Adrenal Gland: I Adrenal Medulla
Clinical scenario
A 32-year-old accountant, Mr PT, went
to the Occupational Health Department at his workplace as he had been
experienc- ing headaches and palpitations for the last few months. These had
become increasingly frequent and his colleagues had noticed that he became
extremely pale at the times he com- plained of palpitations. At the time of
these episodes he had a bizarre sensation of extreme anxiety and fear of death.
There was nothing to find on examination apart from an elevated blood pressure
of 180/105. There was no significant family history.
The occupational health physician was
sufficiently concerned to refer him to the local Endocrine Department.
Investigations there revealed elevated levels of plasma and urine
metanephrines. Abdominal MRI scans and radioisotope scanning using
iodine-labelled meta-iodobenzyl guanidine (MIBG) demonstrated a 5 × 6 cm mass
in the region of the right adrenal gland consistent with a phaeochromocytoma.
He was treated with the α-adrenoceptor-blocking drug phenoxybenzamine with the
later addition of the β-blocker pro- pranolol prior to surgery 6 weeks later.
At operation the phaeochromocytoma was removed and he made an uneventful
recovery.
Phaeochromocytomas are rare tumours of
the adrenal medulla secreting catecholamines, usually norepinephrine The
majority are sporadic, benign lesions although approximately 10% are familial
and 10% malignant. In approximately 10% of cases they are extramedullary,
making localization difficult. Phaeochromocytomas may be part of the Multiple
Endocrine Neoplasia Type 2 syndrome (MEN 2; Chapter 50).
The adrenal glands
The adrenal glands lie just above the
kidneys (Fig. 16a), and can be divided on anatomical and functional grounds into
two main suborgans: (1) the
adrenal cortex, which
secretes the steroid hormones;
and (2) the adrenal medulla, a modified ganglion, which secretes the
catecholamines epinephrine (EP) and norepinephrine (NE).
Adrenal medulla
Catecholamine synthesis (Fig. 16b). The adrenal medullary chromaffin cells
can be distinguished as EP-storing and NE- storing cells.
EP and NE are stored in granules,
together with a protein, chromogranin, and adenosine triphosphate (ATP). When
exo- cytosed, the granule releases all its contents.
Metabolism (Fig. 16c). Catecholamines are metabolized
extracellularly and in the liver by catecholamine-O-methyl-transferase
(COMT), and intracellularly by monoamine oxidase (MAO). MAO is localized close
to the adrenoceptors where EP and NE act. Catecholamine action is not
terminated by enzymes, however, but through reuptake into the cell from which
they were released. VMA is excreted in the urine. In sympathetic nerves, NE
feeds back onto presynaptic α-2 receptors, which limit further release of NE.
Metabolites are measured in urine and are diagnostic in phaeochromocytoma.
Actions of epinephrine
Epinephrine has been called the
hormone of ‘flight or fight’. Stressors cause an immediate release of EP, which
prepares the body for extraordinary physical and mental exertion (Table 16.1).
Surface vasculature shuts down by the constriction of arteriolar tissue through
the mediation of α-1 receptors, thus limiting potential blood loss through
injury; in contrast, the vasculature to the muscular beds opens up through the activation
of the β-2 receptors. Dilation of bronchioles increases the efficiency of
oxygen intake in unit time, and glucose mobiliza- tion is enhanced through the
stimulation of glucagon release and the inhibition of insulin release.
Dilation of the radial muscles of the iris in the eye increases the
availability of light to the retina, and the contraction of the splenic capsule
releases blood cells into the circulation. Through β-1 receptors in the heart,
contractility is greatly increased. Epinephrine promotes lipolysis and
thermogenesis through β-3 receptors. EP also increases mental alertness,
although the exact mechanism is unknown.
Mechanism of epinephrine action (Fig. 16d). An example of EP action is the
mobilization of energy in the form of glucose. EP also acts on β receptors in
muscle to inhibit release of amino acids, thus reducing the rate of muscle
proteolysis. This mechanism may be important in the fight or flight response, when
muscle would be spared from providing energy. Although little NE is released
from the adrenal medulla, it is the major neurotransmitter of the sympathetic
nervous system which is activated during fight or flight.
