Kallmann's syndrome and hypogonadotropic hypogonadism

The diagnosis of Kallmann's syndrome comprises hypogonadotropic hypogonadism associated with anosmia.

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. This should also be tested prior to testosterone treatment.


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

Liver function test may be surprisingly normal in cirrhosis.

Liver function should also be documented before starting testosterone replacement therapy in all patients.

Bone profile

Useful indicator of general health and underlying disease.

Hypercalcaemia may occur with glucocorticoid deficiency.

Prostate specific antigen

PSA should be documented before considering testosterone replacement therapy.

Baseline pituitary function

Estrodial/testosterone, sex hormone binding globulin

Due to the circadian release, sex hormones should be assessed early in the morning (typically at 9am), on more than one occasion and, in menstruating women, during the early follicular phase. They also need to be tested 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.

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 primary or auto-immune ovarian failure, or secondary to mumps or testicular trauma in males.


Hyperprolactinaemia frequently presents with symptoms of hypogonadism.

Serum prolactin is affected by many factors, for example stress, nipple stimulation, interfering medications and polycystic ovarian syndrome, 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'.

Thyroid stimulating hormone, free thyroxine

It is essential to assess levels of both thyroxine and TSH in patients suspected of pituitary disease, or with abnormalities of sexual development.

Congenital hypothyroidism is a recognised cause of pubertal delay. Thyrotoxicosis at any age, commonly causes oligomenorrhoea or secondary amenorrhoea mimicking hypogonadism. Thyroid dysfunction is also more common in people with Turner’s syndrome.

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 pituitary disease and levels below this may require formal assessment for ACTH reserve, for example with an insulin stress test or glucagon test.

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.

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 pituitary pathology should have a CXR performed as an assessment of general health and a simple screen for underlying malignancy.

This is also worthwhile in patients with multiple congenital abnormalities or with Turner’s syndrome.

Renal ultrasound scan

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.

Pelvic ultrasound scan

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.

Bone age

Consider performing plain radiograph to assess bone age in younger patients with delayed puberty.

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 rather than isolated hypogonadotropic hypogonadism.


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.

Insulin stress test

Insulin stress 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 test is contraindicated or unavailable, the arginine-GHRH test is a suitable alternative test of H reserve.

Bone densitometry scan

This should be considered in all patients presenting with 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.

Parathyroid hormone

Patients with phenotypic features suggestive of pseudohypoparathyroidism should have PTH levels documented.

Levels will be high in pseudohypoparathyroidism and normal in patients with pseudopseudohypoparathyrdoidism.