Adrenal glands

Surgical anatomy

At birth, the adrenal glands have attained nearly adult proportions. Fully developed, each weighs about 4 g, but the left is a little larger than the right. A deeper yellow colour and a firmer consistency enable the gland to be distinguished from the adjacent fat. Each rests on the superior, anterior and medial aspects of the superior pole of the corresponding kidney, and presents the appearance of a French Liberty cap worn at a rakish angle.

Although intimately related anatomically; the adrenal cortex and the adrenal medulla are quite separate internal secretory glands.

The adrenal glands are supplied by several adrenal arteries, rendering them remarkably vascular, but only one vein drains each gland. On the right side the adrenal vein is short and enters the inferior vena cava, while on the left it empties into the left renal vein [which communicates through the azygos vein with the left intercostal, internal mammary and vertebral veins (Anson)]. This dissimilarity of the right and left venous flow determines, to some extent, the location of metastases from malignant tumours of these glands.

  Diagnostic investigations

Computerised tomography (CT) has been a significant advance in imaging the adrenal glands and in the detection of adrenal masses with an accuracy of 90 per cent (Fig. 45.7). Ultrasonography can detect most adrenal masses larger than 2 cm in diameter, but is operator and machine dependent and less accurate, especially in obese patients. CT has made invasive techniques, such as selective retrograde venography and selective arteriography, almost obsolete. In those cases where CT findings are inconclusive and functional information is required, isotope scanning (see below) and differential venous sampling for hormone levels may be indicated.

A radiograph or CT scan of the pituitary fossa showing an enlarged pituitary fossa is suggestive of a basophil adenomas of the pituitary gland with excess adrenocorticotrophic hormone (ACTH) pituitary secretion.

Adrenal gland scintigraphy using NP-59 [1311-6(-iodomethyl-19Norchest-5(10)EN-3beta-ol] is of value in addition to CT. In a benign functioning adrenal tumour there is uptake with suppression of the contra lateral gland. By contrast adrenocortical carcinoma does not usually concentrate the isotope and, as a result of contra lateral gland suppression, there is little uptake. Bilateral adrenal hyperplasia produces the opposite result with a prominent bilateral image.

MRI is of value particularly for small lesions.

Adrenal cortex

The adrenal cortex is made up (if the following layers from without inwards: the zona glomerulosa, the zona fasciculata and the zona reticularis.

Physiology. At least 50 steroid compounds have been isolated from the adrenal cortex. These hormones exhibit various types tif activity which, for practical purposes, can be arranged in three groups.

Mineralocorticoids are concerned in the maintenance of water and electrolytic balance. A deficiency of these hormones produces sodium diuresis, potassium retention and dehydration; an excess results in hypertension, oedema, cardiac dilatation and hypokalaemia. Aldosterone is the most important of these  salt-regulating’ hormones (see Conn’s syndrome later).

Glucocorticoids are concerned with the metabolism of proteins and carbohydrates, favouring the formation of the latter from the body’s storehouse of the former. This conversion is known as gluconeogenesis. The best known of these are hydrocortisone (also known as cortisol) and cortisone (which is converted in the body to hydrocortisone). The therapeutic application of these hormones falls under two headings.

In endocrine deficiencies. Hydrocortisone is the logical need in adrenocortical insufficiency and after bilateral adrenalectomy.

In nonendocrine disease. Hydrocortisone or synthetic analogues, such as prednisone and betamethasone, are used in the treatment of a diversity of diseases, including allergic conditions, granulomatous disorders, blood diseases and the collagenoses. Hydrocortisone is used in the treatment of hypocorticism and shock (Chapter 4) and is an effective antiallergic agent in a number of skin diseases and eye conditions.

Sex hormones. Androgenic and oestrogenic hormones are produced by the adrenal cortex. Excessive secretion of androgens due to adrenal enzyme deficiencies or tumours causes virilism in females or, rarely, excessive secretion of oestrogens brings about effeminacy in males.

Interhormonic action. The anterior lobe of the pituitary gland secretes ACTH which stimulates the adrenal cortex, whereas the cortisol of the adrenal cortex inhibits the secretion of ACTH. ACTH secretion is also controlled by higher cerebral centers and the hypothalamic corticotrophin-releasing hormone (CRH).

Tests of adrenocortical activity

The tests are of two types, those that confirm the presence of a change in cortisol production and those that indicate a cause. No tests should be interpreted in isolation but all the results of the investigations should be considered together.

Plasma electrolytes. Sodium levels are raised and potassium is low in a hyper functioning adrenocortical lesion with the opposite in Addison’s disease, but changes in Addison’s disease may not occur until the patient is approaching crisis.

Plasma cortisol levels. Diurnal variation with a maximum value at 8.00 am. may be lost both in Cushing’s syndrome, where all levels are high, and in insufficiency when levels are low.

Plasma ACTH levels. Low plasma levels are found with adrenal tumours and high levels with a pituitary lesion or ectopic ACTH production. The ratio of ACTH to related peptides such as beta-lipotrophin may facilitate the distinction between pituitary Cushing’s and ectopic ACTH production.

Plasma aldosterone levels. The concentration of aldosterone is only one-thousandth that of cortisol, and both dietary sodium and posture may change the value. Plasma renin levels should be measured along with aldosterone to differentiate between primary and secondary hyperaldosteronism.

Urinary steroid excretion. Cortisol secretion rate. The daily output of cortisol is a precise measure of adrenocortical activity, but is routinely performed in only a few centres. Adult levels are reached by 18 years of age and after 40 years fall gradually, to be halved by 70 years of age. The average excretion is higher in Caucasian males. The daily output may be determined by the administration of a small amount of radioactive-labelled cortisol, which is metabolised and excreted, and the urinary radioactivity measured. The normal range is 5—28 mg per 24 hours, with high levels in Cushing’s syndrome and low levels in adrenal insufficiency.

Urinary cortisol excretion. The cortisol excretion in a 24-hour urine sample is probably the best screening test for adrenocortical over secretion.

I 7-Oxosteroids or ketosteroids. These reflect androgen output, and excretion is increased in many women with virilising syndromes.

Dexamethasone suppression test. Dexamethasone is 25 times more potent than cortisol. Dexamethasone 0.5 mg is administered 6-hourly for 2 days and causes a marked decrease in urinary steroid excretion by inhibiting ACTH production, and thus cortisol, without contributing greatly to the total urinary steroid output. In Cushing’s syndrome, no effect is produced by the dose. Larger doses of up to 2 mg 6-hourly will, over several days, reduce urinary steroid excretion if the overactivity is secondary to bilateral adrenal hyperplasia, but not with an adrenal tumour, which is autonomous. Measurement of the plasma cortisol at 9.00 a.m. after the administration of 2 mg dexamethasone the previous midnight serves as a convenient screening test for Cushing’s syndrome.

Metyrapone test. This differentiates between excess ACTH produc­tion and a lesion in the adrenal cortex causing Cushing’s syndrome. Metyrapone inhibits the biosynthesis of cortisol so plasma levels fall. If the pituitary—adrenal axis is intact, this results in an increase in ACTH production and stimulation of the adrenal cortex. The basal levels of 17-oxosteroids and ketosteroids in the urine are measured for 2 days, 750 mg of metyrapone is given per 4 hours and a 24-hour urine collection completed. A normal response is a two to fourfold increase in the urinary steroids over basal levels. A diminished response in Cushing’s syndrome indicates a primary adrenal lesion.

Synacthen test. Tetracosactrin (Synacthen) 250 pg is given intra­muscularly and blood cortisol measured at 30 and 60 minutes. In normal subjects the basal plasma cortisol should be greater than 60 pg/litre and be at least 70 pg/litre after stimulation. In Addison’s disease the response is impaired.

Disorders of adrenocortical function

Acute hypocorticism. Adrenal apoplexy in the newborn. Extensive haemorrhage into one or both adrenals may be a cause of death in infants within the first few days of birth. The condition may occur after a long and difficult labour, and particularly when resuscitative procedures have to be employed to combat asphyxia neonatorum. The haemorrhage into the adrenals follows necrosis of the innermost layer of the cortex, which always occurs at birth, possibly as a result of sudden withdrawal of the female sex hormone (oestrogen). Adrenal crisis in the newborn produces signs of profound shock. A mass may be palpable in one or hoth renal regions. Intravenous fluid therapy with hydrocortisone, or failing the latter, cortisone intramuscularly, offers the only hope.

Waterhouse—Friderichsen syndrome. Massive bilateral adrenal cortical haemorrhage occurs in eases of fulminating meningococcal septicaemia and in some cases of streptococcal, staphylococcal or pneumococcal septicaemia. Most cases occur in infants and young children, but it can happen in adults with severe haemorrhage or burns. The onset is catastrophic, with rigors, hyperpyrexia, cyanosis and vomiting. Petechial haemorrhages into the skin which coalesce rapidly into purpuric blotches are a constant feature. Profound shock follows, and before long the patient passes into coma. The condition is one of overwhelming sepsis that pursues a galloping course, death occurring in most eases within 48 hours of the onset of symptoms unless correct treatment is given without delay.

Unilateral haemorrhage causing a lesser degree of systemic upset and not associated with infections has been described. This type of case resembles a perinephric abscess or other upper abdominal acute condition.

Confirming the diagnosis. It is futile to await the result of a blood culture. Bilateral tenderness 5 cm below the costal margin, clear urine (oliguria is often present) and an absence of signs in the lungs help to call attention to the adrenal glands. In meningoccocal infection the diplococcus may be demonstrated by smears obtained from a punctured petechial spot in the skin.

Treatment. Antibiotic therapy must be given intensively by the intravenous route. Hydrocortisone 100 mg is given intravenously (i.v.), or intramuscularly (i.m.) if venous access is difficult. Up to 400 mg hydrocortisone may be required in the first 24 hours. No mineralocorticoid is needed as the weak intrinsic salt-retaining action of hydro­cortisone suffices at this dosage. Oral medication may be commenced after the first day and then over about 4 days reduced to a maintenance level. Oxygen should also be administered. Following such treatment, improvement often sets in within 3 hours, and a number of patients has recovered.

Crises of infantile hypercortism. See later.

Following bilateral adrenalectomy. If precautions are taken, acute hypocorticism is unusual in the postoperative period. Treatment is to give 300 mg hydrocortisone on the first day. Most patients achieve a maintenance dose of 30 mg/day. After about 3 weeks fludrocortisone 0.1 mg may be given.

Postoperative adrenal haemorrhage. Adrenal haemorrhage is a rare unexpected cause of deterioration and sudden death in the postoperative period. In some cases the left adrenal gland is damaged during radical gastrectomy for carcinoma (Fox). In other cases, when adrenal haemorrhage is bilateral, there is no evidence of operative injury, they are usually associated with intra-abdominal sepsis, pneumonia, coagulation defects and cancer. Thrombosis of the adrenal veins is the cause of infarction of glands.

Chronic hypocorticism (Addison’s disease)

This is due to adrenocortical insufficiency consequent upon progressive destruction with lymphocytic infiltration of the zona reticularis, the zona fasciculata, the zona glomerulosa and the medulla of the adrenal glands, in that order. In about 60 per cent of cases the condition is believed to be due to an autoimmune disease, sometimes in association with autoimmune thyroiditis (Chapter 44) and pernicious anaemia. Tuberculosis, meta­static carcinoma and amyloidosis account for the remaining 40 per cent.

Clinical features

Addison’s disease usually commences in the third or fourth decade. Sometimes it is the terminal event in cases of adrenogenital hyperplasia. The sex distribution is about equal. The leading features are muscular weakness and a low blood pressure. Irregular dusky pigmentation of the skin, due to deposits of melanin, appears at points of pressure, e.g. garter or belt, and in the flexion creases. Pigmentation of mucous membranes, particularly of the mouth, is often striking. When fully established, the course of the disease is punctuated by crises of acute adrenocortical insufficiency (see above).

Treatment

Treatment is medical. In long-term management, most patients require 20—3 0 mg hydrocortisone in divided doses, with fludrocortisone 0.1 mg daily as mineralocorticoid replacement. Signs of overtreatment include hypertension, hypokalaemia and oedema; those of under treatment, fatigue and hypotension. Where relevant, chemotherapy is manda­tory for tuberculosis (Chapter 8).

Prognosis

By the use of replacement corticosteroids, the expectation of life of a patient suffering from Addison’s disease has been extended from up to 3 years to many years.

Hypercorticism

The various forms of adrenal cortical hyperfunction are classified according to the age at onset:

 

infantile;

  prepubertal;

adult, otherwise known as Cushing’s syndrome — the commonest type;

 postmenopausal;

primary aldosteronism (Conn’s syndrome) can occur at any age.

 Infantile hypercorticism

Androgenic excess during intrauterine life is one form of pseudo­hermaphroditism in the female child. The condition is present at birth; sometimes the enlarged clitoris and a varying degree of hypospadias make it difficult to determine the infant’s sex. The 17-ketosteroid content of the urine may be sufficiently elevated to substantiate a diagnosis of a female with adrenal hyper function. If this is not the case, it is justifiable to perform sex determination by a skin biopsy before the age of 1 year. Female pseudohermaphroditism with virilism is invariably associated with disease of the adrenal cortex, usually bilateral hyperplasia of the cortex. Hormonal studies have shown that there is a congenital failure of the adrenal glands to synthesise glcocorticoids. Owing to this lack, these infants are liable to acute phases of adrenal insufficiency during stress or infection, or to suffer from periodic hypoglycemic attacks. They need corticosteroid replacement, not only in the emergency, but as long-term therapy, thereby inhibiting the secretion of excessive androgens. In the absence of such treatment, the epiphyses join early, the patients are dwarfed, menstruation does not occur and the breasts do not develop. These tendencies are corrected by hydrocortisone given orally, 25 mg or more daily, the dose being determined by 17-ketosteroid estimations (Simpson). Hirsutism is moderated, but not necessarily abolished. The treatment should be commenced early if good results are to be obtained.

Prepubertal hypercorticism

There is never any doubt as to the sex of the infant at birth and during the very early years of life the child is normal. The symptoms commence at about the age of 5 or 6 years.

In the female. Pubic and axillary hair appear, but there is no gross enlargement of the clitoris. The child is short in stature, the legs being especially stunted, but she looks much older than she is. Puberty is often precocious, menstruation, if it occurs, being scanty. There is a deepening of the voice at this time.

In the male. The term ‘infant Hercules’ is descriptive. He is extremely short, muscular and hirsute. The genitalia assume adult proportions and spermatozoa are often present in the seminal fluid.

In both sexes, 17-ketosteroid content of the urine is increased. A very high reading supports the diagnosis of an adrenocortical tumour, which must always be excluded. In both males and females, with a later onset or the passage of time, the features of Cushing’s syndrome become superadded.

Treatment. This is identical to that of Cushing’s syndrome.

Postpubertal or adult hypercorticism (Cushing’s syndrome)

Postpubertal or adult hypercorticism (Cushing’s syndrome) is due to an excessive endogenous production of glucocor­ticoids, mainly hydrocortisone. It is an uncommon condition, often suspected but seldom confirmed. Pituitary-dependent Cushing’s syndrome is the commonest form of endogenous hypercorticism accounting for up to two-thirds of all cases. An adrenal adenoma accounts for 20 per cent and carcinoma (which may be bilateral) 5 per cent. In the remainder there is no discernible structural alteration in the glands and the condition is due to an ectopic source of an ACTH-like substance being secreted, by either a benign tumour (e.g. bronchial carcinoid) or a malignant tumour of bronchus, mediastinum or pancreas. NonACTH-dependent primary adrenocortical hyperplasia is a rare cause of Cushing’s syndrome. Alcoholism also must be considered.

In its most typical form, Cushing’s syndrome is exogenous and is seen in patients treated with large doses of cortisone over long periods for nonendocrine diseases, particularly rheumatoid arthritis, and in patients receiving transplants.

Clinical features. The female to male ratio is at least 3:1. The great majority of cases (excluding those induced by cortisone therapy) occurs in females between 15 and 30 years of age, in whom it produces highly characteristic features. Although the patient’s weight is not necessarily increased, there is a deposition of fat in certain situations. The face becomes rubicund, rounded like a full moon, and the lips are pursed. The abdomen becomes protuberant, the neck thick, the supraclavicular fossae obliterated and a roll of fat appears over the region of the vertebra prominens (buffalo hump). The arms, and especially the legs, are relatively thin, the muscular development is poor, and the patient complains of increasing weakness. As the disease progresses, so the general contour becomes more and more that of a ‘lemon on match-sticks’ (Fig. 45.8). Consequent upon the inhibitory effect of the hypercorticism on fibrous tissue, the skin becomes of tissue-paper consistency and inelastic. Exceedingly  characteristic are purple-red striae distentiae, mostly on the abdomen (Fig. 45.9), of a texture that can be likened to an overstretched garter. Ecchymoses are frequent and bruising occurs on the slightest trauma. Acne is common and there is a low resistance to skin infections. Often there is increased growth of lanugo hair, but hirsutism is usually absent. Amenorrhoea is usual or, in the male, impotence. Owing to a negative calcium balance, the matrix of bone becomes thin and severe osteoporosis results. Pathological fractures, particularly compression fracture of a vertebra, are common, and this is sometimes the first reason for the patient seeking advice. Mild glycosuria is often present. Hypertension is frequent and eventually congestive heart failure supervenes. In about 60 per cent of cases, various psychoses occur.

Cushing’s syndrome is rare in children; when it occurs, the patient is nearly always a female and an adrenal tumour is usually the cause.

A subgroup, probably due to an excessive secretion of adrenal androgens (adrenogenital syndrome), commences between the ages of 15 and 25 and is confined to females. One of the first indications of its onset is amenorrhoea or oligomenorrhoea. There follows an excessive growth of hair on the face (Fig. 45.10), acne, atrophy of the breasts, alteration in bodily contour and muscular development, deepening of the voice and enlargement of the clitoris. Jewish and Spanish women are more prone to this affliction than those of other races.

Arrhenoblastoma of the ovary

This rare condition occurs between puberty and the menopause and also causes hirsutism. It may also arise in a suprarenal ‘rest’.

Screening tests. There are three simple tests (see above) which may be used to screen patients suspected to have Cushing’s syndrome:

  plasma cortisol levels and diurnal rhythm;

24-hour urinary free cortisol excretion;

overnight dexamethasone suppression test.

  Each of these tests is highly discriminating with false-positive and false-negative results in only about 5 per cent of cases. However, patients with severe or chronic illness or alcoholism may have elevated midnight plasma cortisol levels and may fail to show overnight suppression after dexamethasone.

Definitive diagnosis. Suspected Cushing’s syndrome may be confirmed by the low-dose dexamethasone suppression test (see above), which is highly reliable.

Differential diagnosis. After the diagnosis of Cushing’s syndrome has been established, it is necessary to determine the cause of adrenocortical hyperfunction. In general, adrenal hyperfunctioning tumours and ectopic ACTH-secreting tumours function autonomously and are unaffected by   hormonal manipulation. In contrast, the feedback mechanism in pituitary Cushing’s is functioning although it is abnormal. Thus appropriate investigations (see above) are the high-dose dexamethasone suppression test, measurement of plasma ACTH levels and the metyrapone test, which has largely been replaced by plasma ACTH assay. Nearly all patients with adrenal tumours and with the ectopic ACTH syndrome, in contrast to pituitary Cushing’s, fail to suppress with a high dose of dexamethasone and suppression is indicative of Cushing’s disease. In addition, patients with Cushing’s disease or the ectopic ACTH syndrome have detectable or elevated plasma ACTH levels, whereas cortisol-producing adrenal tumours suppress pituitary ACTH secretion and plasma levels are extremely low A high plasma ACTH level after high-dose dexamethasone indicates autonomous ACTH secretion by  a nonpituitary tumour, whereas if the ACTH level is low it indicates the presence of an adrenocortical tumour that has suppressed ACTH secretion by the normal pituitary.

Localisation studies. CT accurately identifies virtually all adrenal tumours in patients with Cushing’s syndrome and has replaced other techniques. It is also the most reliable method of detecting nodules in the lungs, mediastinum and pancreas, which are potential sites of ectopic ACTH production. Pituitary CT has also replaced other techniques for the detection of pituitary microadenomas in Cushing’s disease, although only 50 per cent of such adenomas are identified. Bilateral selective inferior petrosal venous sampling for ACTH levels is a valuable but technically difficult method of confirming and localising pituitary-dependent Cushing’s disease if CT is unhelpful.

Treatment. Trans-sphenoidal pituitary adenectomy in skilled hands is now the treatment of choice for pituitary lesions. External pituitary irradiation is less reliable in terms of long-term remission but is more successful in children. Yttrium-90 implantation is an alternative form of pituitary irradiation. Bilateral total adrenalectomy is a reliable procedure for patients with Cushing’s disease in whom pituitary treatment has failed.

The treatment of an adrenal tumour is surgical resection and resection of benign ectopic ACTH-secreting tumour is curative. Many, however, are malignant and widely disseminated when Cushing’s syndrome becomes clinically apparent.

Nelson’s syndrome

Hyperpigmentation and pituitary enlargement occur in about 20 per cent of cases after bilateral adrenalectomy and are avoided by selective pituitary microsurgery.

Prognosis. Most patients are alive 20 years after successful resection of an adrenal adenoma, but survival beyond 5 years is rare with a carcinoma (Welbourn). Pituitary microadenectomy in expert hands results in cure in about 80 per cent of patients very rarely, the adrenogenital syndrome appears in youths and men. Owing to excessive production of oestrogenic hormones by the adrenal cortex, gynaecomastia, atrophy of the testicles and psychical signs of effeminacy appear (adrenal feminism).

Postmenopausal hypercorticism

Postmenopausal hypercorticism is usually characterised by the growth of a beard (the bearded woman of the circus) and is often accompanied by mental aberration. A lesser degree of hirsutism is almost a natural accompaniment of the ageing process, particularly in dark-haired females, and it is difficult to draw the line between the normal and the pathological. Thus it is that operative treatment is usually disappointing.

Primary aldosteronism

Primary aldosteronism (Coon’s syndrome) is a surgically correctable type of hypertension found in 1—2 per cent of all hypertensive patients. It is characterised by autonomous excessive aldosterone secretion which leads to sodium retention and a fall in serum potassium. The latter causes the typical associated features of the syndrome, namely episodes of muscular weakness associated with polyuria and polydipsia. The plasma sodium is high and the potassium is low, but simple administration of potassium does not relieve the condition. Renin and angiotensin levels are depressed. The cause is either an aldosterone­secreting adrenal adenoma or bilateral adrenocortical hyperplasia (less common). CT and adrenal scanning with radioactive-labelled cholesterol are the appropriate localisation tests to distinguish between them. When these fail, adrenal venous sampling with measurement of aldosterone to cortisol ratios is the next step. Unilateral adrenalectomy is the treatment for an aldosterone-producing adenoma and has a high cure rate, whereas surgery has been disappointing in adrenocortical hyperplasia and these patients are generally managed medically.

  Secondary aldosteronism

Secondary aldosteronism is associated with cirrhosis of the liver, and renal artery stenosis with high levels of renin and angiotensin.

The incidental adrenal mass ‘incidentaloma’

CT and MRI have resulted in increasing numbers (up to 1 per cent) of adrenal tumours being identified in the course of abdominal imaging for the investigation of other conditions. The finding may represent an adrenal tumour but more probably a benign lesion. Opinion is divided about management but essentially functioning lesions are excised whereas nonfunctioning lesions are managed according to size. Lesions less than 3 cm in size should be followed 3-monthly for a time by CT and excised if they enlarge, whereas those larger than 3 cm should be excised to exclude malignancy.

Adrenalectomy for hypercorticism

It is essential that all patients who are to be subjected to adrenalectomy are supported intra operatively and postoperatively by adrenocortical hormone replacement therapy, irrespective of the extent of adrenal resection.

Corticosteroid therapy

Corticosteroids are started when anaesthesia is induced. There is no advantage of one steroid over another except for their different durations of action. Hydrocortisone is very short acting, prednisolone intermediate and dexamethasone long acting. Each may be given intravenously or intramuscularly.

During the first 24 hours after induction of anaesthesia, the patient should receive no more than 300 mg hydrocortisone, 60 mg prednisolone or 6 mg dexamethasone. The dosage should be halved each day until a maintenance dose orally (hydrocortisone 30 mg, prednisolone 5 mg or dexamethasone 0.5 mg) is reached. Fludrocortisone 0.1 mg daily (replacing aldosterone) is usually added to the maintenance dose of corticosteroid to regulate fluid and salt balance.

After total adrenalectomy the patient should always carry a card stating the dosage of corticosteroid being received. Any stress (e.g. further operation or infection) is an indication to increase the dosage.

Operation

When an adrenal tumour has been demonstrated pre­operatively, excision of that adrenal gland alone is carried out.

Posterior approach

An ample posterolateral incision, such as is used for nephrectomy (Chapter 64), is used. After subperiosteal resection of the 12th rib, the lower border of the pleura is defined and protected. The incision is extended through the bed of the 12th rib to reveal the perinephric fat, within which the adrenal gland is identified, as described below. Sometimes an approach through the bed of the 11th rib, reflecting the pleura upwards, is preferred. (See also Anterior approach, below.)

On the right side the suprarenal vein is short and may be torn from the vena cava if it is not identified and ligated at an early stage of the dissection. By finger and gauze dissection, keeping close to the gland, the gland is freed from below and behind, upwards, ligating and dividing bleeding vessels as they are encountered, until it is suspended only by its main vascular pedicle near its apex.

Anterior approach

The adrenal glands are approached through either a curved transverse incision or a long midline incision. The left adrenal gland is approached first by cutting along the lateral leaf of the lienorenal ligament and then curving downwards and medially, so as to enable a wide peritoneal flap to be reflected. By retracting the spleen downwards and medially, the adrenal gland comes into view. The fascia over its lateral border is -incised, and by gauze dissection the blood vessels of the gland are defined, ligated and divided, thus freeing the gland, which is removed. Alternative approaches can be made by an ‘up and under’ dissection of the mesocolon and pancreas, or through the lesser sac. The right adrenal gland is more deeply situated. The peritoneum is incised lateral to the duodenum and above the upper pole of the kidney. The flap of peritoneum is raised to expose the anterior surface of the adrenal gland as it lies against the bare surface of the liver. The fascia covering the lateral surface of the gland is incised. A finger can then be inserted above the upper pole of the gland into the space between the two layers of fascia enclosing the gland (Fig. 45.11). This prevents the gland from becoming displaced upwards, which otherwise it is prone to do. The anterior fascial layer is then incised transversely and the gland can be dissected under vision, as on the left side. After removal, each gland should be inspected to check its completeness, and each adrenal bed must be searched for the presence of accessory adrenal tissue, which is present in 32 per cent of cases. If this important step is omitted, failure of the operation is not unlikely.

Thoracoabdominal approach

For removal of a large adrenal tumour (>10—15 cm in diameter) a thoracoabdominal incision gives the wide exposure necessary for radical resection en bloc which may involve removal of the ipsilateral kidney or spleen and tail of the pancreas.

Laparoscopic adrenalectomy

Laparoscopic adrenalectomy is a developing technique which may in selected patients, particularly patients with Coon’s syndrome, provide an alternative operative approach using a full lateral decubitus transperitoneal flank approach. It is claimed that such a technique offers a less painful postoperative recovery, with the in-patient stay reduced from a mean of 8 days for open surgery to 3—4 days. This must be offset against a doubling of the operating time, a possible increased incidence of wound infection and port site hernia formation.

Left adrenalectomy. Start by dissecting the splenoparietal ligament close to the diaphragm to permit a complete mobilisation of the spleen to the right with the tail of the pancreas. Dissection of 5 cm of the splenic vein, when used as a landmark, permits exposure of the renal vein: which leads to the main and accessory adrenal veins. They can be safely divided between clips. The right side of the gland is dissected up to the diaphragm with clipping of the middle and upper arterial pedicles. The adrenalectomy is achieved by dissection of the fat and the gland is extracted in a bag.

Right adrenalectomy. The fundamental step of the procedure is the section of the hepatoparietal ligament far to the right allowing an upwards mobilisation of the liver. Then dissect towards the vena cava using this structure as a landmark to find the renal vein which is the inferior limit of the dissection. The main adrenal vein is doubly clipped and divided. The third step is to look for an accessory adrenal vein joining a subhepatic vein above the main adrenal vein. The adrenal arteries, superior, middle and the main inferior one coming from the renal artery, are dissected on the right side of the vena cava. The last step is straightforward coagulation, vessel clipping and dividing as on the left side.

Adrenal medulla

Physiology. The medulla of the adrenal glands (chromaffin tissue), which is developed, together with sympathetic nerves, from ectoderm, is grey in colour and connected intimately, both anatomically and functionally, with splanchnic nerves. Chromaffin tissue is so called because the large polyhedral cells of which it is composed contain granules that stain yellow with chromic acid. These granules are the internal secretion of the adrenal medulla itself, for they can be observed being extruded in toto into radicles of the adrenal vein. The secretion consists of the catecholaminest, adrenaline and noradrenaline. In health, 80 per cent of the output is adrenaline and 20 per cent is noradrenaline. However, in hyper functioning medullary tumour (phaeochromocytoma) this ratio is completely reversed. Fear, anger, pain and effort give rise to an increased output in response to the stimuli received via the splanchnic nerves.

An amino acid peptide adrenomedullin has recently been isolated from human phaeochromocytoma. It has a structure similar to calcitonin gene-related peptide and amylin. Intravenous administration elicits a strong, long-lasting hypotensive effect. It has been detected in human plasma and vascular smooth muscle cells with specific receptors. It decreases blood pressure by lowering total peripheral resistance and increasing urine flow and urinary sodium excretion.

Actions of catecholamines. Catecholamines exert their effects through specific cell-surface receptors: alpha-receptors and beta-receptors (Table 45.1). These mediate the actions of the endogenously released catecholamines, noradrenaline and adrenaline, and some of the actions of dopamine. The receptors have quite different pharmacological properties and an organ may have more than one type. The complex actions of catecholamines include altering enzyme activity, metabolic pathways and the permeability of cell membranes to ions.

Pharmacological inhibitors of alpha stimulation (alpha-blockers) include the long-acting phenoxybenzamine (Dibenyline) and short-acting phentolamine (Rogitine). Beta-blockers include propranolol (Inderal) and practolol (Eraldin).