Tests Used in Endocrinology

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Thyroid Function Tests

Overview

Thyroid function tests (TFTs) mainly measure free thyroxine, (free T4, FT4) and thyroid-simulating hormone (TSH). Free triiodothyronine (free T3, FT3) is sometimes also measured, however, FT3 is generally elevated if FT4 is elevated, so it is not usually measured.

Since FT4 and FT3 exert negative feedback on the anterior pituitary gland, TSH is reduced when FT4 and FT3 levels are high.

It is helpful to look at TSH first when interpreting TFTs:

  • If TSH is low – high levels of FT4 and FT3 may be suppressing its release, so hyperthyroidism may be likely
  • If TSH is high – low levels of FT4 and FT3 may be not be suppressing its release enough, so hypothyroidism may be likely

TFT patterns

  • Hyperthyroidism – low TSH, high FT4
    • FT3 thyrotoxicosis may occur, where TSH is low, FT4 is normal, but FT3 is high
  • Subclinical hyperthyroidism – low TSH, normal FT4 and FT3
  • Primary hypothyroidism – high TSH, low FT4
    • ‘Primary’ – disorder is within the thyroid gland itself (e.g. autoimmune thyroiditis)
  • Secondary hypothyroidism – low TSH, low FT4
    • ‘Secondary’ – disorder is outside the thyroid gland (e.g. hypopituitarism)
  • Subclinical hypothyroidism – low TSH, normal FT4 and FT3
  • Sick euthyroid syndrome – TSH low, FT4 low or TSH normal, FT4 low
  • Poor compliance with levothyroxine – TSH high, FT4 normal
  • Corticosteroid use – TSH low, FT4 normal

Radioactive Iodine Uptake Test

Overview

Also known as nuclear scintigraphy or a nuclear medicine thyroid scan, a radioactive iodine uptake test involves the patient swallowing or being given an injection of radioactive iodine which emits gamma rays. A gamma camera detects emitted gamma rays from the radioactive iodine. This test gives functional information about the thyroid gland.

Radioactive iodine uptake tests must be avoided in pregnant people.

Findings

  • Grave’s disease – diffuse high uptake
  • Toxic multinodular goitre/adenoma – focal areas of high uptake
  • Thyroid cancer – ‘cold’ areas (areas of abnormally low uptake) 

Dexamethasone Suppression Test

Administering dexamethasone should lead to decreased cortisol secretion due to negative feedback on the hypothalamus and pituitary gland. This negative feedback should lead to reduced cortisol-releasing hormone (CRH) from the hypothalamus and ACTH from the pituitary, leading to low cortisol levels.

The dexamethasone suppression tests are based on this principle and help to localise where the problem is. There are two tests used:

  • Low-dose dexamethasone suppression test – done first to screen for Cushing’s syndrome:
    • Cortisol suppressed (low) – normal
    • Cortisol not suppressed (high/normal) – Cushing’s syndrome
  • High-dose dexamethasone suppression test:
    • This is done if the low-dose test shows Cushing’s syndrome may be present
    • Cortisol suppressed and ACTH suppressed – Cushing’s disease
    • Cortisol not suppressed but ACTH suppressed – adrenal adenoma
    • Cortisol not suppressed and ACTH not suppressed – ectopic ACTH

ACTH Stimulation Test

Overview

The ACTH stimulation test (also known as the short Synacthen test) measures the adrenal gland’s response to adrenocorticotropic hormone (ACTH), which normally stimulates the release of cortisol.

Synthetic ACTH is injected and plasma cortisol is measured before and 30 minutes after. In primary adrenal insufficiency, serum cortisol is usually <500 nmol/L and fails to rise.

Glycosylated haemoglobin (HbA1c)

Overview

Glycosylated haemoglobin (HbA1c) is used as a long-term measure of blood glucose concentration control in people with diabetes mellitus. HbA1c is produced due to the attachment of glucose to red blood cells. It is generally thought to reflect the blood glucose over the last 3 months (as the lifespan of red blood cells is around this time).

Implications

Since HbA1c depends on the red blood cell lifespan, some conditions can interfere with its measurement:

Water Deprivation Tests

Overview

Also known as the desmopressin stimulation test, the water deprivation test involves depriving a patient of water (e.g. up to 8 hours) and measuring urine osmolality (the concentration of solutes in their urine). If urine osmolality is low (the urine is dilute), synthetic antidiuretic hormone (ADH, desmopressin) is given and urine osmolality is measured 2-4 hours after.

Findings

  • Cranial diabetes insipidus:
    • Post-deprivation – urine osmolality is low (due to impaired ADH release)
    • Post-desmopressin – urine osmolality is high (as ADH has now been given)
  • Nephrogenic diabetes insipidus:
    • Post-deprivation – urine osmolality is low
    • Post-desmopressin – urine osmolality is still low
    • Despite ADH still being produced, the kidneys do not respond to it 
  • Primary polydipsia:
    • Post-deprivation – urine osmolality is high – this is normal and ADH is still being secreted and is functional

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