Laboratory Investigation of Endocrine Disorders Flashcards
- Explain the hypothalamic pituitary thyroid axis?
- Thyrotrophin releasing hormone (synthesised in the pituitary and released into the hypophyseal system) causes TSH release which controls the synthesis and release of TH.
- TH are synthesised in the thyroid via series of enzyme catalysed reactions, beginning with uptake of iodine into gland.
- T4 main hormone secreted by thyroid, T3 is more biologically active – mostly formed by peripheral enzyme conversion from T4.
- Is TH under positive or negative feedback?
Negative feedback
circulating TH , causes the hypothalamus to release less TRH->TSH->TH
- What are Thyroid Hormones essential for?
normal growth and development; they increase basal metabolic rate (BMR) and affect many metabolic processes.
- How are the effects of thyroid hormone mediated?
•Effects are mediated via activation of nuclear receptor.
- What is the Total and free amount of T4? in the serum?
Total : 60-150 nmol/L
Free : 11-23 pmol/L
- What % of both T4 and T3 are protein bound?
T4= 99.98
T3=99.66
- What is pmol/L
How do you convert between nmol and pmol?
Picomoles per liter (pmol/L)
1 nmol/L= 1000 pmol/L
- What is the Total and free amount of T3? in the serum?
Total = 1.0-2.9 nmol/L Free = 4-8 pmol/L
- What is the half life of both T4 and T3?
T4= 6-7 Days T3= 0.5-1 Days
- What is :
- Euthyroid
- Hypothyroid
- Hyperthyroid
Euthyroid = Normal range of T3 and T4
Hypothyroid = Low levels of T3 and T4
Hyperthyroid = High levels of T3 and T4
- What is the difference between primary and secondary hypo/hyper thyroidism
Primary = Dysfunction in the thyroid gland
Secondary = Dysfunction is with pituitary or hypothalamus (tertiary)
- What is Hyperthyroidism ?
Excessive production of thyroid hormones (thyrotoxicosis)
- What are the clinical features of hyperthyroidism?
oGraves: weight loss, heat intolerance, palpitations, goitre (neck swelling), eye changes (Graves).
oThyroid storm in extreme cases: dangerously high HR, BP and body temperature.
- What are some causes of hyperthyroidism?
Graves disease (most common): due to stimulatory TSH-R antibodies
oToxic multinodular goitre: thyroid nodules (don’t require TSH) produce excess thyroid hormones.
oToxic adenoma: single nodule produces the hormone.
oSecondary: excess TSH production (rare)
- What is hypothyroidism?
Deficient production of thyroid hormones
- What are the clinical features of hypothyroidism?
o weight gain, cold intolerance, lack of energy, goitre(swelling of the thyroid gland )
o congenital - developmental abnormalities due to reduced TH from birth.
- How do you know if hypothyroidism is primary or secondary?
oRaised TSH, reduced T4 suggests primary failure.
oReduction in TSH and T4 suggests secondary (hypopituitarism).
- What are some causes of hypothyroidism?
oAutoimmune thyroiditis (Hashimoto’s) - Thyroid peroxidase antibodies (anti-TPO) so less TH produced.
oIodine deficiency e.g. certain mountainous regions.
oToxic adenoma
oSecondary – lack of TSH
19. Case study: A 48 year-old woman presented to her GP with palpitations, weight loss and heat intolerance. A serum sample gave the following results: Free T4: 31 pmol/L (11-23) Free T3 : 12 pmol/L (3-8.8) TSH : 0.08 mU/L (0.5-4.0) Diagnosis?
-Hyperthyroidism
20. Case Study: A 70 year old man complained of tiredness and weight gain. His heart rate was 55 beats/min. Thyroid function tests were carried out: Free T4 :10 pmol/L (11-23) TSH : 18.4 mU/L (0.5-4.0) Diagnosis?
Primary hypothyroidism
- Blood flows from the outer adrenal cortex to where?
•Blood flows from outer cortex (steroids e.g. mineralocorticoids, glucocorticoids, and androgen) to inner medulla (adrenaline and noradrenaline).
- What impact do layer-specific enzymes have on steroid synthesis?
•Layer-specific enzymes mean steroid synthesis in one layer can inhibit different enzymes in subsequent layers–> functional zonation of cortex (diff hormones made in each layer)
- What hormones are made in the :
- Zona Glomerulosa
- Zona Fasciculata
- Zona Reticularis
Zona Glomerulosa = Mineralocorticoids
Zona Fasciculata = Glucocorticoids
Zona Reticularis = Androgens
- How are steroids of the adrenal cortex transferred from outside to inside ?
Via Capillary Network
- Fill in the blank:
“Enzymatic modification of ** allows the production of different steroids”
Cholesterol
- Following questions are about Mineralocorticoids:
- Give an example of one
- What are they involved in
- What is the synthesis and release regulated by?
e.g. aldosterone
salt and water balance in order to maintain plasma volume by sodium retention: maintenance of blood pressure over the long term (by maintaining blood volume).
oSynthesis and release regulated by hypothalamic-pituitary-adrenal axis (CRH, ACTH)
- Following questions are about Glucocorticoids:
- Give an example of one
- What are they involved in
- What is the synthesis and release regulated by?
e.g. cortisol
involved in metabolism and immune function and controlled by RAAS.
oStress increases release, but minimal levels essential for normal function.
- What are androgens secreted in response to?
ACTH
- What are the main effects cortisol has on the CVS?
maintains blood pressure by counter-balancing NO
- What effect does cortisol have on insulin resistance?
promotes insulin resistance in skeletal muscle to preserve glucose for other essential tissues e.g. brain, promotes gluconeogenesis and lipolysis etc.
- What causes insulin secretion and lipogenesis?
Hyperglycaemia
- What type of receptor is ACTH?
G-protein couples
- What does the ACTH receptor stimulate the uptake of ?
via cAMP stimulates cholesterol uptake and steroid synthesis
- What syndrome is associated with:
- Aldosterone Excess
- Cortisol Excess
- Aldosterone excess: Conn’s syndrome.
* Cortisol excess: Cushing’s syndrome.
- What is the synthesis and release of:
Cortisol
Aldosterone
Adrenal Androgens
regulated by?
Cortisol: synthesis and release regulated by hypothalamic-pituitary-adrenal axis (CRH, ACTH)
Aldosterone: controlled by RAAS
Adrenal androgens: ACTH (not gonadotropins)
- Explain the feedback system for cortisol?
•Exogenous glucocorticoid negatively feedback to the hypothalamus and pituitary which reduces cortisol production.
- How is the feedback loop of cortisol disturbed in cushings syndrome (`excess cortisol)
•Raised ACTH from pituitary adenoma causes raised increased cortisol production which feedbacks to the hypothalamus and anterior pituitary to reduce CRH but ACTH remains being produced—> increased cortisol
- What is Dexamethasone?
Dexamethasone is a steroid that prevents the release of substances in the body that cause inflammation
- What is A Dexamethasone (exogenous synthetic glucocorticosteroids) Suppression Test - how can we interpret the results
•Low doses will normally suppress ACTH secretion via negative feedback.
•LOW dose fails to suppress ACTH secretion with pituitary disease (Cushing’s) as it’s not enough for the new higher negative feedback threshold, but
.Higher dose will suppress ACTH secretion in Cushing’s.
•No suppression with low or high dose: suggests ectopic source of ACTH (e.g. secondary tumour).
- If you conduct a LOW dose dexamethasone suppression test , what result (ie suppression or not) would you expect in :
- Cushing’s disease
- Adrenal Tumour
- Ectopic ACTH
- Cushing’s disease = No suppression
- Adrenal Tumour= No suppression
- Ectopic ACTH= No suppression
- If you conduct a HIGH dose dexamethasone suppression test , what result (ie suppression or not) would you expect in :
- Cushing’s disease
- Adrenal Tumour
- Ectopic ACTH
Cushing’s disease=Suppression
Adrenal tumour = No suppression
Ectopic ACTH =No suppression
- What level of plasma ACTH would you expect in :
- Cushing’s disease
- Adrenal Tumour
- Ectopic ACTH
- Cushing’s disease = High
- Adrenal Tumour = Low
- Ectopic ACTH = Very high
- What is Addison’s disease?
- Primary adrenocortical failure - usually autoimmune
* Loss of cortisol, androgens and aldosterone and High ACTH.
- What is secondary adrenocortical insufficiency ?
impaired ACTH release: Head trauma, tumour, surgery, Abrupt steroid withdrawal.
- What are we testing for in adrenal function tests?
•Assess ability of adrenal to produce cortisol in response to ACTH.
- How does the short synacthen (synthetic ACTH) test work?
oMeasure baseline cortisol (9am) and 30 min after 250 µg synacthen (synthetic ACTH) i.m.
o Adrenal insufficiency is excluded by an increase in cortisol of >200 nmol/L and/or a 30 min value >550
- How does the long synacthen (synthetic ACTH) test work?
o Adrenal cortex ‘shuts down’ in absence of stimulation by ACTH – time needed to regain responsiveness
o 3-day stimulation with i.m. synacthen
o In secondary (but not primary) adrenal insufficiency cortisol increases by >200 nmol/L over baseline
o Long test not often necessary since ACTH assay can distinguish.
- o A 51 year old woman was admitted to hospital with a history of weight loss and lethargy. She reported that she felt dizzy when she stood up.
o Biochemical tests revealed that she was hyponatraemia and she was given i.v. saline.
o A synacthen test was carried out with the following results:
o Baseline cortisol 342 nmol/L (ref. range150-650)
o 30 min post synacthen. 419 nmol/L
o How would you interpret these results? What further tests should be carried out?
Her cortisol levels should have increased by 200 or at least been 500 in total
It wasn’t
This suggests the adrenal cant produce cortisol in response to ACTH -> Should take the long synacthen test to confirm adrenal insufficiency
