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Give an example of a simple endocrine negative feedback reflex

- Low plasma calcium ion concentration
- Parathyroid hormone produced from parathyroid cell
- PTH causes increase in bone resorption, increase in reabsorption of Ca2+ from kidney and production of calcitrol that increases intestinal calcium absorption
- Plasma calcium increases
- Calcium binds to calcium binding receptor on parathyroid cells, causing inhibition of PTH release


What does a 3 cell negative feedback usually consist of?

Usually composed of the hypothalamus, anterior pituitary and a third endocrine e.g. the thyroid or adrenal gland


What are primary, secondary and tertiary hormone defects?

- A defect in the hypothalamus is a tertiary defect
- A defect in the anterior pituitary is a secondary defect
- A defect in the endocrine gland producing the hormone with the biological effect on homeostasis is a primary defect


Describe the 3 different causes for symptoms of hypersecretion

Tertiary problem:
H1, H2 and H3 increased
Negative feedback of H" and H3 have no effect
Secondary problem:
H2 and H3 increased
Negative feedback of H2 causes hypothalamus H1 to decrease but no impact on anterior pituitary
Primary problem:
H3 increased
Negative feedback reduces h1 and H2 but no impact on endocrine gland


Describe the 3 different causes for symptoms of hyposecretion

Tertiary problem:
H1, H2 and H3 decreased
Lack of negative feedback from H2 and H3 does not increase H1 production
Secondary problem:
H2 and H3 decrease
Lack of negative feedback from H2 and H3 increases H1 but no impact on AP
Primary problem:
H3 decreased
Lack of negative feedback from H3 increases H1 and H2 but no impact on endocrine gland


What sample is usually used for hormone measurements?

Blood or urine (blood most common)


What are the units of measurement of hormones and electrolytes and how can a clinician tell if the results are normal?

Units are usually nmol/L (sometimes pico or micro) OR units per litre U/L
Measurement always have a reference interval


What percentage of values found in healthy individuals are included in a reference interval? What problem does this lead to?

95% - 5% of healthy individuals lie outside range and some diseased patients lie in range
Results in false positives and false negatives


Explain the secretion of GH, what causes it and what it then causes?

- Circadian rhythm
- Stress and cortisol
- Fasting
> Causes hypothalamus to secrete GnRH
> Hypothalamic-hypophyseal portal pathway takes GnRH to anterior pituitary, causing it to secrete GH
- GH causes:
> Increase in blood glucose
> Bone and tissue growth
Also causes Liver and other tissue to produce insulin like growth factor (ILGF) which causes:
> Cartilage growth
> Other 2 things above


Why is measuring GH directly not a good method?

Low concentration
Pulsatile secretion


What is measured to determine GH levels?

Increase in glucose
(Dynamic function test for GH)


What is the oral glucose tolerence test (OGTT) and how is it performed?

- A suppression test that should reduce GH levels in a normal patient
- Glucose is administered to make patient hyperglycaemic
- Level of GH is then measured
- Normal adults will suppress GH secretion in response to hyperglyceamia


What is this test commonly used to detect?



What usually causes acromegaly?

An adenoma of the pituitary gland resulting in continuous GH secretion - not controlled by feedback


What is the insulin-induced hypoglycemia test (insulin stress test) used for and how is it performed?

- Used to assess pituitary function
- Hypopituitarism could be caused by tumour preventing the production of hormones
- Stimulation test to prompt the production of GH and adrenocorticotrphic hormone (ACTH)
- ACTH stimulates secretion of cortisol from adrenal cortex
- Insulin administered to produce hypoglycemia


What is measured in the insulin stress test and what do the results suggest?

- Levels of GH and cortisol are measured
- Normal adults will secrete extra GH and cortisol to combat the fall in glucose
- Decreased hormone response may be indicator of disease e.g hypothyroidism


What causes Cranial Diabetes Insipidus and what are the symptoms?

Underproduction of ADH in the posterior pituitary gland
- Polyuria - excess dilute urine (up to 20L in 24 hours)
- Polydipsia - excessive thirst


What occurs to the osmolality of the plasma and urine in DI?

High plasma osmolality
Low urine osmolality


What are the causes of CDI?

- Familial (rare)
- Acquired:
> Tumour
> Trauma (severe head injury)
> Infection e.g meningitis


What is nephrogenic diabetes insipidus?

ADH is produced, but not recognised by the nephrons of the kidneys


What is osmolality?

The concentration of a solution expressed as the total number of solute particles per kilogram.


What is the water deprivation test and how is it performed?

- Test for DI and 2 distinguish between the 2 types
- Patient denied water for 7 hours
- Plasma and urine osmolality measured
- Patients urine should become more concentrated due to ADH action
- Urine osmolality remains inappropriately low in DI patients


What is desmopressin and how is it used in the water deprivation test to distinguish between the 2 types of DI?

Desmopressin is an ADH analogue
Administered at 7 hours
Cranial DI patients will respond - increased urine osmolality
Nephrogenic DI patients will not respond - dilute urine remains


What is Cushing's Syndrome and what is Cushing's Disease?

Describes symptoms of cortisol excess
- Could be due to hyperexcretion of ACTH that causes cortisol overproduction, or just cortisol hyperecretion
Refers to a specific cause of Cushing's Syndrome - a tumour of the anterior pituitary gland


Cushling's disease is a 3 cell endocrine system. What are the 3 glands involved and what are H1,2&3?

H1 - corcitotrophin releasing hormone (CRH)
Anterior pituitary
H2 - Adrenocorticotrophic hormone (ACTH)
Adrenal cortex
H3 - cortisol


Is Cushing's Disease a primary, secondary or tertiary problem and explain why

Secondary problem
H2 and H3 increase
Negative feedback of H2 and H3 on hypothalamus decreases H1 but no impact on H2 secretion due to tumour


What 2 methods are used to distinguish Cushing's Disease as the cause of Cushing's syndrome?

1) Measure levels of cortisol, ACTH and CRH
- Relative levels wouls show whether a secondary or primary problem
- Complicated by episodic ACTH release, cortisol BP in plasma etc
2) Use a dynamic function test to see how the regulation of cortisol production is affected
- Dexamethasone Suppression Test - uses large amounts of cortisol analogue to try and suppress cortisol production


What occurs in the dexamethasone supression test and what do the results indicate?

- Dexamethasone administered over 6 days
- Day 1-2 control
- Day 3-4 0.5mg 4times/day
- Day 5-6 2mg 4times/day
(increasing dose)
Normal - supression of cortisol even at lose dose
Secondary cause - no response at low dose, some sensitivity retained at high dose (high dose suppression)
Primary cause - No suppression at all, at high or lose dose


What is the global growth of diabetes (mellitus) from 1985 to 2005?

1985 - 30 million
2005 - 217 million


What is the cause of diabetes?

Absolute or functional deficiency in circulating insulin resulting in an inability to transfer glucose into tissues where it is needed