Abnormal increase in the size of glandular breast tissue in a male patient. The diagnosis is clinical, but investigation is required to determine the underlying cause.

Baseline investigations - all patients

Full blood count

This should be tested prior to and during testosterone treatment because of the risk of polycythaemia developing. Normocytic normochromic anaemia and eosinophilia may be seen with undiagnosed hypopituitarism.


Haemochromotosis may be associated with the development of secondary hypogonadotropic hypogonadism.

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.

Liver function test may be surprisingly normal in cirrhosis.

Albumin levels are required to calculate free androgen index in borderline cases and liver function should also be documented before starting testosterone replacement therapy in all.

Bone profile

Hypercalcaemia may occur with thyrotoxicosis and, rarely, with hypopituitarism, both of which may be associated with gynaecomastia. Hypercalcaemia may also occur with malignancy.

Prostate specific antigen

PSA should be documented before considering testosterone replacement therapy.

Baseline pituitary function

Testosterone, sex hormone binding globulin

Due to their circadian release, sex hormones should be assessed early morning (typically at 9am), and repeated on more than one occasion.

Sex hormone binding globulin is necessary to calculate the free androgen index. This is particularly important where testosterone levels are near normal, and the decision to start testosterone replacement is not clear cut.

Luteinising hormone, follicle stimulating hormone

Where sex hormones are confirmed as low, low or normal luteinising hormone (LH) and follicle stimulating hormone (FSH) indicate pituitary or hypothalamic pathology.

Elevations in LH and FSH indicate gonadal failure, for example secondary to mumps, testicular trauma, surgery or torsion in males.


Hyperprolactinaemia may present with tender gynaecomastia and hypogonadism in male patients.

Multiple medications lead to elevations in serum prolactin, and high levels may also occur in non functioning pituitary adenomas.

Thyroid stimulating hormone, free thyroxine

Thyrotoxicosis may cause gynaecomastia in some patients.

9am cortisol

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 possible pituitary disease and levels below this may require formal assessment for ACTH reserve, depending on clinical suspicion.

Growth hormone, insulin like growth factor I

A normal growth hormone (GH) and insulin like growth factor I (IGF-I) taken together form a useful screen for acromegaly.

Very low IGF-I levels alone are not diagnostic for GH deficiency but are a useful screen indicating potential pituitary dysfunction.

MRI pituitary

This should be performed in all cases with documented hypogonadotropic hypogonadism and urgently if there is visual field loss or optic disc pallor.

Further investigations - selected cases only

MRI olfactory bulbs

MRI should include the olfactory bulbs in patients with suspected Kallmann’s syndrome.

Chest radiograph

All patients presenting with possible malignancy should have a CXR performed at baseline.

Mammography and or breast MRI

Mammography and further imaging should be considered in patients with unilateral gynaecomastia, breast masses, changes to the overlying skin, or any other suspicious features.

Testicular or pelvic ultrasound scan

This is useful to perform in most patients presenting with absent or delayed puberty to identify and locate the gonads.

This is also essential in patients presenting with gynaecomastia with a testicular mass.

Visual perimetry and acuity

Formal visual field testing is mandatory if there is clinical or MRI suspicion of chiasmal impingement in patients with pituitary disease.


This should be performed at presentation in patients with absent puberty and gynaecomastia.

Insulin stress test

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

Glucagon test

Glucagon testing 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.

Arginine-GHRH testing

If insulin stress testing is unavailable or contraindicated, arginine-GHRH testing is a suitable alternative test for GH reserve.

Bone densitometry scan

This should be considered in all patients with long standing hypogonadism. It may be useful to repeat after five years of treatment.

Vitamin D

Low serum vitamin D levels strengthen the case for vitamin D replacement therapy in patients with osteoporosis of any cause.

Tumour markers

Alpha-feto protein and human chorionic gonadotropin should be assessed where testicular or other malignancy is suspected.