Endocrine System

Question 1

1. What are the 6 ways by which the target tissue can receive the wrong amount of hormone?

Answer 1

Actual over/under production of hormone
The feedback system isn’t working correctly, so release of hormone isn’t correct
Inadequate blood supply to target tissues, so delivery is inadequate
Inadequate levels of serum carrier protein, if required
The hormone is being inactivated too quickly/slowly
Abnormal production of hormone by uncontrolled ectopic sources

Question 2

1. In what 3 ways can the receptor function be abnormal?

Answer 2

Hormone arrives at the target tissue, but finds abnormal cell receptor function (primarily in water soluble hormones, e.g., insulin), for e.g.:
Decrease in number of receptors
Impaired receptor function – doesn’t recognize hormone
Presence of antibodies that act as competitive inhibitors or mimic hormone action

Question 3

1. What does “altered intracellular response” mean, in reference to causing endocrine disorders?

Answer 3

The series of reactions inside the cell that allow the hormone to have an effect on the metabolic pathways do not work correctly.

Question 4

1. What 2 events can cause diabetes insipidus?

2. What are clinical manifestations of diabetes insipidus?

Answer 4

Caused by either insufficient production/transport/release of ADH, or inadequate response of the renal tubules to ADH.
Clinical manifestations: thirst, polyuria

Question 5

1. What does SIADH stand for and what is it?
2. What is the most common cause of SIADH?
3. What type of hyponatremia is caused by SIADH?
4. What are 3 clinical manifestations of SIADH?

Answer 5

High levels of ADH
most common cause (but not the only cause) is ectopic production of ADH by tumours in other organs (duodenum, stomach, bladder, etc.)
Medications are a common cause in the elderly (hypoglycemic, narcotics, chemotherapeutic agents, NSAIDs, etc.)
Clinical manifestations result from hyponatremia (what kind?): anorexia, fatigue that can progress to confusion, lethargy, convulsions with extreme drops in sodium levels.

Question 6

1. What are two causes for hypopituitarism, and which of these is most common?
2. What are 2 causes of damage to the pituitary gland?
3. What is panhypopituitarism?

Answer 6

Results from either an inadequate supply of hypothalamic-releasing homones (damage to pituitary stalk) or inability of the pituitary gland to produce hormones.
Most common cause is problem within the pituitary gland: infarction, tumour, aneurysm.
Also brought on through head trauma, infections, etc.
Damage can result in deficiency in some or all pituitary hormones (panhypopituitarism), depending upon which area of the pituitary is affected.

Question 7

1. What is hyperpituitarism caused by?

1. How might an adenoma affect the secretion of various hormones by the pituitary?

Answer 7

Usually caused by tumour (adenoma)
May get oversecretion of hormone by tumour (hormone will be the one normally produced by the tissue which gave rise to the tumour), accompanied by undersecretion of hormones from tissues surrounding tumour.
Tumour may cause disturbance in vision (optic chiasm is adjacent).

Question 8

1. Describe the difference between primary, secondary and tertiary disorders of the glands involved in the hypothalamus-pituitary-target gland axis of control.

Answer 8

Primary: if there is a problem with the target gland responsible for producing the hormone
Secondary: if there is a problem with the pituitary gland releasing/inhibiting hormone release.
Tertiary: if there is a problem with the hypothalamus production of the controlling hormone for the pituitary.

Question 9

1. Name two glands and one secretion of each that could be affected by the hypothalamus-pituitary-target gland axis of control.

Answer 9

Thyroid (thyroxin)
Adrenal cortex (cortisol)

Question 10

1. What are 4 symptoms/signs of thyrotoxicosis and what does this syndrome result from?
2. Name an example of a primary disorder, and of a secondary disorder that would result in thyrotoxicosis.
3. Name and explain the mechanism of the cause of Graves disease.

Answer 10

Hyperthyroidism
Thyrotoxicosis results from increased levels of thyroid hormones (T3 and T4)
Exophthalmic goiter, weight loss, heat sensitivity, increased metabolic rate
Primary (e.g., Graves disease) or secondary (e.g., TSH secreting pituitary adenoma)
Graves disease from Type 2 hypersensitivity RXN (antibodies have been produced against the TSH receptors on thyroid gland cells, resulting in stimulation of thyroid hormone production.)

Question 11

1. Name 3 causes for a primary hypothyroid disorder. Which one of these is an autoimmune disease?
2. Describe 1 cause for a secondary hypothyroid disorder.
3. Name 4 signs/symptoms for hypothyroidism.

Answer 11

Most common disorder of thyroid function
Primary (accounts for 99%) can result from autoimmune RXN (=Hashimoto disease: autoantibodies + autoreactive T lymphocytes, induced apoptosis, etc., which destroys thyroid gland), drugs, radiation therapy, etc.
Secondary may result from pituitary tumour compressing surrounding pituitary cells (or treatment of pituitary tumour)= decreased TSH.
Low metabolic rate, cold intolerance, lethargy, myxedema

Question 12

25. What is diabetes mellitus characterized by?

Answer 12

Characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

Question 13

27. What is the mechanism behind the development of Type 1 diabetes?

Answer 13

Most common pediatric chronic disease
Slowly progressive autoimmune T cell-mediated disease that destroys beta cells of the pancreas.
Destruction is related to interaction between genetics and the environment
Cause antigens (autoantigens) to develop on the surface of pancreatic beta cells and then circulate in the bloodstream/lymphatics.
Immune system responds (both cellular and humoral), resulting in beta cell destruction
Hyperglycemia develops

Question 14

28. How does glucagon secretion play a role in Type 1 diabetes?
29. Describe 5 clinical manifestations of Type 1 diabetes.

Answer 14

Adding to the problem is that insulin suppresses the secretion of glucagon (a hormone that stimulates glycogenolysis and gluconeogenesis). A decrease in the production/secretion of insulin allows glucagon secretion to increase, leading to glycogenolysis and gluconeogenesis = increased hyperglycemia.
Glucose accumulates in the blood
Appears in the urine
Polyuria and thirst
Wide fluctuations in blood glucose occur
Protein and fat breakdown occur, resulting in weight loss
High levels of circulating ketones (diabetic ketoacidosis (DKA)).

Question 15

30. What are 3 risk factors for Type 2 diabetes?

31. What are 4 disorders grouped under “metabolic syndrome” and what is the significance of metabolic syndrome?

Answer 15

Non-insulin dependent diabetes mellitus
Genetic-environmental interaction appears to be responsible
Risk factors: age, obesity, hypertension, physical inactivity and family history.
Metabolic syndrome: a collection of disorders that confer a high risk of developing type 2 diabetes: central obesity, dyslipidemia, prehypertension, elevated fasting blood glucose level.

Question 16

32. What is insulin resistance?

33. What are 3 ways that adipose tissue contributes to the development of insulin resistance?

Answer 16

Defined as: Below optimal response of insulin-sensitive tissues (liver, muscle and adipose tissue) to insulin
is associated with obesity, which contributes to the development of insulin resistance in the following manners:
Adipose tissue produces hormones (adipokines) that are associated with decreased insulin sensitivity
Intracellular deposits of cholesterol and TG are found in obese individuals and interfere with intracellular insulin signaling, thus decreasing tissue responses to insulin.
Adipose tissue releases inflammatory chemicals (e.g., TNF-alpha), which are toxic to beta cells and induce insulin resistance

Question 17

34. Describe the development of Type 2 diabetes.

Answer 17

Due to insulin resistance, the beta cells produce more and more insulin (compensatory hyperinsulinemia).
Compensatory hyperinsulinemia prevents the clinical appearance of diabetes for many years.
However eventually beta-cell dysfunction develops and leads to both a decrease in the number of beta-cells and a reduction of normal beta-cell function.
The remaining functioning beta cells undergo “exhaustion” from increased demand for insulin biosynthesis.
As with Type 1 diabetes, there is a increase in glucagon secretion, which leads to further hyperglycemia.

Question 18

35. What are 3 non-specific symptoms that an individual with Type 2 diabetes may have?

Answer 18

Not as specific as Type 1 diabetes
Many more children and adolescents are developing Type 2, but still generally affects those >30 yrs.
Individual often overweight, dyslipidemic, hyperinsulinemic and hypertensive.
May have classic symptoms: polyuria, polydipsia, but more often have nonspecific symptoms such as fatigue, pruritus, recurrent infections, visual changes, etc.

Question 19

38. List 5 acute complications of diabetes mellitus.
39. Describe the “insulin shock/reaction”.
40. What two metabolic processes have to occur in order for ketoacidosis to develop?
41. List 4 clinical manifestations of ketoacidosis.
42. Describe the Somogyi effect.
43. Describe the dawn phenomenon.
44. What does HHNKS stand for?
45. Describe the development of HHNKS, along with 3 clinical manifestations.

Answer 19

Hypoglycemia
“insulin shock/reaction”
Pallor, tremor, tachycardia, palpitations, dizziness, confusion, seizures, coma.
More so in Type 1 than Type 2, as individuals with Type 2 DM still have mechanisms to increase blood glucose levels. (But can occur with those on insulin replacement therapy).
Requires immediate replacement of glucose
Diabetic ketoacidosis (DKA)
With insulin deficiency (more with Type 1), lipolysis is enhanced = more FA delivered to the liver. Gluconeogenesis is also occurring, leading to the production of more ketones than can be used in the body. Builds up = metabolic acidosis
Hyperventilation, dizziness, nausea, CNS depression.
Somogyi effect
Hypoglycemia-hyperglycemia alternating episodes
Insulin induced hypoglycemia occurs, which causes the release of epinephrine, growth hormone, corticosteriods (cortisol).
These hormones stimulate gluconeogenesis, leading to hyperglycemia (treat it with insulin!)
“rebound hyperglycemia”
Dawn phenomenon
Early morning rise in blood glucose levels with no hypoglycemia during the night.
Related to increased release of growth hormone during the night (decreases metabolism of glucose by muscle and fat)
HHNKS (hyperosmolar hyperglycemic nonketotic syndrome)
Complication of Type 2 – can be fatal
High glucose levels + high plasma osmolarity + dehydration, but no ketoacidosis. (There’s enough insulin to inhibit lipolysis, but not enough to decrease glucose levels in blood)
If blood glucose is high, the kidneys excrete more fluid. If this fluid is not replaced (result of illness, for e.g.,) dehydration occurs.
Excessive dehydration pulls water out of the cells, including brain cells.
Weakness, dehydration, polyuria, neurological signs/symptoms (aphasia, for e.g.,)
More common in elderly people. Onset can be very gradual – may be mistaken for a stroke.

Question 20

46. List the 4 general categories of chronic complications of diabetes mellitus.
47. Describe 2 metabolic chronic complications of diabetes mellitus.

Answer 20

Metabolic: (466)
Tissues that do not require insulin to import glucose (kidneys, RBCs, blood vessels, eye lens, nerves) cannot down-regulate the uptake. Excess glucose is converted into sorbitol. The build up of this compound can result in problems in the nerves (Schwann cell damage, disruption of conduction), eye lens (swelling due to osmotic pressure)
Long term excess glucose can result in glucose permanently binding to proteins inside/outside cells and interfering with cell metabolism.
. Macrovascular: Lesions in large and medium sized arteries (468)
Due to attachment of glycosylated compounds (compounds containing glucose) to proteins in the vessel wall.
Increased risk for:
accelerated atherosclerotic disease
Coronary artery disease (most common cause of morbidity and mortality in people with DM).
Stroke – twice as common in those with DM.
Peripheral vascular disease – gangrene, ulcers, etc. Often involves arteries below the knee. Occlusions of the small arteries cause most of the gangrenous changes of lower extremities.
Microvascular: diseases of the capillaries (467)
Thickening of capillary basement membrane, endothelial hyperplasia, thrombosis.

Diabetic retinopathy
Leading cause of blindness
Results from increased capillary permeability, ischemia, etc.
Diabetic nephropathy
Most common cause of end stage kidney disease
Hyperglycemia contributes to kidney disease. The glomeruli are injured by protein denaturation and high renal blood flow from hyperglycemia.
Diabetic neuropathy
Due to metabolic factors (including build up of sorbitol in neurons) and vascular factors (ischemia).
Sensory deficits are more common than motor and often involve the extremities (sock and glove pattern).

Infection: (468)
Those with DM are at increased risk of infection due to impaired senses (more likely to have an accident), impairment of the immune system, increase in pathogen growth due to higher level of glucose in body fluids.