Dynamic function tests

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41

Dynamic function tests

Much of clinical endocrinology is concerned with diseases that involve either a deficiency or an excess of hormones. It is not always possible to diagnose these diseases on the basis of clinical assessment and baseline laboratory investigations. Dynamic function tests (DFTs) involve either stimulating or suppressing a particular hormonal axis, and observing the appropriate hormonal response. In general, if a deficiency is suspected, a stimulation test should be used; if excess is suspected, a suppression test is used. Often, the stimulus is an exogenous analogue of a trophic hormone; in other cases it is provided by biochemical or physiological stress, e.g. hypoglycaemia or exercise.

On subsequent pages, individual DFT procedures are discussed in the context of specific hormonal axes. Here, we describe the principles that underpin some of these DFTs, and look at aspects of interpretation. The abbreviations used for the various hormones and the tests are listed in Tables 41.1 and 41.2 respectively.

Table 41.1

Abbreviations for some hormones

Adrenocorticotrophic hormone ACTH
Arginine vasopressin AVP
Corticotrophin releasing hormone CRH
Follicle stimulating hormone FSH
Gonadotrophin releasing hormone GnRH
Growth hormone GH (or HGH)
Growth hormone releasing hormone GHRH
Luteinizing hormone LH
Parathyroid hormone PTH
Thyroid stimulating hormone TSH
Thyrotrophin releasing hormone TRH
Thyroxine T4
Triiodothyronine T3

Table 41.2

Commonly used abbreviations for various dynamic function tests

IST Insulin stress test
OGTT Oral glucose tolerance test
SST Short Synacthen test
DST Dexamethasone suppression test
CAPFT Combined anterior pituitary function test

Insulin stress test

This test is carried out when hypopituitarism is suspected. It is also known as the insulin tolerance test. Enough insulin is administered to produce hypoglycaemic stress (blood glucose <2.2 mmol/L). This tests the ability of the anterior pituitary to produce ACTH and GH in response. Cortisol is measured instead of ACTH; this assumes that the adrenals can respond normally to ACTH. A peak GH in excess of 6 µg/L is regarded as evidence of adequate reserve. For cortisol there is less consensus about what should be regarded as an adequate response; however, anything less than 500 nmol/L is inadequate, and many endocrinologists use cut-offs substantially in excess of this, e.g. 550 nmol/L. An example of the results of an insulin stress test is shown in Figure 41.1.

TRH test

TRH is given as an intravenous bolus; blood sampling is at 0, 20 and 60 minutes (Fig 41.2). In normal subjects TRH elicits a brisk release of both TSH and prolactin. This test may be used to assess the adequacy of anterior pituitary reserve, or to evaluate suspected hypothalamic disease, in which the TSH response to TRH is characteristically delayed (TSH higher at 60 minutes than at 20 minutes). Much less frequently it may be indicated in suspected hyper- or hypothyroidism or subclinical thyroid disease. Where there has been prolonged negative feedback due to hyperthyroidism, the pituitary response to TRH is flat (TSH rises by <2 mU/L); conversely, an exaggerated TSH response (>25 mU/L) is seen in hypothyroidism.

Synacthen tests

Short Synacthen test

The short Synacthen test (SST) is one of the most commonly performed DFTs. The procedure is described on page 97. Of the three criteria that are used to define a normal response (see Fig. 48.3 on p. 97), the final cortisol is the most important, and the increment the least important. As with the IST, there is lack of agreement on what constitutes an adequate cortisol response to Synacthen; cut-offs for the final level vary between 500 and 580 nmol/L.

Dexamethasone suppression tests

Dexamethasone is an exogenous steroid that mimics the negative feedback of endogenous glucocorticoids. Dexamethasone suppression tests (DSTs) are important in the investigation of suspected overactivity of the hypothalamic-pituitary-adrenal axis.

High dose dexamethasone suppression test

Failure to suppress in response to low dose dexamethasone may occur because of autonomous ACTH production by the pituitary (Cushing’s disease), or ectopic ACTH production (usually malignant), or adrenal production of cortisol (see p. 98). The high dose DST (8 mg) is used to distinguish the first two of these options. ACTH production in Cushing’s disease does usually suppress in response to high dose dexamethasone, whereas malignant production of ACTH usually does not.

Dynamic function tests – protocol variation

Protocols for individual DFTs vary from one centre to another. For example, an additional cortisol specimen is collected at 60 minutes in some SST protocols, although this rarely alters the interpretation of the SST. Likewise, the long Synacthen test may be performed as a day-long procedure, with 1 mg Synacthen administered in the morning and cortisol samples collected for up to 24 hours; others perform this test as outlined on p. 97. The reasons for the different protocols are often practical rather than evidence-based but it is always wise to check with the local laboratory before proceeding with any DFT.