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Endocrine system 11

Clinical, 420 Growth axis, 425 Disorders of the parathyroids, 446
The hypothalamus and pituitary, Thyroid axis, 427 Multiple endocrine neoplasia, 450
421 Adrenal axis, 436 Diabetes mellitus, 450
Dopamine and prolactin axis, 423 Thirst axis, 444

Hormones may act on glands to cause the secretion
Clinical
of other hormones and may also act to downregulate
their own production (negative feedback), for example
Principles of endocrine testing the action of thyroid hormones on the anterior pituitary
(see Fig. 11.1).
The endocrine system is the mechanism by which in-
Endocrine dysfunction generally results in over or un-
formation is communicated around the body using
der functioning of a gland. Reduced function may result
chemical messengers (hormones). These messengers are
from a number of mechanisms. For example, hypothy-
secreted by glands and may be transported through the
roidismmayresultfromafailureoftheanteriorpituitary
bloodstream to a distant target organ (endocrine ac-
gland or a failure of the thyroid gland. Endocrine test-
tivity) or may act directly on local tissue (paracrine
ing is used to both identify the lack of hormone and to
activity). Hormones are of various types including pep-
elucidate the underlying cause. For example,
tides, glycoproteins, steroids or amines such as cate-
measurement of thyroid hormones is used to detect
cholamines.
hypothyroidism
Peptide, glycoprotein and amine hormones act by

measurement of thyroid stimulating hormone (TSH)
binding to cell surface receptors, which initiate a cas-
helps to identify the cause. A low TSH signifies failure
cade of intracellular signalling molecules. These hor-
of the anterior pituitary (secondary hypothyroidism).
mones may be synthesised and stored as inactive pre-
A high TSH signifies failure of the thyroid gland (pri-
cursors (prohormones).
mary hypothyroidism).
Steroid hormones and thyroid hormones circulate

Clinical features of apparent hormone deficiency may
freely and bound to plasma proteins. It is only the
also result from a failure of response at the target organs.
unbound (free) hormone that is biologically active.
Some hormones have cyclical or pulsatile secretion.
The bound hormone acts as a buffer against rapid
In these cases a single random hormone sample will not
changes in hormone levels. Steroid hormones act via
determine whether the level is high or low. In such ins-
intracellular receptors, which travel to the cell nucleus
tances either testing at specific times of day (e.g. early
and regulate DNA transcription and hence protein
morning cortisol levels) or dynamic endocrine testing is
synthesis.
required. Dynamic endocrine testing uses techniques to
The sensitivity of target organs to a hormone is depen-
stimulate or suppress hormone secretion. For example,
dent on the level of receptor expression. Prolonged ex-
cortisol is secreted from the adrenal glands in response
posure to a hormone often results in receptor downreg-
to adrenocorticotrophin hormone (ACTH). Adminis-
ulation, whereas absent or minimal hormone exposure
teringasyntheticACTH(Synacthen)allowstheresponse
leads to receptor upregulation.
of the adrenal glands to be assessed.
420