Endocrine Function Tests
In general, patients with endocrine disorders present to clinicians because they are thought to have either hormone excess or hormone deficiency and each of these states has a variety of underlying causes. The accurate diagnosis of clinical endocrine disease depends upon knowledge of the principles of feedback control described in Chapter 7, on an understanding of basic endocrine biochemistry and on the availability of high quality assay systems provided by chemical pathology laboratories (Fig. 8a).
Many hormones are secreted in a pulsatile fashion, often subject to diurnal or ultradian rhythms, such that a single, untimed blood sample may be of little or no diagnostic value. There are important exceptions to this rule, in particular thyroid disease in which basal measurements of TSH and free thyroid hormone concentrations are diagnostic in the vast majority of cases, hyperprolactinaemia in which a single result in an unstressed patient is reliable and calcium and PTH measurements which are stable. Characteristically, endocrine disorders disrupt normal feedback mechanisms and this feature is exploited in the interpretation of a number of endocrine function tests. Furthermore, certain hormones rise in response to stressful stimuli and this too can be utilized for diagnostic purposes. Because of these special considerations, collection of anything other than basal and straightforward blood samples must be undertaken by experienced staff who are aware of the appropriate local protocols. In hospital endocrine referral centres, specialist nurses are skilled in correct patient preparation for the tests, the delivery of drugs required for hormone stimulation or suppression, careful clinical monitoring of patients, observation for side effects during the tests and correct management of samples. The latter forms a vital part of dynamic testing protocols and more complex investigations should always be performed in conjunction with chemical pathology staff to ensure that samples are collected into the correct pre- servatives at the necessary temperature and maintained in ideal conditions prior to transfer to the laboratory.
Careful recording of the timing of the test, any symptoms experienced by the patient and the results are essential.
There are many dynamic function tests employed in clinical endocrinology and clinicians must refer to local protocols and normal ranges. Examples of some commonly used dynamic endocrine function tests are shown in Fig. 8b. Two examples follow which illustrate some important principles of endocrine testing.
Insulin tolerance test
The insulin tolerance test (ITT) is used to assess the anterior pituitary reserve of growth hormone (GH) and adrenocorticotrophin (ACTH), both of which are stress hormones and rise in response to illness and hypoglycaemia. The ITT tests the response to a hypoglycaemic stimulus which acts at the level of the hypothalamus to stimulate the production of these pituitary counter-regulatory hormones. The ITT is contraindicated in patients with significant ischaemic heart disease, epilepsy, glycogen storage diseases and severe hypoadrenalism (0900 h cortisol <100 nmol/l). Thus a 0900 h cortisol measurement and ECG must be performed prior to the test and 25% dextrose and hydrocortisone available for intravenous injection during the test if required. An experienced nurse and a doctor must be present throughout and resuscitation equipment be available. If in doubt, a glucagon test should replace the ITT, although it produces less reliable results.
Patients fast from 2200 h the night before the test, which should start at 0900 h. After weighing, soluble insulin (Actrapid) is given as a bolus dose of 0.15 U/kg. Blood samples are taken for glucose, cortisol and GH at regular intervals – the blood glucose must fall below 2.2 mmol/l to provide an adequate hypoglycaemic stimulus (further insulin may be given if this is not achieved). At the end of the test the patient must be given food to eat and 100 mg iv hydrocortisone if the hypoglycaemia was severe. Fig. 8c shows a typical ITT recording chart. Results may vary from laboratory to laboratory and advice about normal responses should be checked locally. In general, severe GH deficiency is indicated by a peak GH of 3 µg/L or less and a normal peak cortisol should exceed 550 nmol/L.
Water deprivation test
A water deprivation test (WDT) is performed when there is a clinical suspicion of either central or nephrogenic diabetes insipidus (see Chapter 36) or to investigate thirst and polyuria. Like the ITT, extreme care is needed to perform a WDT and constant supervision to prevent the patient from drinking, to monitor body weight and to handle plasma and urine samples appropriately. Extreme caution should be taken in patients with severe DI and the diagnosis may be made on overnight basal samples alone where the plasma osmolality is >295 mosmol/kg and the urine osmolality/plasma osmolality ratio (U/P) is <2.0.
Before starting the WDT the patient should be allowed to drink freely to 0800 h but should avoid tea, coffee or smoking. The patient should be weighed and 97% of this weight recorded. From 0800 h all fluid intake is discontinued for 8 hours. The patient is weighed and urine and plasma samples taken hourly for measurement of urine volume and urine and plasma osmolalities. If the weight loss exceeds 3% of body weight the test is discontinued, plasma osmolality measured urgently and desmopressin given if osmolality >305 mosmol/kg. Assuming the test continues, at 1600 h desmopressin 2 µg is given intra- muscularly and urine and plasma samples continued for a further 4 h.
In cranial diabetes insipidus the plasma osmolality rises with inappropriately high urine volumes and no evidence of concentration. After desmopressin, urine volumes fall with normal concentration. In nephrogenic diabetes insipidus the urine fails to concentrate after desmopressin injection. Results in primary polydipsia are variable and urine concentration may not maximize due to previous high urine volumes causing a decrease in the osmotic gradient in the loop of Henle.