SYMPTOMS OF ENDOCRINE DISEASE

Symptoms of
endocrine disease

Hyperfunction
Causes: hyperfunction generally results from over-secretion of
a hormone from a tumour that becomes autonomous, or as a
result of failure of suppression of production of the hormone.
The immune system can cause hyperfunction when antibody
binds to and stimulates the thyroid-stimulating hormone receptor
(Graves disease).

Karim Meeran

Clinical features: symptoms of hyperfunction are organ

specific and are discussed in the relevant contributions to the
Endocrine Disorders chapter of MEDICINE.

Hormone concentrations can vary widely in an attempt to regulate

for changes in the environment. Their levels are often regulated by
negative feedback, which usually results in tight control of a system.
One difficulty in diagnosing endocrine disease is that hormone
levels may be in the published reference range, even in patients
with significant disease. This is because the concentration of hormones should vary depending on other, extraneous factors, and
the normal range does not take account of this. Thus, hyperfunction can be missed because the measured levels remain within the
reference range. In primary hyperparathyroidism, for example, the
concentration of parathyroid hormone may be within the reference
range despite high calcium levels, though it should be suppressed;
the fact that it is not confirms primary hyperparathyroidism. In
Cushings disease, cortisol and adrenocorticotrophic hormone may
both be within the reference range.
Diagnosis in endocrine disorders therefore relies on dynamic
tests, usually performed at a defined time of day. Although a
random growth hormone (GH) level is usually unhelpful in the
diagnosis of acromegaly, GH measured during an oral glucose
tolerance test is likely to be helpful.
Problems occur when the regulation of hormone production
fails. This can result in hyperfunction (Figure 1) or hypofunction
(Figure 2).

Investigations: a suppression test is more likely to demonstrate

hyperfunction than a static test. The only indication of
hyperfunction might be non-suppressibility of the hormone
concerned, and if this is suspected, referral to an endocrine unit
is essential.
It is generally not possible to interpret hormone measurements
outside defined parameters. Endocrinologists are often asked
whether a patient in the ICU may have an endocrine disorder such
as Cushings disease or phaeochromocytoma, but it is usually
impossible to make such a diagnosis while the individual is an
in-patient.

Hypofunction
Causes: hypofunction commonly results from autoimmune
damage to the endocrine organ (as in primary hypothyroidism,
gonadal failure and Addisons disease). In the case of the
pituitary, which is enclosed in a bony case, the pressure caused
by a tumour can cause the cells to fail. Hypofunction can also be
iatrogenic, when an endocrine organ is removed or destroyed,
or as the result of drug treatment that suppresses hormone
production.
Clinical features: the onset of hypofunction is usually gradual
and patients often fail to notice any change. Lethargy, tiredness
and depression are common consequences of endocrine
hypofunction, and the diagnosis is often missed, particularly
because of the rarity of endocrine causes compared with other
causes of such symptoms.
Investigations: dynamic tests are useful in patients with
endocrine failure, and stimulation tests are essential. Serum
cortisol may be within the reference range in patients with
pituitary failure caused by pituitary adenoma, but may not
increase adequately under stress. During times of metabolic
stress, an adequate cortisol response is essential for normal
functioning.

Karim Meeran is Senior Lecturer and Consultant Endocrinologist at

Charing Cross and Hammersmith Hospitals, London, UK.

MEDICINE 33:11

2005 The Medicine Publishing Company Ltd