Adrenal Gland: I Adrenal Medulla
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).
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.