concentrations cannot be measured with adequate
reliability, functional status is assessed by the
measurement of some other function marker, the
quantity of which is predictably related to the plasma
concentration of bioactive hormone. There may be
cosecreted products that are released from the
endocrine gland at rates proportional to the hormone
secretion rate. Catabolic products arising from
degradation of the hormone within the gland itself
and within peripheral tissues can be used. So can
effector metabolites, which are either intracellular
messengers, e.g., cyclic adenosine monophosphate,
or products of intermediary metabolism that are
released from effector tissue in proportion to the
degree of hormone binding. These function markers
may be quantified by measurement of their plasma
concentrations or by measurement of their renal
elimination rates. The hormone's physiologic effect
also may be evaluated, including its effect upon the
plasma concentration of its trophic hormone. In
diabetes mellitus, insulin secretory capacity is
estimated from the clearance rate of a glucose load,
insulin's physiologic effect. Insulin production by
an insulinoma, on the other hand, is monitored by
measurement of plasma C-protein, a cosecreted
product.
The measurement of an endocrine function
marker rarely permits complete separation of
patients according to functional status. More
typically, the function categories overlap, sometimes
extensively, when even the most reliable function
marker available is used. To separate the function
categories more completely, an endocrine gland can
be stimulated or suppressed. Stimulation of the
gland by administration of its trophic hormone or by
depressing the feedback signal is especially useful in
the separation of primary hypofunction from normal
function. When transiently stimulated, a normal
gland will, for a period of time, increase the rate of
secretion of hormone. A hypofunctional gland will
not respond to the stimulation with a comparable
increase in secretion rate. Figure 7.9 illustrates why
this is so. The control response curve for a
hypofunctional gland will be displaced from the
normal response curve and will be flattened because
the maximal secretory capacity of the gland is
reduced (top graph). Consequently, perturbation of
the hypofunctional system by an exogenous stimulus
(the time course of stimulation is presented in the
middle graph) will not result in changes in the
magnitude of the function marker equal to those seen
with a normally functioning gland (bottom graph).
The area between the function marker curve and the
basal level of the function marker is proportional to
the amount of hormone secreted in excess of the
basal output,
area between the curves =
amount of excess hormone secreted
clearance rate
The clearance rate for circulating hormone is usually
the same in the setting of endocrine hypofunction as
it is during normal function, so the index "area
between the curves" is a reliable marker of excess
hormone secretion during stimulation. A hypofunc-
tional gland will secrete less excess hormone and
therefore will have a measurably smaller "area
between the curves." In this way a hypofunctional
gland can be distinguished from a normally function-
ing one. In the figure, the "area between the
curves" for the normal gland is 3 times larger than
that for the hypofunctional gland even though the
basal function marker levels differ by less than 10
percent.
The suppression of endocrine gland hormone
secretion by alteration of the feedback signal can be
used to improve the diagnostic separation of primary
hyperfunction from normal function. During the
period of suppression, a normal gland will markedly
reduce its rate of hormone secretion. The reduction
in the secretion rate will be less is a hyperfunctional
gland. Figure 7.10 shows that the reason for this is
that hyperfunctional glands also have displaced and
flattened control response curves. In a suppression
study, the area between the function marker curve
and the basal level of the function marker is a
reliable marker of the hormone secretion deficit. A
hyperfunctional gland will not suppress its secretion
very much below its basal state so its secretion
deficit will be small compared to normal.
Rather than following the full time course of a
function marker during a stimulation or suppression
study, a single measurement taken at a specified
time, preferably at a time near the extreme point of
the function marker curve, can be used to quantify
the hormone secretion excess or deficit. The magni-
tude of the function marker at the specified time will
be linearly related to the amount of the excess or
deficit. Such a one-sample study technique intro-
duces measurement variability due to interindividual
differences in the time to peak function marker
change but clinical experience has shown that
Organ Function
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