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Y2 Clinical Pathology > Investigating the Endocrine System > Flashcards

Investigating the Endocrine System Flashcards

1
Q

What is a hormone?

A

hormones are messenger molecules secreted by endocrine glands

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2
Q

What is meant by endocrine, paracrine and autocrine signalling?

A

endocrine:

  • endocrine cells release hormones that act on distant cells in the body
  • the hormones travel in the bloodstream

paracrine:

  • the signalling cell induces changes in nearby cells

autocrine:

  • a cell secretes a hormone that binds to autocrine receptors on the SAME cell to induce changes within the cell
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3
Q

What types of cells can hormones influence?

What types of changes do they produce?

A

hormones circulate and influence other tissues

they produce short- and long-term changes in various cells

a hormone can only influence cells that have specific target receptors for that particular hormone

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4
Q

What are the 3 different types of hormones?

A

peptide hormones:

  • PTH, ACTH, TSH

steroid hormones:

  • testosterone, oestradiol, cortisol

tyrosine-based hormones:

  • thyroxine (T4) and triiodothyronine (T3)
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5
Q

What are the 3 ways in which a steroid hormone can elicit a response?

A
  1. classical model
  2. receptor-mediated endocytosis
  3. signalling through cell-surface receptors
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6
Q

What is meant by the ‘classical model’ that shows how a steroid hormone can elicit a response?

A
  1. steroid hormone dissociates from its plasma carrier porotein and diffuses across the cell membrane
  2. after gaining entry to the cell, the free hormone binds to an intracellular receptor and alters gene transcription
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7
Q

What happens in receptor mediated endocytosis?

A
  1. the steroid hormone, bound to its plasma protein, is brought into the cell via a cell-surface receptor
  2. the complex is broken down inside the lysosome and the free steroid hormone diffuses into the cell
  3. the hormone exerts its action at the genomic level or undergoes metabolism
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8
Q

How does signalling through cell-surface receptors work?

A

1, the steroid hormone alters intracellular signalling by binding to cell-surface receptors

the steroid hormone can exert these effects directly or could alter signalling by blocking the actions of peptide hormones

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9
Q

What is meant by feedback regulation in endocrine systems?

A

feedback loops are used to regulate secretion of hormones in the hypothalamic-pituitary axis

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10
Q

What are the following hormones?

A
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11
Q

Which hormones influence the gonads to produce sex hormones?

A
  • GnRH from the hypothalamus leads to…
  • secretion of LH and FSH in the anterior pituitary
  • these hormones cause the gonads to produce sex hormones
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12
Q

Which hormones from the hypothalamus influence the production of growth hormone?

A

GHRH stimulates growth hormone production

Somatostatin suppresses growth hormone production

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13
Q

What does production of TRH in the hypothalamus lead to?

A

TRH increases the secretion of TSH in the anterior pituitary gland

This travels to the thyroid gland and increases thyroxine production

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14
Q

Which hormones from the hypothalamus influence prolactin secretion?

A

PRH increases prolactin secretion

Dopamine suppresses prolactin secretion

Prolactin travels to the breasts

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15
Q

What is the result of CRH production in the hypothalamus?

A

CRH stimulates the anterior pituitary to secrete ACTH

ACTH stimulates the adrenal cortex to secrete cortisol

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16
Q

What is thyroxine-binding globulin (TBG)?

How can it affect interpretation of thyroid function tests?

A

only the “free” unbound forms of thyroxine are physiologically active

if the level of TBG changes, this results in a change in the level of the free hormones

measurement of total hormone levels can be misleading

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17
Q

What conditions may lead to an increase in plasma TBG concentration?

A
  • genetic causes
  • pregnancy
  • oestrogens (OCP)
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18
Q

What conditions may lead to a decreased plasma TBG concentration?

A
  • genetic causes
  • protein-losing states
  • malnutrition
  • malabsorption
  • acromegaly
  • Cushing’s disease
  • high dose corticosteroids
  • severe illness
  • androgens
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19
Q

What conditions may be seen in the following situations?

A
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20
Q

What test is performed if TSH is decreased or elevated?

A

if TSH testing results are normal, no further testing is performed

if TSH is decreased or elevated, a free T4 test is conducted

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21
Q

What conditions may be suggestive of the following scenarios?

A

decreased TSH level:

  • low free T4 - central hypothyroidism
  • normal free T4 - T3 toxicosis or subclinical hyperthyroidism
  • elevated free T4 - hyperthyroidism

elevated TSH level:

  • low free T4 - hypothyroidism
  • normal free T4 - subclinical hypothyroidism
  • elevated free T4 - TSH secreting tumour
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22
Q

What is T3 toxicosis and what might cause it?

A

a state in which patients have a high level of T3 and low TSH but normal level of T4

it is caused by iodine deficiency

or

the earliest stages of disease caused by a thyroid nodule, multinodular goitre or Graves’ disease

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23
Q

What is meant by subclinical hypothyroidism?

A

an early, mild form of hypothyroidism

only the serum level of TSH from the anterior pituitary gland is a little bit above normal

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24
Q

What hormone leves would be seen in secondary hypothyroidism?

A

NORMAL TSH with a LOW T4

8% of patients have low serum TSH concentrations

84% of patients have normal TSH concentrations

8% have high TSH values

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25
Q

What is meant by “sick euthyroid disease”?

A

a condition in which serum levels of thyroid hormones are low in clinically euthyroid patients with nonthyroidal systemic illness

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26
Q

What is the treatment of sick euthyroid disease aimed at?

A

diagnosis is based on excluding hypothyroidism

treatment is directed towards the underlying illness

thyroid hormone replacement is not indicated

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27
Q

What would thyroid function test results look like in someone suffereing from non-thyroidal illness?

A

patients suffering from non-thyroidal illness may show abnormalities within thyroid function tests, despite being euthyroid

TSH levels may be suppressed ( < 0.1 mU/L) in acute phases

28
Q

In a patient suffering from non-thyroidal illness, what happens to TSH levels after illness?

How about free thyroid hormone levels?

A

TSH levels may transiently rise into the hypothyroid range (< 10 mU/L) in the recovery phase following a period of illness

illness can reduce the levels of TBG or modify its capacity to bind T3 and T4

this increases free thyroid hormone levels

29
Q

When should thyroid function tests be requested in hospitalised/ill patients and why?

A

due to the poor predictive value of thyroid function tests in hospitalised/ill patients, they should only be requested if thyroid dysfunction is suspected

30
Q

In a healthy person, how often should TFTs be repeated?

A

every 3 years

31
Q

How often should TFTs be repeated in monitoring of treatment of hyperthyroidism in Graves’ disease?

A
  • repeated 1-2 months after radioactive iodine
  • if the patient remains thyrotoxic, then biochemical monitoring continues at 4-6 week intervals

OR

  • following thyroidectomy for Graves’s disease (and commencement of levothyroxine)
  • serum TSH is measured 6-8 weeks post-op
32
Q

How often should TFTs be repeated when monitoring treatment for hypothyroidism?

A
  • the minimum period to achieve stable concentrations after a change of dose of thyroxine is 2 months
  • TFTs should not be assessed before this time
  • patients stabilised on longterm thyroxine therapy should have serum TSH checked annually
  • an annual fT4 should be performed in all patients with secondary hypothyroidism stabilised on thyroxine therapy
33
Q

What is involved in an immunoassay?

A

it initially involved polyclonal antibodies and radioisotope labelling

polyclonals were largely replaced by monoclonal antibodies

34
Q

What are the 2 main types of immunoassay used in clinical chemistry?

Why are they widely used?

A
  1. immunometric assays
  2. competitive immunoassays

they are widely used as:

  1. specific due to antibody specificity
  2. senstive and able to measure picomolar concentrations
  3. amenable to automation
35
Q

What is the difference between a competitive and non-competitive assay?

A

competitive:

  • patient’s unlabelled analyte of interest (antigen) competes with a constant amount of labelled similar antigen for a limited amount of specific antibody
  • measures the analyte-unbound sites

non-competitive:

  • excess of labelled antibody towards the analyte of interest (antigen)
  • measures the analyte bound sites
36
Q

What may cause interference in an immunoassay?

A

non-specific interference occurs in lipidaemia and haemolysis

positive interference:

  • caused by cross-linking antibody

negative interference:

  • caused by blocking antibody
37
Q

What is meant by assay interference?

A

analytical interference is the effect of a substance present in the sample that alters the correct value of the result

this may be a substance that alters the measurable concentration of the analyte in the sample or alters antibody binding

38
Q

What are the 2 types of adrenal medullary tumours?

A
  • phaeochromocytoma in adults
  • neuroblastoma in children
39
Q

What is a phaeochromocytoma?

What % are malignant / bilateral?

A

tumour of the neuroendocrine chromaffin cells (mainly in adrenal medulla)

10% in extra-adrenal neuroendocrine cells

10% are malignant

5% are bilateral - especially as part of MEN IIa or IIb

40
Q

What are the clinical features of phaeochromocytoma?

Why do they occur?

A

excessive and often episodic release of catecholamines may result in paroxysmal features

  • hypertension
  • sweating, pallor
  • panic attacks
  • headaches
  • abdominal pain
  • no symptoms
41
Q

Why is it difficult to diagnose a phaeochromocytoma?

A

false negative and false positive results of biochemical tests are not uncommon

42
Q

What are the biochemical tests used to diagnose a phaeochromocytoma?

What are the drawbacks of these tests?

A

plasma metanephrines:

  • unstable so must collect on ice
  • not available in many laboratories
  • sensitivity of 99% and specificity of 89%

24 hour urine fractionated metanephrines:

  • usual problems of 24 hour collections
  • sensitivity of 96-100% and specificity of 94-97%
43
Q

How should patients prepare for the diagnostic tests for phaeochromocytoma?

A
  • stop antihypertensive medication for 24 hours
  • certain drugs cause biological or analytical interference with HPLC measurement
  • pseudoephedrine, tricyclic antidepressants, phenoxybenzamine, calcium channel antagonists
  • if measuring urinary VMA, patient should be on a vanilla-free diet
44
Q

What are the follow up tests involved in diagnosing a phaeochromocytoma?

A

clonidine suppression test:

  • used in patients with suspected phaeochromocytoma and borderline changes in catecholamines or metanephrines

plasma chromogranin A:

  • sensitivity 83%, specificity 96%
45
Q

What types of scans or other tests may be offered as a follow up test for a suspected phaeochromocytoma?

A
  • MRI or CT scan of adrenal glands
  • MIBG scan - to detect extra-adrenal phaeochromocytomas or metastases
  • genetic counselling and screening for MEN mutations in young patients, or those with a family history
46
Q

What is meant by Whipple’s triad?

A

a collection of three criteria that suggest a patient’s symptoms result from hypoglycaemia that may indicate an insulinoma

47
Q

What are the 3 criteria involved in Whipple’s Triad?

A
  1. signs and symptoms of hypoglycaemia
  2. resolution of symptoms once glucose level rises (through consumption)
  3. low plasma glucose level

non - diabetic - < 54 mg/dL

diabetic - < 63 mg/dL

48
Q

What are the symptoms of hypoglycaemia in an adult?

A
  • hunger
  • sweating
  • anxiety
  • paresthesias
  • palpitations
  • tremulousness
49
Q

What are the signs of hypoglycaemia in an adult?

A
  • pallor
  • tachycardia
  • widened pulse pressure
50
Q

What is meant by neuroglycopenia?

A

a shortage of glucose in the brain, usually due to hypoglycaemia

it affects the function of neurones and alters brain function and behaviour

51
Q

What are the symptoms of neuroglycopenia in an adult?

A
  • weakness and fatigue
  • dizziness
  • headache
  • confusion
  • behavioural changes
  • cognitive dysfunction
  • blurred vision and diplopia
52
Q

What are the signs of glycopenia in an adult?

A
  • cortical blindness
  • hypothermia
  • seizures
  • coma
53
Q

What stages are invovled in the differential diagnosis of hypoglycaemia in adults?

A

endogenous causes:

  • either insulin dependent or insulin independent

exogenous causes:

  • therapeutic drugs
  • factitious felonious
  • alcohol toxins
54
Q

What are examples of insulin-dependent endogenous causes of hypoglycaemia?

A
  • insulinoma
  • nesidoblastosis
  • NIPHS
  • insulin antibodies

Reactive:

  • alimentary hypoglycaemia
  • reactive hypoglycaemia associated with type 2 DM
  • idiopathic
55
Q

What are examples of insulin-independent endogenous causes of hypoglycaemia?

A

critical organ failure:

  • hepatic diseases
  • cardiac failure
  • renal failure

sepsis

hormone deficiency:

  • cortisol
  • growth hormone
  • hypopituitarism

insulin receptor antibodies

non-islet cell tumour

56
Q

What types of therapeutic drugs act as an exogenous cause of hypoglycaemia?

A

direct effect:

  • insulin
  • sulfonylureas
  • quinine
  • disopyramide
  • B2-adrenoreceptor agonists
  • pentamidine

drug interactions with insulin or sulfonylurea:

  • biguanides
  • PPARy agonists
  • B-adrenoreceptor blockers
  • ACE inhibitors
57
Q

What is an insulinoma?

In which groups is the highest incidence seen?

A

the most common tumours arising from the islets of Langerhans

highest incidence is between 40-60 years

more common in females

58
Q

How is insulinoma diagnosed?

A

a simple fasting blood test

  • low blood sugar (less than 2.2 mmol/l)
  • high insulin (6 microunits/ml or higher)
  • high levels of C peptide (0.2 nmol/l or higher)
59
Q

What are the features associated with Cushing’s syndrome?

A

obesity:

  • moon face
  • central obesity

skin:

  • thin skin
  • purple striae
  • easily bruised
  • hypertension
  • glucose intolerance
  • menstrual disturbances and impotence
  • thin limbs and muscle weakness
  • back pain due to osteoporosis
  • psychiatric disturbances - depression / psychoses
60
Q

Label the components of the hypothalamic-pituitary-adrenal axis

A
61
Q

Where is cortisol produced?

What can influence this process?

A

cortisol is produced in the zona fasciculata of the adrenal gland

the release of cortisol is controlled by the release of ACTH from the pituitary gland

62
Q

What is the difference between primary and secondary cortisol excess?

A

primary cortisol excess:

  • associated with disorders of the adrenal glands
  • does not depend on stimulation from ACTH
  • e.g. adrenal adenoma

secondary cortisol excess:

  • adrenal hyperfunction due to an excess of adrenocorticotropic hormone (ACTH)
63
Q

What conditions is ectopic ACTH secretion commonly associated with?

A
  • benign carcinoid tumours of the lung
  • small cell tumours of the lung
  • islet cell tumours of the pancreas
  • medullary carcinoma of the thyroid
  • tumours of the thymus gland
64
Q

What is the difference between primary and secondary disorders affecting the thyroid?

A

primary thyroid disease:

  • due to disease within the thyroid gland
  • in primary hypothyroidism, TSH levels are high but the thyroid gland does not respond

secondary thyroid disease:

  • due to pituitary or hypothalamic disease
  • in secondary hypothyroidism, TSH levels are low
65
Q

What are the principles of dynamic investigations of thyroid function?

Why are random hormone values not used?

A

excess production:

  • can it be suppressed?

insufficient production:

  • can it be stimulated?

random hormone values can be identical in either circumstance

66
Q
A

Y2 Clinical Pathology (76 decks)

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