THE ADRENAL GLANDES

PROF. Atif M. Abdellatif, MD

Professor of General & Endocrine Surgery
Founder of Mansoura Endocrine Surgery Unit

Fig 1.22 : anatomy of adrenal glands

Development and Histology :

The adrenal cortex is developed from the cephalic end of the Wolffian body. The

cortex consists of 3 layers :

(i)Zona glomerulosa

(ii)Zona fasciculata

(III)Zona reticularis.
 The cells of zona glomerulosa manufacture aldosterone. The cells of fasciculata and

reticularis manufacture cortisol, corticosterone, androgen and oestrogen.

The medulla contains chromaffin tissue, allied to that of sympathetic ganglion. Both

the adrenal medulla and sympathetic ganglions are developed from neuroectoderm.

Surgical Anatomy: (Fig 1.22)

–The adrenal glands, two in number, are situated on the upper pole of each kidney in a

separate compartment of renal fascia, behind the peritoneum. They are identified by their

deep yellow colour. The right suprarenal gland is triangular in shape. It lies behind the

liver, medial to inferior vena cava, and in front of right crus of the diaphragm. The left

one is semilunar in shape. It lies behind the stomach and splenic artery, in front of left

crus of the diaphragm .

Surgical Physiology :
–The adrenal cortex secretes about 50 steroid compounds. They may be classified under

three groups :

(A) Mineralocorticoids ( Sodium retaining hormones ) :

– They are concerned with water and salt metabolism. This form of adrenocortical

activity is due to aldosterone . A deficiency of this hormone Results

– In diuresis, potassium retention and dehydration. An increase of this Hormone results

in oedema, hypokalemia and hypertension .

 (B) Glucocorticoids :

–They are concerned with the metabolism of glucose and protein. They have also anti-

inflammatory and anti-allergic actions. Cortisol and corticosterone are responsible for

these effects. With large doses of these Hormones, the blood sugar is raised. Circulating

blood eosinophils and lymphocytes are depleted.

(C) Sex Hormone :

– Both androgenic and estrogenic hormones are produced by the adrenal cortex . In males,

androgen is also produced in interstitial cells of the testis. Excessive secretion of

androgens causes virilism in females.

Relations with other Endocrines :

–The suprarenal cortex is under the control of anterior pituitary (A.C.T.H). The latter

accelerates the secretion of the adrenal cortex. On the other hand, corticosterone of the

adrenal cortex inhibits the secretion of A.C.T.H

Adrenal medulla:
–The adrenal medulla secretes adrenaline and nor-adrenaline in the ratio

Of 4:1. They produce vasoconstriction and rise of blood pressure.

– Both the cortex and the medulla are concerned with the body response to stress
 Investigations in cases of Adrenocortical Function Disorders
A)Tests of adrenocortical activity :
I) Plasma electrolytes :
- In hyperfunction —> Na is increased.
—>K is decreased.
- The opposite occurs in hypofunctioning states.
II) Plasma cortisol levels :
- Loss of diurnal variation.
- In Cushing's syndrome —> all levels are high.
- In Addison's disease —-> low levels.
III) Plasma ACTH levels :
-In adrenal tumors --> low.
- In pituitary lesions and ectopic ACTH production -—> high.
IV)Plasma aldosterone levels :
- The concentration of aldosterone is only one thousandth that of cortisol and both
dietary Na and K. may change the value.

V) Urinary steroid excretion :

- The daily output may be determined by the administration of a small amount of
radioactive labelled cortisol, which is metabolized and excreted, and the urinary
radioactivity is Measured.
- The normal range ——> 5-28mg / 24 hs with high levels in Cushing's syndrome
and low levels in adrenal insufficiency. :
IV) Urinary cortisol excretion:
- The cortisol excretion in a 24-hours urine sample is the best screening test for
adrenocortical oversecretion.
VII)17-oxosteriods or ketosteroids :
 These reflect androgen output,

VIII) Dexamethasone suppression test:

1- Low dose suppression test:.
-normal subjects produce about 30 mg of cortisol / day.
-0.5 mg dexamethasone / 6hrs for 2 days orally will suppress ACTH secretion
with marked decrease in urinary steroid excretion to < 5mg / day however, this
amount will not suppress excessive cortisol production in Cushing's syndrome.
2- High dose suppression test:
-2 mg /6hs over several days .
-In Cushing's disease : suppression to < 50% of baseline.
-NO suppression with adrenal tumor (autonomous) or ectopic ACTH syndrome.

IX) Metyrapone test:

- Differentiates between excess ACTH production and a lesion in the adrenal
cortex
- Metyrapone inhibits the biosynthesis of cortisol —> decreased plasma Cortisol
level —> increase ACTH production —> stimulation of adrenal cortex
- the basal levels of 17-OH-corticosteroids and ketosteroids in urine measured for
2 days.
-750 mg of metyrapone is given / 4hs and 24-hs urine collection is done.
-normal response is 2-4 folds increase in urinary steroids over basal levels.
-diminished response = primary adrenal lesion.

B) Localization :
I) Abdominal or cranial CT or MRI scanning.
II) Angiography or adrenal vein sampling to find out an ectopic source of cortisol.
III) I 131 19 iodocholesterol scanning in localization of large adenomas.
Hyperfunction of the Adrenal Cortex
I)Conn's syndrome—> hyperfunction of zona glomerulosa,
II)Cushing's syndrome —> hyperfunction of zone fasciculata.
lII)Adrenogenital syndrome—> hyper function of zona reticular is.

Conn's syndrome
(Primary aldosteronism)

Aetiology:
1)Simple hyperplasia of The cells of zona glomerulosa.
2) Adenoma or less commonly adenocarcinoma of the zona glomerulosa.
3)Genetic deficiency in 17 hydroxylation, a step which is needed in the formation of
glucocorticoids and sex hormones, so that all available adrenal progesrtone will be
changed into aldosterone which needs 18 hydroxylation.

Physiological Disturbances:
–The excess production of aldosterone will lead to :
1) Excess sodium retention—> hypervolemia —> hypertension .
2)Excess loss of potassium which gives :
a) polyuria
b) hypokalaemia
As a compensatory mechanism for this hypokalaemia . potassium ion diffuse out of the
cells and instead Na & H ions diffuse to inside the cells, thus H ions concentration in the
blood diminishes —> alkalosis —> diminished ionisable calcium—> tetany
Clinical Picture:
–Hypertension

–Polyuria

–Symptoms of hypokalaemia as
–asthenia
–muscular fatigability which may proceed lo flaccid paralysis,
– arrhythmias
– nausea and vomiting
– constipation or even paralytic ileus ,
–Tetany with muscle twitch and carpopedal spasms.
–Oedema is slight or absent.

Investigations
–As investigations in case of adrenocortical functions disorders

Treatment:
I) Aldosterone-producing adenoma—> unilateral adrenalectomy.
II) Adrenocortical hyperplasia —> medical treatment in the form of:
1- Spiror.olactone —> compctctive aldosterone aniagonisl.
2- Amiloride —> K-sparing diuretic.

Secondary Aldosteronism
–Is associated with cirrhosis of the liver and renal artery stenosis with high levels renin
and angiotensin.
 Cushing's Syndrome

Causes of Cushing's Syndrome:-

1-Adrenal Gland:
ACTH-independent adrenocortical tumours e.g autonomous adenoma or carcinoma-
Non-ACTH-dependent primary adrenocortical hyperplasia (rare).
2-Pituitary Gland:
pituitary tumours (Cushing's disease) producing excess ACTH (corticotropin) —
>Bilateral adrenal hyperplasia.
pituitary overactivity due to increased C.R.H, (corticotropin releasing hormone).

3-Extrapituitary ACTH (or ACTH-like substance) producing Tumours

=Ectopic ACTH syndrome.
Bronchogenic Carcinoma ,oat cell carcinoma of the lung, carcinoid tumour, pancreas ,
thymus , thyroid , prostate ,oesophagus , colon , ovarian carcinoma,
4- Patients treated with large doses of cortisone over long periods for non-
endocrine diseases e.g rheumatoid arthritis , transplantation.

Clinical Picture
–Age: 30-40 ys but may occur at younger ages
–Sex: Females commoner than males.

1)Cutaneous manifestations in the from of:

a) Striae rubra : it is dusky red striae, most apparent in the lower part of the
abdomen, thighs , shoulder and around the breasts . They are caused by rupture of
subcutaneous tissue and they stain red because of the polycythaemia
b) Acne.
 c) Hirsutism : appearance of hairs in females in areas where hair should not be found
as the upper lip, chin and on The shoulder .
d) Cutaneous patchy hyperpigmentation may occur .
2) Hypotonia and weakness of the body muscles :
–Weakness of the abdominal muscles leads To a pot belly abdomen .
3) Osteoporosis of bones :
–This causes generalized aching pain ail over the body which may be
–mistaken for rheumatic pains, the spine will show dorsal kyphosis .
4) Gonadal dysfunction :
–Males suffers from impotence and females from amenorrhea.
5)Steroid diabetes:
– Which will lead to the usual triad of polyuria, polydepsia and polyphagia This type
of diabetes is insulin resistant.

Investigations :
–As investigations of adrenocortical function disorders.

Treatment:
A Medical Treatment:
1 -Temporary control with ketoconazole . metyrapone or amino-glutethimide which
inhibit steroid biosynthesis, can be used for prolonged periods in patients with benign
adrenocortical tumours when immediate surgery is contraindicated .
2- Mitotane (Lysodren) = selectively and reversibly destroys the zona fasciculata and
reticularis but not the zona glomerulosa.

B) Pituitary Ablation or Excision of Adenoma :

1- Irradiation of pituitary adenoma or yttrium 90 implantation takes 8- 18 months before
significant effects arc achieved & recurrences arc common.
2- Microsurgical excision of pituitary adenomas (trans-sphenoidal)
C) Adrenalectomy
I) Adenoma :
—> Excision
II) Bilateral Adrenal hyperplasia:
—> Total or partial adrenalectomy
III) Carcinoma :
—>Extensive dissection & wide excision
D) Ectopic A CTH Syndrome
tumour excision
extensive tumour growth ; palliative chemotherapy.

Adrenogenital Syndrome

Aetiology:
–Hyperfunction of the zona reticularis which may he caused by :
1) Simple hyperphasia
2) Adenoma and less commonly adenocarcinoma .
3) Genetic enzymatic block at 21 and 11 b hydroxylation :
– These steps are needed for the biosynthesis of gluco- and mineralocorticoids and so
their synthesis is depressed and all available adrenal progesterone will thus be changed
to adrenal sex hormones-
Clinical Picture:
– It depends according to the age of appearance of the disease and the sex Of the patient.

1)Neonatal adrenogenital syndrome :

a) If affecting female infant ( commonest):
—> female pseudohermaphroditism.
The born infant is genetically a female because it has female Chromosomes,
ovaries, fallopian tubes, uterus and vagina, but the external Genitalia
resembles those of a male e .g . clitoris is big resembling a penis the 2 labiae
majora are big or even united together resembling the scrotum.
b) If affecting a male infant (rare):
—>macrogenitosomia precox (premature enlargement of sex organs).

2-Pre-pubertal adrenogenital syndrome:

a) if affecting a male child ( commonest) --> precocious puberty .
The child will show rapid appearance of the secondary sex characters as
enlargement of the penis and hyperpigmentation of the scrotum. Sex potency is
also present, muscular strength of child increase hence the term infant Hercules.
The height of the child rapidly increase by the effect of androgens hut only for a
while after which premature closure of epiphysis occurs and so in due time the
child appear to be shorter than others. This type of precocious puberty is a false
one because the testicles remain small (testicles depend on pituitary
gonadotrophin).
b) If affecting a female child ( rare ) :—> primary amenorrhea with delayed or no
puberty .
3)Post pubertal adrenogenital syndrome :
a) If affecting female ( commonest) it causes :
 1) Hirsutism with appearance of mustache , beard , hairs on shoulders and thighs
and body hair is increased .
2) Masculinization
3) Amenorrhea.
4) Psychologic troubles and sex aberration.
b) If affecting male (very rare) : —> feminization and obesity may occur.
Treatment:
I) Surgical treatment:
1-Excision of tumor.
2- Bilateral subtotal adrenalectomy.

II)Medical treatment: (for causes of simple hyperplasia). Prednisone 20 mg/day.

Suprarenal Gland Hypofunction of the

Addison’s Disease
Chronic Suprarenal Insufficiency
Aetiology:
Bilateral destruction of suprarenal glands . This may be caused by:
1) Autoimmune disease (60%).
2) Bilateral tuberculosis of suprarenal glands,
3)Amyloidosis.
 4) Sarcoidosis.
5)Metastatic carcinoma.
6)Hemochromatosis (Bronzed diabetes).
Clinical picture: (fig 1.23)
Onset : gradual
Course: slowly progressive , but the patient is liable to develop acute exacerbations
known as Addison's crisis.

Symptoms and Signs:

1) Marked asthenia (cardinal manifestation):
2)Hypotension (cardinal manifestation).
Pathogenesis :
a. Hyponatraemia.
B. Diminished production of noradrenaline.
3)Hypoglycaemia (cardinal manifestation) :
Pathogenesis :
a. Diminished glucocorticoids .
b. Diminished adrenaline.
4)Hyperpigmentation of the skin and mucous membrane :(cardinal
manifestation ) .
Hyperpigmentation of the skin take one of the following distribution.
a) Generalized tanning of the skin particularly parts exposed to the sun
b) Coffee' au-lait patches of pigmentation .
c)Hyperpigmentation of scars e.g. umbilicus.
d) Hyperpigmentation of the normal pigmentary area as areola, axilla and
scrotum .
-Hyperpigmentation of the mucous membranes :
 Coloured patches of pigmentation occurs in the mucous membranes of the
lips, mouth and vagina .
pathogenesis :
a) increased melanocyte stimulating hormone .
b)diminished formation of adrenaline- and nor-adrenaline
5)Renal manifestations :
a) polyuria : due to excess renal loss of Na .
b) Lack of immediate response to water load due to Hyponatraemia,
c) Pain and tenderness in the renal angles may be present (TB).
6)G.I. manifestation :
vomiting are common and probable due to hyperkalemia.
7)Increased tendency to develop allergic reaction .
 Fig 1.23 Clinical picture of Addison's disease
Investigations:
–As investigations of adrenocortical function disorders .

Treatment :---> Medical

– In long term management, most patients require 20-30 mg hydrocortisone in divided
doses, with fludrocortisone 0.1 mg daily as mineralocorticoid replacement.
– Anti-tuberculous chemotherapy in relevant cases of TB.

Tumors of the Adrenal Medulla

Tumors of the adrenal medulla are classified as follows :

1- Neoplasms of the sympathetic neurones:
a) Ganglioneuroma
b) Neuroblastoma
2- Neoplasms of chromaffin cells
Pheochromocytoma

Pheochromocytoma
It is a tumour of adrenal origin produce both epinephrine & norepinephrine it is called
the 10% tumour because:
1-10 % are bilateral & usually associated with MEN IIa, IIb syndrome & rarely the Voil
Hippel Landau syndrome.
2-10 % are malignant & not easily distinguished from benign tumour except in locally
aggressive or metastatic tumour.
3- 10 % are multiple.
4- 10 % are familial.
5- 10 % occur in children.
6- 10 % are of extraadrenal origin & produce pure norepinephrine e.g any where along
the paraganglionic system e.g organ of Zuckerkandl at the aortic bifurcation , urinary
bladder, renal hilum chest & neck (have a higher incidence of malignancy).

Pathology
 soft vascular tumour usually < 5 cm in diameter.
 usually pink tan in colour.
 composed of large , differentiated , sympathetic gangloin cells &few fibres
enclosed in a delicate capsule , chromaffin granule.
 occurs in both sexes.
 usually during early adult life or middle age.

Clinical picture
 Atypical complaint is that of fear (I thought I was going to die ).
 Paroxysmal or persistent (especially in late stage ) hypertension associated
with :
 sweating , palpitation , pallor
 vomiting , headache & weakness
 dyspnea , cardiac failure , encephalopathy
 hyperglycemia may present
 >>>the paroxysmal attacks vary from few minutes to hours
Investigations
1-urinary catecholamines excretion & its metabolites
Normal values
- free catecholamines < 100 mg/ 24 hr.
- vanillyl mandelic acid (V.M.A) < 7 mg / 24 hr.
- metanephrines (metadrenalines) < 1.5 mg I 24 hr.
False + ve results may occur in patients taking MAO inhibitors & who have recently
had angiographic contrast studies
- epinephrine < 100 mg / 24 hr
- norepinephrine < 25 mg/24hr

2- plasma level of catecholamines

>l000 mg/ml
– more sensitive & accurate however, may not be continuously
–elevated & many factors including exercise , severe illness &methyl dopa may
influence the levels.

3- Localization of The Tumour

1- CT Scanning has excellent specificity & sensitivity
2- ultra sound scanning
3-I.V.U.
4- Angiography
5- Selective venous sampling.
6-Radionucleide scanning
– particularly in locating ectopic pheochromocytoma
– iodine labelled Metaiodobenzyl Guanidine (MIBG) specific for
catecholamine precursors.
 – only abnormal areas of adrenergic tissue show uptake of MIBG & normal
adrenals do not visualize.
7- Transcatheter brush biopsy of I.V.C. tumour thrombi.

Differential Diagnosis
1- hyperthyroidism
2- hypocalcemia
3- acute anxiety state
4- paroxysmal atrial tachycardia
5- carcinoid syndrome.

preoperative preparation
1- fluid & cardiac status monitored & maintained with pulmonary artery wedge
catheterization or C,V, line (all patients will be relatively hypovolaemic requiring
replacement because of the contraction of the vascular bed by excess circulating
catecholamines).
2-phenoxyhenzamine 20-40 mg/day for 1-3 weeks & B. blockers e.g. propranolol for 3-7
days before operation

During operation
1- phenoxybenzamine (adrenergic blocker) & B. blocking agents as determined by blood
pressure , pulse rate & C.V.P.
2-Na-nitroprusside(direct peripheral vasodilator)
3- Lidocaine should be available for arrhythmias.
4- avoid excessive tumour handling and the main adrenal vein ligated first as this may
increase the circulating catecholamines to 600 folds causing very high blood pressure
& cardiac arrhythmia,
5- rupture of the tumour should be avoided as this may result in local spread & recurrence
even in apparently benign Tumours

postoperative
– monitoring of the blood pressure in I.C-U. with the use of volume replacement &
vasopressors (to counteract hypotension secondary to vasodilatation & hypovolaemia ).