Endocrine investigations Table 391

A baseline assessment of the endocrine status should include measurement of serum prolactin and gonadotropin concentrations and an assessment of thyroid function. Pro-lactin levels may be elevated in response to a number of conditions, including stress, a recent breast examination, or even having a venepuncture. The elevation, however, is moderate and transient. A more permanent, but still moderate elevation (greater than 700 mIU/1) is associated with hypothyroidism and is also a common finding in women with PCOS, where prolactin levels up to 2500 mlU/l have been reported [1]. PCOS may also result in amenorrhoea, which can therefore create diagnostic difficulties, and hence appropriate management, for those women with hyperprolactinaemia and polycystic ovaries. Amenorrhoea in women with PCOS is secondary to acyclical ovarian activity and continuous oestrogen production. A positive response to a progestogen challenge test (e.g. medroxyprogesterone acetate 10 mg daily for 5 days), which induces a withdrawal bleed will distinguish patients with PCOS related hyperprolactinaemia from those with polycystic ovaries and unrelated hyperprolacti-naemia, because the latter causes oestrogen deficiency and therefore failure to respond to the progestogen challenge.

A serum prolactin concentration of greater than 1500 mlU/l warrants further investigation. Computerized tomography (CT) or magnetic resonance imaging (MRI) of the pituitary fossa may be used to exclude a hypothalamic tumour, a non-functioning pituitary tumour compressing the hypothalamus or a prolactinoma. Serum prolactin concentrations greater than 5000 mlU/l are usually associated with a macroprolactinoma which by definition are greater than 1 cm in diameter.

The patient's oestrogen status maybe assessed clinically by examination of the lower genital tract, or by means of a progestogen challenge. Serum measurements of oestra-diol are unhelpful as they vary considerably, even in a patient with amenorrhoea. If the patient is well oestroge-nized the endometrium will be shed on withdrawal of the progestogen.

Serum gonadotropin measurements help to distinguish between cases of hypothalamic or pituitary failure and gonadal failure. Elevated gonaotrophin concentrations indicate a failure of negative feedback as a result of primary ovarian failure. A serum follicle stimulating hormone (FSH) concentration of greater than 15 IU/L that is not associated with a preovulatory surge suggests impending ovarian failure. FSH levels of greater than 40 IU/L are suggestive of irreversible ovarian failure. The exact values vary according to individual assays, and so local reference levels should be checked [2]. It is important also to assess serum gonadotropin levels at baseline, that is during the first 3 days of a menstrual period. In patients with oligo/amenorrhoea it may be necessary to perform two or more random measurements, although combining assessment of endocrinology with an ultrasound scan on the same day aids the diagnosis.

An elevated luteinizing hormone (LH) concentration, when associated with a raised FSH concentration, is indicative of ovarian failure. However, if LH is elevated alone (and is not attributable to the preovulatory LH surge), this suggests PCOS. This may be confirmed by a pelvic ultrasound scan. Rarely an elevated LH in a phenotypic female may be due to androgen insensitiv-ity syndrome (AIS), although this condition presents with primary amenorrhoea.

Failure at the level of the hypothalamus or pituitary is reflected by abnormally low levels of serum gonadotropin concentrations, and gives rise to hypogo-nadotrophic hypogonadism. Kallman's syndrome is the clinical finding of hyposmia and/or colour blindness associated with hypogonadotrophic hypogonadism - usually a cause of primary amenorrhoea. It is difficult to distinguish between hypothalamic and pituitary aetiology as both respond to stimulation with gonadotropin releasing hormone (GnRH). A skull X-ray should be performed and CT or MRI if indicated.

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