Investigation of Disease - Endocrine Flashcards
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?
Stimulus: - 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?
Acromegaly
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?
Syndrome:
Describes symptoms of cortisol excess
- Could be due to hyperexcretion of ACTH that causes cortisol overproduction, or just cortisol hyperecretion
Disease:
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?
Hypothalamus: 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
What are the symptoms of diabetes?
Polyuria
Polydispia
Weight loss (although obesity predisposing factor for type 2)
Fatigue
What are the 2 WHO defined criteria for diabetes diagnosis?
- Random plasma glucose > 11.1 mmol/L with symptoms
- Fasting plasma glucose > 7.0 mmol/L on 2 occasions
- Oral glucose tolerance test
What are the standard patient preperations for the oral glucose tolerance test (OGTT)?
- Normal carbohydrate intake for 3 days before test
- fasting (water only) for 8-14 hours before test
- no smoking before or during test
What is the standardised test protocol for OGTT?
- Fasting venous plasma glucose sample
- 75g glucose in 200mL water drunk in 5 minutes
- Immediately followed by 100mL water
- No smoking, exercise,eating during test
- Venous plasma glucose sample at exactly 2 hours after glucose load
What is the fasting plasma glucose conc and 2 hour plasma glucose conc of a healthy and diabetic individual?
Normal
Fasting - 7 mmol/L
2 hour - equal to or >11.1 mmol/L
What are the long term complications of diabetes?
- Hyperglycemia can lead to excessive non-enzymatic glycation of several molecules e.g haemoglobon forming HbA1C
- Other soluble proteins, lipoproteins and structural proteins can be glycated and transformed into pro-inflammatory molecules called advanced glycation end-products (AGEs)
- AGEs can bind to receptors (RAGEs) on targer cell especially vascular endothelium promoting vascular inflammation and cardivascular risk
Increased incidence of macrovascular disease (heart attack, stroke)
Increases incidence of microvascular disease (nephropathy, neuropathy)
What is the HbA1c test used for and what does it test for?
Indicates your blood glucose levels for the previous two to three months.
Measures the amount of glucose that is being carried by the red blood cells in the body.
What are the target values in HbA1c testing?
between 6.5% (48 mmol/L) and 7.5% (58 mmol/L) as this is proven to decrease risk of developing microvascular complications
What is the hypothalamic-pituitary thyroid axis?
Hypothalamus secretes thyroid releasing hormone (TRH)
Anterior pituitary produces TSH
Thyroid gland produces triiodothyronine (T3) and thyroxine (T4)
T3 and T4 have negative feedback on anterior pituitary and hypothalamus
What are thyroid hormones required for?
- Regulate basal metabolic rate (disorders result in altered cellular metabolism)
- Required for normal physical and mental development
What are the symptoms of hypothyroidism?
Reduced metabolic rate:
- weight gain
- slowing of activity
- slower heart rate
- cold intolerance
What are the symptoms of hyperthyroidism?
Increased metabolic rate: Weight loss Anxiety Muscle weakness Heat intolerance
What are the main 3 diseases associated with hypothyroidism?
Hashimoto’s disease
Congenital hypothyroidism
Anterior pituitary tumour
Describe for Hashimotos disease, the cause, whether it is a primary or secondary problem and the resulting concentrations of T3, T4, TSH and TRH
Cause:
Autoimmune disease, destruction of thyroid gland
Primary disorder
Low T3 and T4, high TSH and TRH
Decrease due to gland destruction, lack of negative feedback from T3 and T4 causes increase in TSH/TRH but no impact on thyroid gland
Describe for congenital hypothyroidism, the cause, whether it is a primary or secondary problem and the resulting concentrations of T3, T4, TSH and TRH
Cause:
Lack of gland or defect in gland at birth
Primary condition
Decrease due ineffective gland or lack of, lack of negative feedback from T3 and T4 causes increase in TSH/TRH but no impact on thyroid gland
Describe for an anterior pituitary tumor, the result in hormone production, whether it is a primary or secondary problem and the resulting concentrations of T3, T4, TSH and TRH
Result of tumour: Lack of TSH synthesis Secondary problem Low T3, T4 and TSH, High TRH Lack of negative feedback from H2 and H3 increases H1 but no impact on AP
How can tests distinguish between the 3 hypothyroidism diseases?
Levels of TSH and thyroid hormones can be measured to give an indication of whether the problem is primary or secondary
In Hashimotos Disease antibodies to the thyroid gland can also be detected e.g thyroglobulin
What is a TRH test, why would it be done and how is it performed?
A stimulation test to assess whether thyroid hormones are properly regulated
- Can be used to investigate hyper- or hypothyroidism, anterior pituitary function and hypothalamic dysfunction
- Performed by intravenous administration of TRH
- TSH levels measured
What is a normal response in the TRH test, and what response would indicate a secondary or primary problem?
Normal response - TSH goes up
Secondary problem - absent TSH response, no production due to pituitary gland problem
Primary problem - TSH exaggerated response due to lack of negative feedback from T3 and T4
