growth, tall statue, large body.

• Rare, usually treated early

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Hyperpituitarism: Growth hormone (and increased liver

IgF1) hypersecretion in adults

• Acromegaly• Enlargement and increased thickness of bones, soft tissues• Protruding lower jaw, slanting forehead, kyphosis

• Deepened voice, enlarged thyroid cartilage and respiratory tract

• Enlarged heart, hypertension• Increased risk of atherosclerosis, diabetes mellitis

• Headaches, vision difficulties, nerve palsies

Hyperpituitarism: Growth hormone hypersecretion in

adults

Treatment:

• Removal or reduction of tumor

• Dopamine agonists help to reduce GH levels

• GH receptor antagonists

• Somatostatin feedback inhibition of GH

• Treat various clinical manifestations

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Sexual Precocious Puberty: early activation of the

hypothalamus, pituitary and gonadal system.

Etiology:

• Idiopathic or tumors• Causes the early development of sexual characteristics

and fertility

• FSH, LH or releasing hormones from hypothalamus

Females: (before age 7)Males: (before age 9)

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Posterior Pituitary: (not on exam)

• ADH (vasopressin)

• Oxytocin

Part 2:Thyroid Gland

Disorders

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Hypothyroidism: decreased blood levels of thyroxine

(T4) and triiodothyronine (T3).

Etiologies:• Problems with hypothalamus and/or pituitary glands• Surgical removal or radiation therapy• Congenital Hypothyroidism• Dietary iodine deficiency (Endemic Goiter)• Thyroid trauma• Thyroiditis (Hashimoto’s thyroiditis)• Transient states: pregnancy, puberty• Increased risk for underactive thyroid disease with age

TRH TSH T3/T4

Hypothalamus

Anterior Pituitary

Thyroid Gland

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Hypothyroidism:Manifestations:• Decreased metabolic rate• Decreased body temperature (cold

intolerance)• Weakened muscular contraction, delayed

reflexes• Cardiac: bradycardia, reduced CO• GI: slowed motility, constipation• Increased blood cholesterol (increased risk of

atherosclerosis)• Decreased sex drive, irregular menstrual cycle• Weight gain, edema• CNS: slowed thinking, depression, lethargy

Hypothyroidism:Myxedema: significant decline in thyroid hormones characterized by swelling around the eyes, lips, fingers.Myxedematous Coma:

• Life-threatening condition

• Coma, hypothermia, cardiovascular collapse, hypoventilation, and severe metabolic disorders

• More common in elderly women, winter months

• Cannot adequately metabolize sedatives, analgesics, and anesthetic drugs

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no iodine

enzyme defects

T4 TSH

Goiter

Hypothyroidism:Endemic (simple) Goiter: enlargement of the thyroid gland due to a severe iodine deficiency and hypothyroidism.

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Hypothyroidism:Treatment:

• Hormonal replacement therapy levothyroxin(Levothroid, Levoxyl, Synthroid)

Hyperthyroidism: increased blood levels of thyroxine

(T4) and triiodothyronine (T3).

Etiologies:

• Problems with hypothalamus and/or pituitary gland

• Tumors (adenomas, malignant)

• Grave’s Disease (autoimmune disorder)

• Toxic Goiter

TRH TSH T3/T4

Hypothalamus

Anterior Pituitary

Thyroid Gland

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Hyperthyroidism:Manifestations:• Increase in metabolic rate• Increase in heat production (flushed skin, excessive perspiration)• Cardiac: tachycardia• Weight loss• GI: increased motility, diarrhea, malabsorption• CNS: nervous excitability• Increased risk osteoporosis• Muscular tremor• Exophthalmos (protruding eyes from orbits)

Hyperthyroidism:Grave’s Disease: • Autoimmune disorder which causes hyperplasia of the

thyroid gland.

• Auto-antibodies bind to the TSH receptors and stimulate thyroid hormone secretion.

• The antibodies are different enough from normal TSH that they can’t be enzymatically degraded as easily.

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Hyperthyroidism:Toxic Goiter: • Grows from an existing simple or endemic goiter and

develops nodules that begin to secrete too much thyroid hormones.

• Age is a risk factor.

Hyperthyroidism:Thyroid Storm (thyroid crisis): high levels of thyroid hormones that lead to a dangerous, dramatic increase in metabolism.• Precipitated by stress, diabetic ketoacidosis,

manipulation of the thyroid gland during thyroidectomy.

• High body temperature (hyperpyrexia)• CNS: delirium, convulsions• Diarrhea, vomiting, dehydration, hypovolemia,

electrolyte imbalance• Cardiac arrhythmias, cardiogenic shock

Hyperthyroidism:Treatment:

• Drugs to suppress synthesis of T3/T4

• Chemotherapy, radiation

• Surgical removal

• May have to treat for hypothyroidism with hormones after treatments above.

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Part 3: Disorders of the Adrenal Gland

Hypersecretion of adrenal medulla hormones: epinephrine and norepinephrine

• Etiologies: adenoma (pheochromocytoma)

• Hypertension

• Hyperglycemia

• Nervousness, sweating

• Tachycardia

• Exhaustion

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Adrenal Cortical Insufficiency:Etiologies:

• Addison Disease

• Hypothalamus and/or pituitary problem

• Complications associated with withdrawal from corticosteroid medications as with asthma, MS exacerbation

Adrenal Cortical Insufficiency: Addison Disease

• Rare, usually due to autoimmunity, but infections, adrenal gland inflammation/hemorrhage, metastatic cancers, certain drugs.

• Characterized by decreased adrenal cortical hormones and hypersecretion of ACTH

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Manifestations:• Increased loss of sodium, chloride and water and decreased

secretion of potassium (mineral corticoid deficiency/aldosterone) resulting in hyponatremia, hyperkalemia, dehydration, weakness and fatigue, orthostatic hypotension/decreased CO.

• Hyperpigmentation (elevated levels of ACTH) • Poor tolerance to stress (decrease in glucocorticoids) as well

as hypoglycemia, fatigue, weakness, fever, anorexia, nausea, vomiting, weight loss.

• Decrease in androgens (sparse axillary and pubic hair in women)


Addisonian Crisis (acute adrenal crisis):

• Extreme loss of sodium and water could lead to cardiovascular collapse and shock

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Treatment:

• Hormone replacement (for life) and higher dosing required during times of stress: hydrocortisone and Fludrocortisone (a mineralcorticoid if Addison’s)

• Diet and fluid and regular schedule for exercise

Cushing’s Disease (Syndrome): hypersecretion of

glucocorticoids (hypercortisolism)

Etiologies:

• Adenoma or malignant tumor

• Lung cancer (hypersecretion of ACTH)

• Hypothalamus and/or pituitary problem

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Cushing’s Syndrome:Manifestations:• Obesity, fat deposits associated with face (moon face), at

base of neck (buffalo hump) and in abdomen.• Muscle weakness, bone loss, bruising and striae of skin.• Retention of sodium and water, hypertension and

hypokalemia.• Hyperglycemia, increased risk of developing diabetes• Increased androgen secretion (hirsutism: facial hair as well

as mild acne, menstrual irregularities)• Increased risk of osteoporosis• Increases gastric acid secretion (ulceration and bleeding)

Cushing’s Syndrome:Treatment:

• Surgery, irradiation or drugs according to etiology.

• Prophylaxis treatment of pneumocystis jiroveci(carinii).

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Adrenal Virilism: androgen hypersecretion in females resulting in hirsutism, acne, deeper voice, menstrual irregularities.

Part 4: Diabetes and

Metabolic Syndrome

Diabetes mellitis (DM): group of metabolic disorders

characterized by hyperglycemia

Classification:

• Type I (insulin-dependent) diabetes (IDDM)

• Type II (non-insulin dependent) diabetes (NIDDM)

• Gestational Diabetes: develops during pregnancy

• Secondary diabetes due to diseases (Cushing Syndrome, acromegaly, pancreatitis)

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Diabetes mellitis (DM): Type I Diabetes

• Destruction of beta-pancreatic cells either due to an autoimmune reaction or idiopathic reason for the destruction due to a combination of genetic and environmental factors.

• Occurs more commonly in younger people, but can occur later because of the extreme variability in the rate of destruction of beta cells.

• Manifestations are due to absolute lack of insulin, hyperglycemia and breakdown of body fats and proteins. Cells cannot get the glucose they need.


Manifestations:• Polyuria, polydipsia, polyphagia (due to

hyperglycemia and glycosuria)• Weight loss, weakness, fatigue• In untreated diabetes type 1: increased lipid

metabolism causes hyperlipidemia and excessive production of ketones. Bi-products of lipid metabolism can accumulate leading to ketoacidosis and potentially an acidotic coma.

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Diabetic Ketoacidosis (DKA): often precipitated by stress, trauma, infection, hormonal changes, medications• Metabolic acidosis that develops in untreated diabetes type 1

individuals due to accumulation of ketones.• Nausea and vomiting• Elevated blood glucose• Acetone breath odor• Confusion, stupor• Risk of ketoacidotic coma due to the combined effects of

ketoacidosis, dehydration and the toxic effects of ketones on the brain.

• Rapid respirations• Diffuse abdominal pain**Treat DKA with fluid/electrolyte replacement and insulin

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Diabetes mellitis (DM): Type II Diabetes

• Beta cells are able to secrete insulin initially, but the beta cell response may be diminished.

• Insulin resistance: inability of cells (particularly muscle, liver, fat) to take up and metabolize glucose because of a slower cycling of glucose carriers to the cell membrane surface and defective utilization of the glucose that is able to get into cells. This causes an increase in insulin secretion by beta cells and increased production of glucose by the liver.

• Occurs gradually and is often asymptomatic in the beginning

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• Type II much more common than type I• Much stronger genetic component than type I,

probably a combination of environmental factors and genetics

• Less prone to ketoacidosis than type I• Insulin resistance related to metabolic syndrome:

obesity (particular upper body, waist/hip ratio), high levels of plasma triglycerides, low levels of HDLs, hypertension, systemic inflammation, cardiovascular disease, abnormal vascular endothelium, abnormal thrombolysis


Hyperglycemic non-ketotic coma: (rare)

• Stress, infection, etc. in long established type II diabetes, can cause acute demand for insulin overwhelming beta cells, insulin output drops dramatically. Hyperglycemia rises rapidly producing a hyperosmolarity in blood, with heavy diuresis.

• Can lead to cerebral dehydration, coma.

Diabetes mellitis (DM):Chronic complications of diabetes: (both type 1 and II)• Glycated proteins form as plasma proteins (also

hemoglobin) and tissue proteins combine with glucose when there is hyperglycemia. Proteins then function abnormally.

• Microangiopathy: The walls of very small blood vessels become thick and weak and can bleed, leak protein and slow the flow of blood. This disease process of blood vessels can affect the eye, the skin and the kidneys in particular.

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Diabetes mellitis (DM):Chronic complications of diabetes:Microangiopathy:• Diabetic nephropathy: glomerular lesions, kidney hypertrophy

and hyperfiltration, proteinuria• Peripheral neuropathy: development of nerve damage with

sensory loss, abnormal reflexes, numbness, tingling, intense pain, impaired genitourinary function, muscle weakness, decreased vasomotor function.

• GI motility issues: constipation, diarrhea, fecal incontinence, nausea/vomiting, upper abdominal discomfort, delayed stomach emptying

• Retinopathy: microaneurysms, pinpoint hemorrhages, scarring, retinal detachment, cataracts, glaucoma.

• Ischemia of heart muscle.

Diabetes mellitis (DM):Chronic complications of diabetes:Increased risk for hypertension and atherosclerosis:• Glucose deprivation causes the body to have increased

demand for lipid. Hyperlipidemia along with systemic hypertension results in early and severe atheroschlerosis with increased propensity for MI and stroke.

• Skin Ulcerations (particularly of the foot): reduction of blood flow to tissues/lower limbs. Minor wounds don’t heal easily, hypoxia, anaerobic organisms can produce gangrene.

Diabetes mellitis (DM):

Chronic complications of diabetes:

Increased risk for infections:• Soft tissue infections associated with extremities

• Urinary tract infections

• Osteomyelitis

• Dental caries and peridontal disease

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Diabetes mellitis (DM):Screening:• Person without risk factor, 45 yr, 3 yr interval retesting• Consider in younger age if:

• Obese• Family history of diabetes mellitis• High-risk ethnic populations ( black americans, hispanics,

native Americans)• Sedentary lifestyle• Delivering a >9lb baby or have had gestational diabetes• Polycystic ovarian syndrome• Have HTN or hyperlipidemia• Previous testing with impaired glucose tolerance or impaired

fasting glucose (IFG)

Diagnosis:• Glycolated hemoglobin test

• Blood tests (blood glucose tests)

• Urine tests

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Stage Fasting plasma glucose (FPG)

Casual (random) plasma glucose:blood drawn at any time

Oral Glucose Tolerance Test (OGTT)

Diabetes FPG > 126 mg/dL Casual >200 mg/dL+ symptoms

2 hr plasma glucose >200 mg/dL

Impaired glucose tolerance

FPG > 110 and < 126 mg/dL

2 hr plasma glucose > 140 and <200 mg/dL

Normal FPG < 110 mg/dL 2 hr plasma glucose < 140 mg/dLb

Treatment: normalization of blood glucose to prevent short and long term complications

Diabetes Type I

• Insulin (divided doses oral & injectable, insulin pump), regular, intermediate and long-acting

• Diet and exercise

Diabetes Type II

• Diet and Exercise (as weight is reduced, the insulin receptor numbers increase, decreasing insulin resistance).

• Drugs: Sulfonylureas (increase release of insulin from beta cells), biguanide(inhibit hepatic breakdown and release of glucose), alpha-glucosidase inhibitors (inhibit enzymes that break down carbohydrates in intestines), thiazolinediones (decrease insulin resistance)

• Insulin

Diabetes mellitis (DM):Problems with maintaining blood sugar with insulin therapy:

• Hypoglycemic coma: results from brain glucose deprivation. This can be caused by an accidental excessive insulin dose or not eating enough along with insulin doses.

• Somogyi effect: rebounding high blood sugar that is in response to low blood sugar. Insulin-induced posthypoglycemic episodes. Increase in catecholamines, glucagon, cortisol and GH increase blood sugar.

• Dawn phenomenon: abnormal rise in morning blood sugar due to a surge of bodily hormones (especially GH) secreted between 4:00 and 5:00 am while insulin is waning.

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Bio212 vop24 Endoc - Ensemble Video · 11/24/2015 1 Endocrine Pathophysiology •Pituitary gland disorders •Thyroid gland disorders •Adrenal gland disorders •Diabetes and metabolic

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