Growth hormone deficiency

The diagnosis of adult growth hormone deficiency requires the presence of symptoms as well as a failure of GH to rise appropriately after an insulin or other appropriate stimulation test.

Baseline investigations - all patients

Full blood count

Useful indicator of general health and underlying disease. 

Normocytic normochromic anaemia and eosinophilia may be seen with glucocorticoid deficiency.

Urea and electrolytes

Useful indicator of general health and underlying disease.

Hyperkalaemia and hyponatraemia may occur in glucocorticoid deficiency.

Liver function test

Useful indicator of general health and underlying disease.

Also needed as baseline before starting medical treatments.

HbA1c, fasting glucose and lipids

Hypopituitary patients have an elevated mortality due to an excess of cardiovascular deaths.

Fasting glucose and lipids are essential for cardiovascular risk modification and require aggressive management. HbA1c should also be documented before starting GH therapy.

Bone profile

Hypercalcaemia may occur with glucocorticoid deficiency or with thyrotoxicosis, although this is rarely encountered in pituitary patients.

Hypercalcaemia in a pituitary patient should prompt consideration of undelying multiple endocrine neoplasia type 1.

AGDA questionnaire

The QOL-AGHDA score provides and objective quantification of the symptoms of adult GH deficiency.

Further investigations - selected cases only

Baseline pituitary function


Prolactin

It is essential to urgently test serum prolactin in a patient with an apparent non-functioning pituitary adenoma, in case this actually represents a macroprolactinoma.

Elevated prolactin also occurs with non-functioning tumours due to loss of dopaminergic inhibition.


9am cortisol

Ensure patients have stopped sex steroid therapy, for example HRT or the combined oral contraceptive pill for six weeks prior to test.

Estrogen replacement therapy leads to elevation of cortisol binding globulin and hence serum cortisol and so is difficult to interpret. 

Due to the circadian rhythm of ACTH release, cortisol is best assessed early morning (or on waking in patients with irregular hours, for example shift workers).

Levels above 590nmol/l exclude glucocorticoid deficiency.

Patients with levels below 590nmol/l with pituitary disease, especially at presentation, or in patients with prior radiotherapy will require formal assessment for ACTH reserve, for example with an insulin stress test or glucagon test.


Thyroid stimulating hormone, free thyroxine

It is essential to assess levels of both thyroxine and thyroid stimulating hormone (TSH) in pituitary patients since a normal TSH level is frequently associated with loss of thyroid function in this patient group.

Levels of both TSH and thyroxine are typically low-normal in hypopituitary patients.

Ideal replacement therapy is reflected by a serum thyroxine level between the middle and the upper end of the reference range.


Insulin like growth factor I

Very low IGF-I levels alone are not diagnostic for GH deficiency but are a useful screen mandating a formal GH provocation test, for example insulin stress test or glucagon test, in patients with pituitary disease especially in the presence of suggestive symptoms.


Luteinising hormone, follicle stimulating hormone

In the presence of pituitary disease both luteinising hormone and follicle stimulating hormone are typically low, or not elevated, in post menopausal women.


Estriodiol, testosterone, sex hormone binding globulin

Testosterone should be assessed early morning on at least two occasions, and in conjunction with sex hormone binding globulin in order to calculate free androgen index before committing to long term replacement therapy.

MRI pituitary

This should be performed in all cases with documented abnormality of pituitary function and urgently at presentation if there is visual field loss or optic disc pallor.

MRI needs to be repeated prior to starting GH therapy, and repeated after 12 months treatment as routine disease surveillance.

Electrocardiogram

This is required prior to performing an insulin stress test.

Prostate specific antigen

PSA should be tested in all male patients being considered for testosterone replacement therapy and annually thereafter.

Insulin stress test

This should be performed if GH or ACTH deficiency is suspected but not yet confirmed subject to the usual safety exclusion criteria.

Arginine-GHRH testing

If the patient cannot tolerate insulin stress testing, arginine-GHRH testing should be performed, as this is the next most specific test of GH reserve. 

Glucagon test

Glucagon test should be performed if GH or ACTH deficiency is suspected but not yet confirmed and the patient is unable to tolerate an insulin stress test, and an arginine-GHRH test is not available.

Bone densitometry

Bone mineral density should be assessed where there is clinical suspicion of osteoporosis, in patients with previous excessive glucocorticoid replacement, in patients with long standing gonadotropin deficiency, or in patients with GH deficiency.

Vitamin D levels

In patients with known or suspected osteoporosis, serum vitamin D levels will guide whether routine calcium and vitamin D supplementation is enough, or whether specific high dose vitamin D replacement is required.