Investigations
1st investigations to order
serum insulin-like growth factor 1 (IGF-1)
Test
Blood levels are stable throughout the day, as IGF-1 has a long half-life of around 15 hours. It is the recommended screening test for acromegaly and is needed to confirm the diagnosis.[12]
The assay used should have adequate sensitivity, specificity, and reproducibility (this varies in different laboratories). The result must be interpreted with age- and sex-normative data.
Malnutrition, hypothyroidism, systemic diseases with catabolic states, liver failure, and exogenous oestrogen alter IGF-1 concentrations.
In adolescence and pregnancy, IGF-1 levels are physiologically elevated.
Result
elevated
oral glucose tolerance test (OGTT)
Test
OGTT is indicated in patients with mildly elevated IGF-1 concentrations. It is not required if IGF-1 is very elevated and the patient has clear cut features of growth hormone (GH) excess.[4] A lack of suppressed GH during an OGTT (with 75 g glucose load) confirms the diagnosis of acromegaly.[12]
With glucose loading, false positive results (failure of GH suppression) can occur in patients with diabetes mellitus, hepatic or renal insufficiency, or anorexia nervosa, and in adolescents. A false negative response to glucose loading may be seen in some patients with acromegaly and only a mild degree of GH hypersecretion.[15]
Result
nadir GH value >0.4 or 1 microgram/L (>1 nanogram/mL) (depending on the assay used)
random serum growth hormone (GH)
Test
Because GH values vary significantly during the day for normal people, an isolated elevated value does not, in itself, provide evidence for the presence of acromegaly. A lack of reliable assays, assay standardisation, and adequate normative data also limits interpretation. Therefore, the use of random GH levels to diagnose acromegaly is not recommended.[12]
GH levels in normal subjects are generally <1 microgram/L (<1 nanogram/mL) with a few bursts of secretion during the day when GH levels increase up to 30 micrograms/L (30 nanograms/mL), overlapping with values seen in acromegaly. GH concentrations in patients with active acromegaly rarely drop to <1 microgram/L (<1 nanogram/mL).[12]
Result
an elevated random GH level is suggestive of acromegaly; however, single random GH measurements are not recommended
pituitary MRI or CT scan
Test
Gadolinium-enhanced MRI of the pituitary can detect small microadenomas (<10 mm diameter) and define the extent of macroadenomas (>10 mm diameter).
The sensitivity for macroadenomas is 100% and is also high for microadenomas >5 mm in diameter.
Smaller adenomas may be missed.
As 20% of the normal population harbour pituitary microadenomas, the specificity of this imaging is reduced.[20]
Result
characteristic features of pituitary adenoma
Investigations to consider
GH-releasing hormone
Test
Neuroendocrine tumours (various body locations) can secrete excess GH-releasing hormone and/or GH.
Result
elevated in ectopic GH-releasing hormone secretion
chest and/or abdominal CT scanning
Test
Could be used prior to octreoscan to locate source of ectopic GH/GH-releasing hormone production.
Result
tumour localisation
total body scintigraphy with radio-labelled somatostatin analogue (octreoscan)
Test
Performed with suspected acromegaly due to ectopic sources of hormone production.[12]
Locates the tumour and demonstrates somatostatin receptor expression by the tumour.
Result
tumour localisation
PET scan with radio-labelled somatostatin analogue (Gallium-68 DOTATATE)
Test
Performed with suspected acromegaly due to ectopic sources of hormone production.[19]
Locates the tumour and demonstrates somatostatin receptor expression by the tumour.
Result
tumour localisation
plasma cortisol
prolactin
thyroid-stimulating hormone (TSH) and free thyroxine
estradiol or testosterone
visual field testing
Test
Recommended as part of baseline testing in all patients with acromegaly.[12]
Result
may show deficit if large tumour compressing the optic chiasm
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