Loss of gonadal function of any cause. Diagnosis requires testing of sex hormone and gonadotropin levels. This section includes absent or delayed puberty, primary testicular failure, premature ovarian failure, and secondary hypogonadotropic hypogonadism.
Baseline investigations - all patients
Full blood count should be tested prior to testosterone treatment.
Normocytic normochromic anaemia and eosinophilia may be seen with glucocorticoid deficiency.
Haemochromotosis may be associated with the development of secondary hypogonadotropic hypogonadism.
Useful indicator of general health and underlying disease.
Hyperkalaemia and hyponatraemia may occur in glucocorticoid deficiency.
Liver function test may be surprisingly normal in cirrhosis.
Albumen 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.
Useful indicator of general health and underlying disease.
Hypercalcaemia may occur with glucocorticoid deficiency.
Hypopituitary patients have an elevated mortality due to an excess of cardiovascular deaths.
Fasting glucose and lipids are essential for cardiovascular risk modification.
PSA should be documented before considering testosterone replacement therapy.
Due to their circadian release, sex hormones should be assessed early morning (typically at 9am) and on more than one occasion. In women, this should ideally be performed in the early follicular phase and off any interfering medication, for example the contraceptive pill.
Sex hormone binding globulin is necessary to calculate free androgen index in some cases, for example where the decision to start testosterone replacement is not clear cut.
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 primary or auto-immune ovarian failure, or secondary to mumps or testicular trauma in males.
Hyperprolactinaemia frequently presents with symptoms of hypogonadism particularly in male patients.
Serum prolactin is affected by many factors, for example stress, nipple stimulation, interfering medications and PCOS, and so should always be repeated on at least two occasions.
Elevated prolactin levels should also prompt the PEG precipitation test to determine whether this is biologically active or the inactive 'macroprolactin'.
Thyrotoxicosis commonly causes oligomenorrhoea or secondary amenorrhoea mimicking hopogonadism.
Thyroid dysfunction is more common in people with Turner’s syndrome. It is essential to assess levels of both thyroxine and TSH in patients suspected of pituitary disease.
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.
Estrogen replacement therapy leads to elevation of cortisol binding globulin and hence serum cortisol and so is difficult to interpret.
Ensure patients have stopped sex steroid therapy, for example HRT or the combined oral contraceptive pill for six weeks prior to test.
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.
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 pituitary should be performed in all patients with confirmed hypogonadotropic hypogonadism and should include the olfactory bulbs in patients with suspected Kallmann’s syndrome. Late onset, mild, isolated hypogonadism may not require imaging however.
A chest XR should be performed in all patients with multiple congenital abnormalities and with Turner’s syndrome.
This is usefully performed at presentation as it is required prior to starting dopamine agonist therapy or testing dynamic pituitary function if necessary.
This is performed to seek coarctation of the aorta in patients with confirmed Turner's syndrome at diagnosis and subsequently three to five yearly.
Ultrasound of the renal system is performed at diagnosis of Turner’s and Kallmann’s syndromes as anatomical abnormalities occur more frequently in people with these conditions.
This is useful to perform in most patients presenting with absent or delayed puberty to identify and locate the gonads, and to assess uterine size prior to considering pregnancy in female patients.
Consider performing plain radiograph to assess bone age in younger patients with delayed puberty.
This is performed every five years in people with Turner's syndrome.
Formal visual field testing is mandatory if there is clinical or MRI suspicion of chiasmal impingement in patients with pituitary disease.
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 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.
This should be considered in all patients with long standing hypogonadism. It may be useful to repeat after five years of treatment.
Low serum vitamin D levels strengthen the case for vitamin D replacement therapy in patients with osteoporosis of any cause.
Patients with the phenotypic features of pseudohypoparathyroidism should have PTH levels documented to determine their underlying diagnosis.
Levels will be low in hypoparathyroidism, high in pseudohypoparathyroidism, and normal in patients with pseudopseudohypoparathyrdoidism.
This should be performed at presentation in patients with absent puberty, and in all patients with suspected Turner’s, androgen insensitivity and Klinefelter’s syndrome.