endocrine disorders quiz

Question 1

Name, and describe the causes of, primary adrenal cortical insufficiency.

Answer 1

Addison disease – usually autoimmune destruction of adrenal cortex, so lose all adrenal cortex hormones (cortisol & aldosterone), more rarely from tumors, infective agents & ACTH levels are elevated because of lack of feedback inhibition from cortisol

Question 2

Describe the causes of secondary adrenal cortical insufficiency. (Are both cortisol and aldosterone affected?)

Answer 2

Mainly due to withdrawal of glucocorticoids that have been used therapeutically

Can occur as a result of hypopituitarism or because pituitary gland has been surgically removed, or due to a hypothalamic defect (cortisol is affected)

Question 3

Describe the typical manifestations of adrenal cortical insufficiency (easier to learn if you relate them to low levels of cortisol and aldosterone) and treatment.

Answer 3

Hyperpigmentation, weight loss, hypoglycemia, fatigue, poor tolerance to stress, urinary losses of sodium and water, retention of potassium, hypotension

Treatment for chronic primary condition = ongoing replacement of glucocorticoids and mineralocorticoids. Have limited ability to respond to stress

Question 4

Describe an acute adrenal crisis and its treatment.

Answer 4

Life-threatening response to stress or minor illness -> nausea, weakness, hypotension, hypovolemic shock -> death

Treatment for crisis condition = replacement of glucocorticoids, mineralocorticoids, glucose and salts

Question 5

Describe the three main forms of glucocorticoid hormone excess.

Answer 5

Pituitary form = results from excessive production of ACTH by a tumor of the pituitary gland = “Cushing’s disease”

Adrenal form = caused by a benign or malignant adrenal tumor

Ectopic form = non-pituitary ATCH-secreting tumor (I.e. a paraneoplastic syndrome)

Question 6

Describe the clinical manifestations of glucocorticoid excess.

Answer 6

Hyperglycemia; development of insulin resistance leads to Type 2 diabetes mellitus

Altered fat metabolism produces round face, “buffalo hump”, protruding abdomen

Protein breakdown produces thin arms and legs

Destruction of bone proteins and reduced calcium absorption in the intestine may produce osteoporosis

Since glucocorticoids have weak mineralocorticoid activity, increased amounts will cause increased reabsorption of sodium and water, and secretion of potassium

Inflammatory and immune responses are inhibited

Question 7

Differentiate between Cushing disease and Cushing syndrome.

Answer 7

syndrome = too much cortisol – could be paraneoplastic syndrome, adrenal gland tumour (many different causes)

disease = too much cortisol – tumour specifically in pituitary gland (one specific cause)

Question 8

1. What 3 general causes lie behind endocrine disorders?

Answer 8

The target tissue receives too much or too little hormone

Hormone arrives at the target tissue, but finds abnormal cell receptor function (primarily in water soluble hormones)

Altered intracellular response to the hormone-receptor complex

Question 9

2. Be familiar with the ways by which the target tissue can receive the wrong amount of hormone.

Answer 9

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 10

3. Be familiar with the ways in which the receptor function can be abnormal.

Answer 10

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 11

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

Answer 11

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

Question 12

5. Be able to explain the hypothalamic-pituitary-target gland axis.

Answer 12

part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress

A major component of the homeostatic response is the hypothalamic-pituitary-adrenal (HPA) axis, an intricate, yet robust, neuroendocrine mechanism that mediates the effects of stressors by regulating numerous physiological processes, such as metabolism, immune responses, and the autonomic nervous system (ANS).

Question 13

6. Explain primary, secondary and tertiary disorders involving the hypothalamus-pituitary-target gland axis of control and give two examples of endocrine glands that can be affected by secondary or tertiary disorders.

Answer 13

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.

Thyroid (thyroxin) – Adrenal cortex (cortisol)

Question 14

7. What are the two general causes of hypothalamic-pituitary system dysfunction? Which is the most common cause of apparent hypothalamic dysfunction? Be familiar with examples of causes.

Answer 14

1. interruption of portal blood flow or damage to the pituitary stalk (most common)

– causes include brain tumours lesions, rupture after head injury, surgical transection, aneurysms (dilated blood vessels)

2. hypothalamic disorders causing a lack of releasing hormones from the hypothalamus -> absence of pituitary hormones

causes include tumours, stroke, head trauma or surgery, malnutrition, radiation and genetic disorders

Question 15

8. Describe two possible causes for diabetes insipidus.

Answer 15

Caused by either insufficient production/transport/release of ADH, or inadequate response of the renal tubules to ADH

Question 16

9. What are two clinical manifestations of diabetes insipidus?

Answer 16

Clinical manifestations: thirst, polyuria

Question 17

10. What does SIADH stand for and what hormone is involved? Are levels of this hormone too high or low?

Answer 17

Syndrome of inappropriate antidiuretic hormone secretion

High levels of ADH

Question 18

11. What is the most common cause of SIADH?

Answer 18

most common cause (but not the only cause) is ectopic production of ADH by tumours in other organs (duodenum, stomach, bladder, etc.)

Question 19

12. What type of hyponatremia is caused by SIADH? Which system is noticeably affected by extreme drops in sodium levels?

Answer 19

Euvolemic hyponatremia

Blood

Question 20

13. What are two causes for hypopituitarism, and which of these is most common?

Answer 20

Results from either an inadequate supply of hypothalamic-releasing hormones (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.

Question 21

14. What is panhypopituitarism?

Answer 21

condition in which the production and secretion of all hormones by the pituitary gland is reduced

Question 22

15. Be familiar with possible manifestations of hypopituitarism (hopefully memory of 1203 section of the endocrine system can help out here).

Answer 22

(ACTH = decreased cortisol release (hypoglycemia, etc.),

TSH = decreased thyroxine release (decreased metabolic rate, etc.),

FSH/LH = decreased estrogen, progesterone, testosterone release (issues with reproductive system),

GH = decreased growth in children, decreased muscle mass, etc. in adults

Question 23

16. What is hyperpituitarism usually caused by?

Answer 23

Usually caused by benign slow-growing tumour (adenoma)

Question 24

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

Answer 24

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.

Question 25

18. Which two anterior pituitary hormones are usually affected? (Notice that neither of these is one that affects another endocrine gland).

Answer 25

GH and prolactin are affected

greater secretion of these hormones, with increased GH causing gigantism in children and acromegaly in adults, and increased prolactin causing galactorrhea and menstrual disturbances in women / visual impairments in men

Question 26

19. What problem can arise that is a result of the physical presence of the tumour?

Answer 26

As the tumour grows, its physical mass may press on the adjacent optic chiasm and cause a disturbance in vision

Question 27

20. What are 4 symptoms/signs of thyrotoxicosis and from what does this syndrome result?

Answer 27

– Exophthalmos (Graves disease manifestation), weight loss, heat sensitivity, increased metabolic rate

Question 28

21. Name an example of a primary disorder, and of a secondary disorder that would result in thyrotoxicosis.

Answer 28

– Primary (e.g., Graves disease*) or secondary (e.g., TSH secreting pituitary adenoma)

Question 29

22. Name and explain the mechanism of the cause of Graves disease.

Answer 29

Graves disease results 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 30

23. Name and describe the most common cause for primary hypothyroidism. Be familiar with two other causes for a primary hypothyroid disorder.

Answer 30

Primary (accounts for 99%) most commonly results from autoimmune RXN

Hashimoto disease: autoantibodies, autoreactive T lymphocytes, induced apoptosis, etc. destroy thyroid gland), but can also result from drugs, radiation therapy

Question 31

24. Describe 1 cause for a secondary hypothyroid disorder.

Answer 31

Secondary may result from pituitary tumour compressing surrounding pituitary cells (or treatment of pituitary tumour), causing a drop in levels of TSH

Question 32

33. Define prediabetes and outline how insulin imbalances may arise that produce this condition.

Answer 32

impaired fasting plasma glucose and impaired glucose tolerance

An absolute insulin deficiency, Impaired release of insulin by the pancreatic beta cells, Inadequate or defective insulin receptors, Production of inactive insulin or insulin that is destroyed before it can carry out its action

Question 33

34. Define the three key clinical manifestations of diabetes mellitus – the “three Ps”.

Answer 33

Polyuria – Excessive urination

Polydipsia – Excessive thirst, from dehydration

Polyphagia – Excessive hunger: cells in a starvation state, so person feels hungry despite eating huge amounts of food

Question 34

35. Define type 1 diabetes and describe the pathogenesis of the disease.

Answer 34

Beta cell destruction leading to absolute insulin deficiency.

Slowly progressive autoimmune T cell-mediated disease that destroys beta cells of the pancreas&raquo_space;» A possible triggering event that involves an environmental agent (e.g. a virus) that incites an immune response&raquo_space;» Autoantigens develop on the surface of pancreatic beta cells and then circulate in blood and lymph&raquo_space;» Autoantigens stimulate cellular and humoral immune responses that result in beta cell destruction → hypoinsulinemia&raquo_space;» Hyperglycemia develops

Question 35

36. Describe the clinical manifestations of type 1 diabetes, including laboratory tests used to confirm the diagnosis (you don’t have to memorize the levels of glucose that are part of each test).

Answer 35

Glucose accumulates in the blood = Hyperglycemia, Glucose appears in the urine as it exceeds “renal threshold” for glucose = glycosuria, The three P’s – cardinal features of diabetes mellitus, Wide fluctuations in blood glucose occur, Protein and fat breakdown = weight loss, Diabetic ketoacidosis (DKA) due to starvation state

Random glucose test, fasting glucose test, 2 hour post load glucose

Question 36

37. Define type 2 diabetes and be familiar with its risk factors.

Answer 36

A condition characterized by hyperglycemia resulting from the impaired utilization of insulin

older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity

Question 37

Define insulin resistance, and explain the mechanisms related to obesity that underlie its development.

Answer 37

a disorder in which the cells do not use insulin properly — Below optimal response of insulin-sensitive tissues (liver, muscle and adipose tissue) to insulin

1. Adipose tissue produces hormones (adipokines) that are associated with decreased insulin sensitivity
2. Intracellular deposits of cholesterol and triglycerides found in obese individuals interfere with intracellular insulin signalling
3. Adipose tissue releases inflammatory cytokines (e.g. TNFalpha) which are toxic to beta cells and induce insulin resistance

Question 38

39. Describe the development of Type 2 diabetes.

Answer 38

1. Insulin resistance occurs.
2. Compensatory hyperinsulinemia results and prevents significant hyperglycemia and its effects (the clinical appearance of diabetes – the three P’s), possibly for many years. However, there may still be lower levels of hyperglycemia, as the beta cells of the pancreas cannot make enough insulin to completely control glucose levels.
3. 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 cells undergo “exhaustion” from increased demand for insulin biosynthesis.
4. The decrease in insulin production leads to significant hyperglycemia: due to intake of glucose with meals, and due to increased glucose production by the liver (usually depressed by insulin)

Question 39

Describe the clinical manifestations of type 2 diabetes, including diagnostic laboratory tests (you don’t have to memorize the levels of glucose that are part of each test).

Answer 39

Individual is often overweight, but may have recent unexplained weight loss

Hyperglycemia and glycosuria

Often has diagnostic features of metabolic syndrome

May have classic symptoms: polyuria, polydipsia, but more often have nonspecific symptoms such as fatigue, pruritus (itching), recurrent infections, visual changes, etc.

Fasting blood glucose test > 7mmol/L (on 2 occasions)

Random plasma glucose or oral glucose tolerance test > 11.1 mmol/L

Question 40

41. Define metabolic syndrome.

Answer 40

a collection of disorders that confer a high risk of developing type 2 diabetes: central obesity, dyslipidemia (high TG, low HDL), prehypertension, elevated fasting blood glucose level

Question 41

42. What is gestational diabetes mellitus?

Answer 41

Any degree of glucose intolerance with onset or first recognition during pregnancy

Question 42

43. a. Hypoglycemia

Answer 42

– “insulin shock/reaction”, due to mismatching insulin need with supply

– 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

Question 43

b. Diabetic ketoacidosis

Answer 43

– With insulin deficiency (more with Type 1), lipolysis is enhanced = more FA delivered to the liver. Gluconeogenesis is also occurring (due to increased levels of glucagon responding to decreased levels of insulin), leading to the production of more ketones than can be used in the body. Builds up = metabolic acidosis

– Hyperventilation, dizziness, nausea, CNS depression.

Question 44

c. Somogyi effect

Answer 44

– Hypoglycemia-hyperglycemia alternating episodes

– Insulin induced hypoglycemia occurs (missed late night snack?), which causes the release of epinephrine, growth hormone, corticosteroids (cortisol).

– These hormones stimulate gluconeogenesis, leading to hyperglycemia =“rebound hyperglycemia”

– Worse effect if combined with dawn phenomenon.

Question 45

d. Dawn phenomenon

Answer 45

– Early morning rise in blood glucose levels (occurs in everyone).

– Related to increased release of growth hormone, epinephrine, cortisol in early morning, causing increased blood sugar to prepare body for activity.

– People who produce insulin

– no problem, the increased glucose is taken into the cells, as it should be. People with no insulin continue with high blood sugar

Question 46

e. Hyperosmolar hypoglycemic syndrome

Answer 46

Complication of Type 2 – can be fatal (also called HHNKS = Non-Ketotic, as ketosis doesn’t develop)

Very high glucose levels ( 34 mmol/L (normal = 4-7 mml/L) + high plasma osmolality (> 320 mOsm/L (normal = 275-295 nOsm/L)+ dehydration (no ketoacidosis)

If blood glucose is high (could be due to a recent illness or surgery which can cause the release of hormones like cortisol, or undiagnosed or unmonitored Type 2), the kidneys excrete more fluid. If this fluid is not replaced, dehydration occurs. (This further concentrates the blood glucose.)

Excessive dehydration pulls water out of the cells, including brain cells.

Weakness, dehydration, polyuria, neurological signs/symptoms (confusion, aphasia, for e.g.,)

More common in elderly people (decreased thirst mechanism). Onset can be very gradual – may be mistaken for a stroke

Question 47

44. Name and describe three metabolic changes that can occur with chronic hyperglycemia. Advanced Glycation End Products (AGEs):

Answer 47

Advanced Glycation End Products (AGEs): Long term excess glucose can result in glucose permanently binding to proteins inside/outside cells (called glycation) and interfering with cell metabolism, producing endothelial changes / microvascular damage

Question 48

a. Diabetic retinopathy

Answer 48

– a leading cause of blindness in DM

– results from increased capillary permeability and ischemia of the retinal blood supply

– leaking macular capillaries can lead to macular edema producing severe loss of central vision

Question 49

b. Diabetic nephropathy

Answer 49

The glomeruli are progressively injured by glycation and high blood pressure.

– Most common cause of end stage renal disease (complete loss of kidney function)

– Due to metabolic factors (including build up of sorbitol in neurons) and vascular effects (ischemia)

– Sensory deficits are more common than motor and often involve the extremities. Loss of sensation in toes / fingers (“sock and glove syndrome”) means minor injuries go unnoticed, may become infected, gangrenous

Question 50

d. Infection

Answer 50

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

Question 51

44. Name and describe three metabolic changes that can occur with chronic hyperglycemia. Inappropriate protein kinase C activation

Answer 51

PKC is an intracellular messenger controlling various cell functions including permeability and vasodilation in blood vessels. Activation of PKC by the presence of high levels of glucose is linked to vascular damage in the retina, nerves and kidneys

Question 52

44. Name and describe three metabolic changes that can occur with chronic hyperglycemia. Polyol pathway:

Answer 52

Tissues that do not require insulin to import glucose (kidneys, RBCs, blood vessels, eye lens, nerves) cannot decrease the uptake. Excess glucose is converted into sorbitol which is osmotically active. The build up of sorbitol may damage Schwann cells producing neuropathies, or damage the eye lens from swelling due to osmotic pressure

Question 53

46. To what are macrovascular disorders due?

Answer 53

Due to lesions in large and medium sized arteries, caused by AGEs and poor tissue oxygenation

Question 54

47. Name and be able to describe 4 macrovascular disorders that can be caused by long-term diabetes mellitus.

Answer 54

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 – Narrowing or obstruction of peripheral arteries, usually below the knee, as a result of atherosclerosis and inflammation, can lead to neuropathy, diabetic foot ulcers and dry and sometimes wet gangrene