Lab Investigation of Endocrine Disorders Flashcards
1
Q
Hypothalamic Pituitary Axis
A
- TRH is secreted from the hypothalamus will bind to the anterior pituitary gland and cause the secretion of TSH
- TSH is responsible for the production of thyroid hormones (T3 and T4) from the thyroid gland
- These then act on multiple peripheral tissues.
- Circulating T3 and T4 under the control of negative feedback control the hypothalamic-pituitary levels
- T4 is the main hormone secreted by the thyroid gland, however T3 is more biologically active,
2
Q
How is T3 formed?
A
By the peripheral conversion from T4
3
Q
The function of thyroid hormones
A
- Essential for normal growth and development
- Increase BMR and affect many metabolic processes
- Synthesized in thyroid via a series of enzyme-catalyzed reactions
- These reactions begin with the uptake of iodide into the gland
- Synthesis and release is controlled by TSH
- T4 is the main hormone secreted by the thyroid but T3 is more active and is made by the conversion of T4 to T3
- Effects are mediated via activation of the nuclear receptor because
4
Q
Euthyroid
A
Normal range thyroid function
5
Q
Hypothyroid
A
Below average function
6
Q
Hyperthyroid
A
Above average function
7
Q
Primary hyper/hypothyroidism
A
Dysfunction is in the thyroid gland
8
Q
Secondary hyper/hypothyroidism
A
Problem with the pituitary
9
Q
Tertiary hyper/hypothyroidism
A
A problem in the hypothalamus
10
Q
Hyperthyroidism
A
- Excessive production of thyroid hormones = thyrotoxicosis
- Clinical features: weight loss, heat tolerance, palpitations, goitre, eye damage. In extreme cases, thyroid storm also occurs.
11
Q
Causes of hyperthyroidism
A
- Graves’ disease - most common
- Toxic multinodular goitre
- Toxic adenoma
- Secondary causes can include excess TSH production which is rare
12
Q
Thyrotoxicosis
A
Excessive production of thyroid hormones
13
Q
Hypothyroidism
A
- Deficient production of thyroid hormones
- Clinical features: weight gain, cold intolerance, lack of energy, goitre. Congenital development abnormalities
- Investigations: raised TSH, and reduced T4. Reduction in TSH and T4 suggests a secondary hypothyroidism which means it is to do with hypo-functionality of the pituitary gland
14
Q
Causes of hypothyroidism
A
- Auto-immune thyroiditis = Hashimoto’s
- Via thyroid peroxidase antibodies
- Iodine deficiency
- Toxic adenoma
- If it is secondary, it can be lack of TSH.
15
Q
Division of the adrenal gland
A
- Zona Glomerulosa
- Zona Fasciculata
- Zona Reticularis
16
Q
Function of the Zonas of the adrenal cortex
A
All three are responsible for synthesising different types of hormones.
ZG = responsible for minerocorticoids
ZF = responsible for glucocorticoids
ZR = responsible for adrenal androgens
17
Q
What substrate do the hormones start off with?
A
Start with the same substrate which is cholesterol, and they then follow different pathways with different enzymes that help them differentiate.
18
Q
How does functional zonation of the cortex occur?
A
- Blood flows from the cortex to the inner medulla.
- Layer specific enzymes are responsible for steroid synthesis in one layer and can inhibit different enzymes in subsequent layers.
- Results in functional zonation of cortex with different hormones made in each layer
19
Q
Which gene is absent in congenital hyperplasia?
A
CYP21A
20
Q
What is the function of CYP21A?
A
A gene fro 21-hydroxylase which is the enzyme responsible for converting progesterone into aldosterone.
21
Q
Aldosterone
A
- A mineralocorticoid
- The function is to balance the water and salt levels in the body in order to maintain plasma volume which is linked to maintenance of blood pressure over a long time
- It maintains extracellular water levels by reabsorbing Na+ from the kidneys and therefore water follows as well due to osmosis.
- It is signalled via a drop in blood pressure and therefore blood volume and the RAAS system.
22
Q
Cortisol
A
- Glucocorticoids
- Function to control metabolism and immune function
- Stress increases release but minimal levels are essential for normal function
23
Q
Action of cortisol on the CVS
A
- Very important for blood pressure
- No cortisol means low blood pressure
- This is because it counteracts the effects of NO
- Therefore, prevents too much vasodilation from occurring
24
Q
Action of cortisol on glucose metabolism
A
- Acts to spare glucose which means it allows to maintain high glucose levels
- It will promote insulin resistance in skeletal muscle
- This is an adaptive response in order to preserve glucose and use other energy sources such as fat.
- Promotes gluconeogenesis by the liver and promotes the oxidation of fatty acids
- These effects will lead to an increase in blood glucose levels and therefore promoting insulin secretion which will promote lipogenesis
- Therefore, the 2 ways to counteract each other, this is why excess cortisol can lead to fat deposition in certain areas of the body.
25
How is cortisol secretion controlled?
- Synthesis and release regulated by HPA axis
| - CRH and ACTH
26
How is aldosterone secretion controlled?
Controlled by RAAS
27
How are adrenal androgens controlled?
ACTH and not gonadotrophins
28
Cortisol and circadian rhythm
- Cortisol secretion in a circadian rhythm which means a random plasma cortisol reading would not work.
- It would not exclude abnormalities unless way outside the normal range.
- The levels typically rise in the morning
- Therefore, to study levels of cortisol a 24-hour urine sample is needed.
29
ACTH receptor
Present on the adrenal glands: a Gs protein-coupled receptor, so via cAMP stimulates cholesterol uptake and steroid synthesis.
30
Conn's disease
- Aldosterone excess
- This leads to hypertension and NOT hypernatremia because it reabsorbs both sodium and water.
- Secondary hyperaldosteronism can be caused by anything that stimulates the RAAS system
- Kidney enzymes convert cortisol to cortisone, which prevents the activation of the mineralocorticoid receptors by cortisol.
- Therefore, anything that inhibits this enzyme could produce hyperaldosteronism
31
Cushing's syndrome
- Cortisol excess
- This is caused by anything that leads to excess cortisol.
- Whereas Cushing's disease is caused by an adenoma in the pituitary gland.
- ACTH secreting tumours are secondary, and negative feedback is still present.
- However, because the mass of cells has increased the threshold for negative feedback has also increased.
32
Dexamethasone
An exogenous steroid, so it is used as an analogue for steroids.
33
Action of dexamethasone
If injected in a normal person, low doses should suppress ACTH via negative feedback.
34
Dexamethasone suppression test
- In Cushing's disease: there is no suppression because due to the pituitary adenoma and the mass of the cells growing, the threshold to reach the negative feedback limit has also increased. A higher dose, however, should lead to suppression because the threshold has been reached.
- In an ectopic source of ACTH, there will be no suppression during both the higher and the lower dose. This is because the tumour must be somewhere else such as in the lungs and has nothing to do with the pituitary gland.
- In an adrenal tumour, at a low dose, there is no suppression and at a higher dose, there is suppression also.
35
Adrenocortical insufficiency: Primary adrenocortical failure
Example: Addison's disease is typically autoimmune.
- The adrenal cortex stops functioning and therefore, there is no production of both cortisol and aldosterone which leads to primary adrenal failure.
36
Adrenocortical insufficiency: Secondary
- If there is impaired ACTH release such as during heat trauma, tumour, surgery or steroid withdrawal.
- The biggest symptom of Addison will be hypotension
- There will be high ACTH due to no negative feedback.
37
Use of dynamic tests of adrenal function
This assesses the ability of adrenal glands to produce cortisol in response to ACTH.
38
Short synacthen test
- Measure baseline cortisol at 9am and 30mins after 250ug of synacthen.
- In a normal person, this should lead to the production of cortisol.
- So if the cortisol level increases to more than 200nmol/L then adrenal insufficiency can be excluded.
39
Long synacthen test
- The adrenal cortex shuts down if there is no ACTH production overtime.
- And therefore, in secondary adrenal insufficiency, a 3-day stimulation with synacthen is done.
- And if the levels do not increase it is present.
