ADRENAL

DISORDERS

Presenter:
L.Kobusinge
Outline
• Anatomy and physiology.
• Disorders of the adreanl cortex
Incidentaloma
Primary hyperaldosteronism(Conn’s syndrome)
Cushing’s syndrome
Adrenocortical carcinoma
Congenital adrenal hyperplasia(adrenogenital syndrome)
Adrenal insufficiency (acute and chronic)
• Disorders of the adrenal medulla and neural crest-deived tissue
Phaeochromocytoma and paraganglioma
Neuroblastoma
Ganglioneuroma
ANATOMY
Weight = 4g
2 adrenal gland, right and
left.
2 component ; inner adrenal
medulla and outer adrenal
cortex.
Situated near upper poles of
kidneys in retroperitoneum,
within Gerota’s capsule.
Anatomy..
• Right adrenal gland
– between right liver
lobe and diaphragm.
• Left adrenal gland – close
to upper pole of left kidney
and renal pedicle, covered
by pancreatic tail and
spleen.
 Anatomy..
Arterial blood supply
–superior suprarenal artery
(from inferior phrenic artery).
-middle suprarenal artery
(from abdominal aorta).
- inferior suprarenal artery
(from renal artery).
Anatomy..
Venous blood supply
–Right suprarenal veins
drain into inferior vena cava.
- Left suprarenal vein drain
into left renal vein or left
inferior phrenic vein.
Histology
• Adrenal cortex : Arranged in zonal configuration
🞑 Outer zona glomerulosa = small, compact cells
🞑 Central zona fasciculata = larger, lipid-rich cells arranged in radial
columns
🞑 Inner zona reticularis = compact & pigmented cells

• Adrenal medulla
🞑 Thin layers of large chromaffin cells which synthesise, store and
secrete catecholamines.
FUNCTION
Disorders of the adrenal cortex
1. Incidentaloma
2. Primary hyperaldosteronism(Conn’s syndrome)
3. Cushing’s syndrome
4. Adrenocortical carcinoma
5. Congenital adrenal hyperplasia(adrenogenital syndrome)
6. Adrenal insufficiency (acute and chronic)
1. Incidentaloma
Is adrenal mass, detected incidentally by imaging studies conducted for other
reasons, not known previously to have been present or causing symptoms.
Incidence
The prevalence in autopsy studies is
in the range of 1.4 to 8.7%.
It increases with age.
Prevalence is 1% on imaging studies.
More than 75% are non-functioning
adenomas.
Diagnosis …to exclude functionality and malignancy
• Complete history.
• Complete examination.
• A biochemical work-up for hormones.
Morning and midnight plasma cortisol measurement.
A 1 mg overnight dexamethasone suppression test.
24 hour urinary cortisol excretion.
12 or 24 hour urinary excretion of metanephrines or plasma free metanephrines.
Serum K, plasma aldosterone and plasma renin activity.
Serum DHEAS, testosterone OR 17-hydroxyestradiol (virilising or feminizing
tumor)
Diagnosis…
• Imaging studies; shd be done in all patients with adrenal masses.
MRI
CT
• Biopsy to confirm suspected metastasis from a distant primary site.
NB; Never biopsy an adrenal mass until pheochromocytoma has been
biochemically excluded.
Treatment
• Surgical resection,
For a non functioning tumor <4 cm in diameter and smaller tumors
that increase in size over time.
• Non functioning tumors smaller than 4 cm should be followed after 6,
12 and 24 months by imaging MRI and hormonal evaluation.
2. Primary Hperaldosteronism (Conn’s
syndrome)
• Hypertension as a result of hyper secretion of aldosterone.
• In PHA, plasma Renin activity is suppressed.
The incidence of PHA is approximately 2% in patients with hypertension.
Pathology
The most frequent cause of PHA with hypokalemia is unilateral adrenocortical
adenoma.
In 20-40% of cases, bilateral micro nodular hyperplasia, glucocorticoid
suppressible hyperaldosteronism or adrenocortical carcinoma.
Some patients with normal kalaemic PHA, 70% have hyperplasia and 30%
unilateral adenoma.
Conn’s syndrome is characterized by increased aldosterone secretion from the adrenal
glands, suppressed plasma renin activity (PRA), hypertension,and hypokalemia.
 Clinical Features
• Most patients are between 30 and 50 years of age with female
predominace.
• Hypertension
• Headache
• Muscle weakness
• Cramps
• Intemitent paralysis
• Polyuria
• Polydypsia
• nocturia
Diagnosis
• Biochemical, aldosterone to plasma renin activity ratio, K levels
Antihypertensive and diuretic therapy which cause hypokalaemia and influence the Renin-
Angiotensin-Aldosterone system have to be discontinued.
• MRI and CT to distinguish unilateral from bilateral diseases.
• Conn’s adenoma usually measure 1-2 cm.
• Micronodular changes and small adenomas are often undiagnosed.
• Aldosterone to Cortisol ratio
Treatment
• Medical; spironolactone. Is the first line treatment for PHA with
bilateral hyperplasia.
• Supplemental antihypertensive
• Unilateral laparoscopic adrenolectomy for unilateral and
asymmetrical bilateral disease.
• Subtotal resection can be considered in case of atypical single Conn's
adenoma.
3. Cushing syndrome
• Hyper secretion of cortisol caused by endogenous production of
corticosteroids.
• It can be either ACTH-dependent or ACTH-independent in origin.
• ACTH-dependent Cushing's disease resulting from pituitary adenoma that
secrets an excessive amount of ACTH.
• Ectopic ACTH-producing tumors (small cell lung carcinoma, foregut carcinoid)
and CRH-producing tumor (medullary thyroid carcinoma, neuroendocrine
pancreatic tumor)
• ACTH-dependent Cushing's can be due to prolonged administration of
cortisol-like drugs
• ACTH-independent is cause by unilateral adrenocortical adenoma.
Differentials
• Adrenocortical carcinoma
• Bilateral macro nodular or micro
nodular hyperplasia.
Diagnosis
• Morning and midnight plasma cortisol levels are elevated possibly
with loss of diurnal rhythm.
• Dexamethasone fails to suppress 24 hour urinary cortisol excretion.(D
examethasone suppression test)
• Serum ACTH levels distinguishes ACTH-dependent from ACTH-
independent.
• MRI of the pituitary in case of elevated ACTH.
• Abdominal and chest CT for ectopic.
 Treatment
• Medical; metyrapone or Ketoconazole reduces steroid synthesis and
secretion and can be used to prepare patients with severe
hypercortisolism preoperatively.
• If an ectopic ACTH source is localized, resection will correct
hypercortisolism.
• ACTH- producing pituitary tumors are treated by trans-sphenoidal
resection or radiotherapy.
• Bilateral adrenectomy in case of bilateral ACTH-independent.
• subclinical Cushing's syndrome caused by unilateral adenoma is treated
by unilateral adenalectomy.
Preoperative management
• Prophylactic anticoagulant and antibiotics.
• Control of cushings associated diseases (diabetes and hypertension)
Post operative management
• Supplemental cortisol after adrenalectomy (I.V hydrocortisone 15
mg/hour for first 12 hours.
• Then tabs hydrocortisone 100mg od for 3 days which is gradually
reduced thereafter.
NB: Pituitary adenoma causes Nelson’s syndrome due to continued
ACTH secretions at high levels causing hyperpigmentation due to
chemical synergies between ACTH and melanocyte-stimulating
hormone.
Adrenal Metastasis
• Are discovered at autopsy in a third of patients with malignant
diseases like breast, lung, renal, gastric, pancreatic, ovarian and
colorectal cancers
4. Adrenal cortical carcinoma
• Rare malignancy with an incidence of 1-2 cases per 1000000 population
per year.
• Slight female predominance.
• Bimodal age distribution with first peak in childhood and second peak in
the fourth and fifth decades.
Pathology
• Criteria for malignancy are tumor size, the presence of necrosis or
hemorrhage and microscopic diagnostic score.
• Macroscopic features: multimodality and heterogeneous structures
with hemorrhage and necrosis.
Clinical features
• Cushing syndrome
• Patients with non-functioning tumor frequently complain of abdominal discomfort or
back pain caused by large tumors.
• Detected incidentally by abdominal imaging.
• Feminizing /muscularizing steroids.

Diagnosis
• Measure of DHEAS, Cortisol and catecholamine
• Dexamethasone suppression test.
• MRI angiography to exclude tumor thrombus in the inferior venacava
• CT , for staging.
WHO CLASSIFICATION OF AND
STAGING
• Based on McFarlane classification
Tumor ˂5cm stage1
Tumor ˃5 cm stage II
Tumor locally invasive stage III
Distant metastasis stage iv
Functioning tumor tend to do more worse than non-functioning tumors
with metastasis but have advantage of serum markers which can be
used for follow and monitoring of the disease.
Treatment
• Complete tumor resection. The capsule must not be damaged to
prevent metastasis and spillage.
• Thrombectomy in case of thrombus in the venacava.
• Laparoscopic adrenectomy. This is associated with recurrence.
• Tumor debulking to control hormonal excess.
• Patients treated postoperatively with mitotane alone or combined
with topside, doxorubicin and cicsplastin.
• Adjuvant radiotherapy may reduce the rate of local recurrence.
• Restaging after every three months to monitor relapse.
Prognosis
• Depends on the stage of the disease and complete removal of the
tumor.
• Patients with stage I and II, their 5 year survival rate is 25%.
• Those with stage III and IV, their 5 year survival rate is 6 and 0%
respectively.
5. Congenital Adrenal Hyperplasia
(Adrenogenital Syndrome)
• Virilisation and adrenal insufficiency I children are pathognomic of
CAH.
• This is an autosomal recessive disorder caused by a variety of
pathology of cortisol and other steroids cholesterol.
• The most frequent defect is 17-hydroxylase deficiency, which has an
incidence of 1 in 5000 live births.
• Excessive ACTH secretion is caused by the loss of cortisol and this
leads to an increase in androgenic cortisol precursor thus CAH.
Presentation
• CAH can present in girls a birth with ambiguous genitalia or late onset
disease at puberty
• Hypertension and short stature caused by premature closure of
epiphyseal plate.

Treatment
• Patients are treated by replacing cortisol and with fludrocortisone.
• Large hyperplastic adrenals may need to be removed if symptomatic.
6. Adrenal Insufficiency
• Primary adrenal insufficiency is caused by loss of function of the
adrenal cortex.
• Early diagnosis is a clinical challenge. Symptoms are only evident
when about 90% of the adrenal cortex is destroyed.
• Secondary adrenal insufficiency is defined as a deficiency of pituitary
ACTH secretion.
• Tertiary adrenal deficiency is provoked by a loss of hypothalamic CRH
secretion and is caused by therapeutic glucocorticoid administration,
brain tumor or irradiation.
Affects both mineralcorticoids and glucocorticoids
Acute Adrenal Insufficiency
• Presents with shock in combination with fever, nausea, vomiting,
abdominal pain, hypoglycemia and electrolyte imbalance.

• The Waterhouse Frederickson Syndrome is a bilateral adrenal infarction

associated with meningococcal sepsis and is rapidly fetal unless
immediately treated.
Chronic Adrenal Insufficiency

The Addison’s disease presents with anorexia, weakness and nausea.

• As a result of negative feedback, ACTH and pro-opiniomelanocortin
(POMC) levels increase and cause hyperpigmentation of the skin, oral
mucosa.

Hypotension., hyponatremia, hypokalemia and hypoglycemia are

commonly observed.
Diagnosis
• Done by using ACTH stimulation test.
Basal ACTH levels are found to be high with cortisol levels decreased.
There is a rise in cortisol levels following exogenous administration of
ACTH (Synacthen test)
Treatment
• Acute Adrenal Insufficiency is an emergency.
• Treat with iv hydrocortisone 100mg 6 hourly.
• 3 liters of saline in 6 hours.
• Monitor for CVS
• Treat infection
• Chronic adrenal insufficiency are treated by replacement therapy with daily
oral hydrocortisone 10mg/m2 body surface area and fludrocortisone 0.1mg.
• Counsel patients about life long glucocorticoid and minerocorticoid use.
• To prevent an Addisonian crisis, patients must be aware of the need to
increase the dose in case of illness or stress.
Disorders of the adrenal medulla and
neural crest-derived tissue

1. Phaeochromocytoma and paraganglioma

2. Neuroblastoma
3. Ganglioneuroma
1. Phaeochromocytoma and
Paraganglioma
• These are tumors of adrenal medulla and sympathetic ganglia which
are derived from chromaffin cells and which produce catecholamine.
Phaeochromocytoma
Aetiology
• Phaeochromocytoma is known as the 10% tumor;
• 10 % of the tumor are hereditary.
• 10% are extra adrenal
• 10% are malignant
• 10% are bilateral
• 10% occur in children.
Aetiology …
Hereditary phaeochromocytoma occur in several tumor syndromes;
• Multiple endocrine neoplasia type 2 (MEN2). This is an autosomal
dominant inherited disorder tat is caused by activating germ line
mutations of RET proto-oncogene.
• Familial paraganglioma (PG) syndrome. Glomous tumor of carotid body
and extra adrenal paraganglioma. Its caused by germ mutation within
the succinate dehydrogenase complex subunit B (SDHB), SDHD and
SDHC genes.
• Von Hipple-Lindau (VHL) syndrome. Those affected can develop early
onset bilateral kidney tumor, phaeochromocytoma, cerebellar and spinal
haemangioblastoma and pancreatic tumors.
Etiology continue……..
• Neurofibromatosis (NF) type 1 phaeochromocytoma in combination
with fibromas on the skin and mucosae (Café au-lait skin spot) are
indicative of a germ line mutation in the NF1 gene.
Pathology
• Phaeochromocytomas are greyish-pink on the cut surface and are
usually highly vascularized.
• Areas of hemorrhage or necrosis are often observed.
• Microscopically, tumor calls are polygonal but the configuration varies
considerably.
• The differentiation between benign and malignant tumors is difficult
except if metastasis is present.
• Phaeochromocyoma may also produce calcitonin, ACTH, Vasoactive
intestinal polypeptide (VIP) and parathyroid hormone- related protein
 Diagnosis
• Determination of adrenaline and noradrenaline breakdown products,
metanephrine and normetanephrine levels in a 12or 24 hour urine
collection.
• Determination of plasma free metanephrine and normetanephrine levels.
• Biochemical tests should be performed at least twice.
• MRI to localize the phaechromocytoma. Contrast media in CT can trigger
paroxysms.
• Classically phaeochromocytoma mass show a Swiss cheese configuration.
• Single photon emission computed tomography (SPECT) for extra-adrenal
tumors and metastasis.
• PET scanning using FDG PET or DOPA PET for detecting metastatic foci.
Treatment
• Laparoscopic resection
• If the tumor is larger than 8-10 cm or radiological signs of malignancy
are detected, an open approach should be considered.
 Preoperative
• Administration of alpha adrenoceptor blockers (phenoxybenzamine) is
used to block catecholamine excess and its consequence during surgery.
20 mg daily of phenoxybenzmine initially. The dose is increased daily until
a daily does of 100-160 mg is achieved and postural hypotension.
• Additional beta blockade is required if tachycardia or arrhythmias
develop.
• Central venous catheter and invasive arterial monitoring .
• Administration of vasodilators agents in case of change in heart rate and
blood pressure.
• The infusion of large volumes of fluid or administration of noradrenaline
can be necessary to correct postoperative hypotension.
Post operative
• Patients should be observed in ICU for 24 hours for hypovolemia and
hypoglycemia.
• Life long biochemical tests should be performed to identify recurrent
metastatic or metachronous phaeochromocytoma
Malignant Phaeochromocytoma
• Approximately 10% of phaeochromocytoma s are malignant. This rate is
higher in extra-adrenal tumors (paraganglioma).
• The diagnosis of malignancy implies metastases of chromaffin tissues, most
commonly lymph nodes, bones and liver.

Treatment
• Surgical excision.
• Tumor debulking.
• Symptomatic treatment can be obtained with alpha blockers.
• Mitotanes should be started as adjuvant or palliative treatment.
Phaeochromocytoma in pregnancy
• It may imitate an amnion infection syndrome or pre-eclampsia.
• Without adequate alpha blockade, mothers and unborn children are
threatened by hypertensive crisis during delivery.
• In first and second trimesters, the patient should be scheduled for
laparoscopic adrenalectomy after adequate alpha blockade. The risk
of miscourage during surgery is high.
• In the third trimester, elective caesarean with conservative
adrenalectomy should be performed.
• Maternal mortality rate is 50% when phaechromocytoma remains
undiagnosed.
2. Neuroblastoma
• Is a malignant tumor that is derived from the sympathetic nervous
system in the adrenal medulla or from any site along the sympathetic
chain on the paravertebral sites of the abdomen, chest and rarely
neck and pelvic.
Pathology
• Have a pale and grey surface.
• Are encapsulated.
• Shows areas of calcification.
• With increase tumor size, necrosis and hemorrhage may be detected.
• They are characterized by the presence of immature cells derived from the
neuroectoderm of the sympathetic nervous system. Mature cells are found only in the
ganglioneuroblastoma.
Presentation
Predominantly newborn infants and children ˂5years of age are affected.
Symptoms are caused by tumor growth or by bone metastases.
Patients present with a mass in the abdomen, neck, chest ,proptosis, weakness, paralysis.
Diagnosis
• 24 hour urine collection for Vanillylmandelic acid (VMA),
Hemovanillic acid (HVA), Dopamine and noradrenaline as increased
levels are suggestive.
• Accurate staging requires Ct or MRI of the chest and abdomen.
• Bone scan.
• Bone marrow aspiration.
• Core biopsy
• MIBG scan
 Treatment
• Prognosis can be predicted by the tumor stage and the age at diagnosis.
• Patients are classified as; low, intermediate or high risk.
• Low risk patients are treated surgery alone.
• Intermediate risk patients are treated by surgery with adjuvant multi agent
chemotherapy (carboplatin, etoposide, cyclophosphamide, doxorubicin)
• High risk patients receive high dose multi agent chemotherapy followed by
surgical resection in responding tumors and myeloablativestem cells
• The prognosis of low, intermediate, and high risk patients is 90,70,30%
respectively.
3. Ganglioneuroma
• A begnin neoplasm that arises from neural crest tissue.
• It occurs in adrenal medulla and are characterized by mature sympathetic ganglion cells and
Schwann cells in fibrous stroma.

Clinical features
• Are found in all ages but more common before 60 years of age.
• Occur any where along the paravertebral sympathetic plexus and in adrenal medulla.
• Most often they are identified incidentally by CT or MRI performed for other indications.

Treatment
• Surgical excision
• Laparoscopic when adrenalectomy is indicated.
Reference.
• Bailey and Love 27th edition