The document discusses adrenal gland tumours including adrenal cortical tumours, phaeochromocytoma, neuroblastoma, and Cushing's syndrome. Key points are:
1) Adrenal cortical tumours can be functioning or non-functioning adenomas. Incidentalomas are adrenal tumours found incidentally on imaging and require hormone evaluation.
2) Phaeochromocytomas arise from chromaffin cells and secrete catecholamines. They present with severe headaches and symptoms of sympathetic overactivity.
3) Neuroblastoma is the most common abdominal tumour in children that arises from adrenal medulla. It has different risk groups and stages that determine prognosis and treatment.
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2. INTRODUCTION
• Adrenal cortex(85%) contains three
layers:
1. Zona glomerulosa secretes
mineralocorticoids.
2. Zona fasciculata secretes
glucocorticoids.
3. Zona reticularis secretes sex
hormones.
• Adrenal Medulla (15%) produces
and secretes norepinephrine,
epinephrine.
3. ADRENAL CORTICAL TUMOURS
• Are usually adenomas.
• Any tumour measuring 6 cm or more are likely to be malignant
• Cortical adenoma may be functioning or nonfunctioning.
• Functioning tumours secrete mineralocorticoids, glucocorticoids or s
sex hormones or combinations of these.
• Investigations: Ultrasound abdomen, CT scan, hormone evaluation.
• Treatment: Adrenalectomy.
4. INCIDENTALOMAS
• Incidentalomas are adrenal tumours incidentally identified either
through Ultrasound, CT scan or MRI.
Diagnostic Test required are :-
• Overnight dexamethasone suppression test
• 24-hour urinary cortisol excretion assay
• 24-hour urinary excretion of catecholamines
• Serum potassium, renin and aldosterone analysis
• MRI in suspected malignancy is better.
• If secondaries are suspected adrenal mass biopsy is done
6. MANAGEMENT
• Non-functioning adrenal tumour >4 cm should be operated.
• Smaller tumours that increase in size over specified period should be
removed.
• All functioning tumours should be operated.
• Non-functioning tumour less than 4 cm should be followed up at
regular intervals by hormone tests and CT/MRI.
7. ADRENOCORTICAL CARCINOMA
• It is a rare malignancy with 1 case in 1000000 population.
• It is common in females with bimodal presentation.
• It is least common malignant endocrine tumour.
• Larger tumours >100 g weight are more likely to be malignant.
• Features of Adrenocortical carcinoma are
1. Tumour size (> 6cm)
2. Necrosis
3. Haemorrhage
4. Capsular & vascular invasion.
5. Immunohistochemistry is specific.
8. CLINICAL PRESENTATION ARE
• Abdominal pain
• Back pain
• Cushing’s syndrome (60%)
• Hyperaldosteronism
• Virilisation
INVESTIGATIONS
Hormone evaluation
CT/MRI
MR angiography to identify IVC tumour thrombus.
HRCT of lungs to detect secondaries in the lungs.
9. MCFARLANE STAGING OF ADRENOCORTICAL
CARCINOMA
Stage I—tumour <5 cm
Stage II—tumour >5 cm
Stage III—tumour with local invasion
Stage IV— distant spread.
10. TREATMENT
• EN BLOCK ADRENALECTOMY is done, where adjacent organs like
kidney, spleen may be removed if needed.
• Removal of tumour thrombus from vena cava if present.
• Chemotherapy using mitotane with cisplatin, etoposide and
doxorubicin.
• Recurrence is treated by debulking and chemotherapy.
11. PROGNOSTIC FACTOR
• Tumour size > 12 cm
• High mitotic activity > 6 mitoses/ high power field
• Intratumour haemorrhage
• McFARLANE STAGING –
Stage I and II, 5 year survival is 25%
Stage III and IV, 5-year survival is 5%.
13. CLINICAL FEATURES
• Centripetal obesity,
• Moonface
• Fullness of supraclavicular pad of fat.
• Buffalo hump
• Proximal muscle wasting.
• “Lemon on toothstick appearance”.
• Easy bruising
• Abdominal striae
14. DIAGNOSIS
• Loss of normal diurnal of serum cortisol. Values more than 4 fold the
upper limit of normal serum cortisol level is diagnostic.
• 24 hour urinary free cortisol is elevated > 90%.
• Low dose dexamethasone suppression test: 1 mg of dexamethasone is
injected
Normal— <1.8 mcg/ dl
Cushings—high >10 mcg/dl.
• Late night salivary cortisol—Cortisol concentration in saliva correlates
with free plasma cortisol.
15. • Measurement of corticotropin (ACTH):-
Low—corticotropin independent Cushing’s syndrome
High—corticotropin dependent Cushing’s disease
• Inferior petrosal sinus sampling of blood for ACTH shows central to
peripheral ratio of ACTH >3 in pituitary incidentaloma.
• Localising methods/imaging:
a) Adrenal—CT scan/MRI abdomen.
b) Pituitary—MRI pituitary
16. TREATMENT
A. MEDICAL MANAGEMENT
Metapyrone, ketoconazole, aminoglutethamide, mitotane.
B. SURGICAL MANAGEMENT
Pituitary disease
• Trans-sphenoidal microsurgery.
• Pituitary irradiation—conventional fractionated therapy.
• Sterotactic radiosurgery.
• Bilateral adrenalectomy.
Adrenal disease
• Unilateral adrenalectomy in adenoma, carcinoma.
• Bilateral adrenalectomy in macronodular adrenal hyperplasia and primary pigmented nodular
adrenal disease.
17. CONN’S SYNDROME
• It is primary hyperaldosteronism with excessive secretion of
aldosterone from the adrenal gland associated with suppression of
plasma renin activity.
CAUSES
• Aldosterone producing adrenocortical adenoma (Aldosteronoma)—
65%
• Idiopathic hyperaldosteronism—30%.
18. FEATURES
• Hypertension & hypokalaemia.
• Hypernatremia or normal sodium, metabolic alkalosis.
• In primary hyperaldosteronism—hypertension of early onset which is
difficult to control and is with hypokalaemia.
DIAGNOSIS:-
• Hypokalemia
• Increase in urinary potassium excretion.
• Elevated plasma aldosterone concentration (PAC) & suppressed
plasma renin activity (PRA),PAC: PRA > 30
19. LOCALISING TESTS:-
• CECT abdomen
• Selective adrenal venous sampling—Gold standard to differentiate
between unilateral versus bilateral aldosterone hypersecretion.
TREATMENT
• Adenoma—unilateral adrenalectomy.
• Idiopathic hyperaldosteronism—medical treatment with
spiranolactone.
20. VIRILISING SYNDROME OR ADRENOGENITAL
SYNDROME
• In female:
Virilism,
Ambiguous external genitalia,
Clitoral enlargement.
• In male:
Precocious puberty,
Premature fusion of epiphysis
Short stature.
21. CONGENITAL ADRENAL HYPERPLASIA
(ADRENOGENITAL SYNDROME)
• Due to enzyme 21 hydroxylase deficiency
• Autosomal recessive.
Treatment
1. Replacement of deficient steroids.
2. Genital manifestations of excess androgen production, particularly
in women require specialised surgery.
22. NEUROBLASTOMA
• Commonest childhood abdominal tumour.
• It is a tumour of adrenal medulla.
• An aggressive malignant tumour in childhood usually below the age
of 5 years.
• Incidence is equal in both sexes.
• It can cause distant spread to liver, bones (skull), orbit.
• It can occur anywhere in sympathetic chain but common in adrenal
gland (40%)
23. TYPES
1. PEPPER TYPE:- Right side adrenal
neuroblastoma with liver
secondaries. Common in infants.
2. HUTCHINSON’S TYPE:- Left side
adrenal neuroblastoma with
secondaries in orbit and skull.
Common in late childhood.
24. PATHOLOGY
• Gross - Tumour with vascularity,
necrosis, haemorrhage and often
calcifications.
• Histologically- contains uniform round
cells with Homer-Wright rosettes. PAS
stain is negative and NSE stain is
positive.
• Shimada’s histological classification:
1. Stroma rich tumour: Presence of
Schwannian spindle cell stroma.
2. Stroma poor tumour: Absence of
Schwannian spindle cell stroma.
25. CLINICAL FEATURES
• Huge mass per abdomen, in the loin which is non-mobile, not moving
with respiration. Knobby (nodular) surface, crosses the midline.
• Dancing eye syndrome and opsomyoclonus.
• Racoon’s eye sign is infraorbital ecchymosis due to secondaries in
retroorbital region
• Hypertension, fever, weight loss, anaemia, flushing (due to
catecholamine release) and sweating.
• Diarrhoea, hypokalaemia due to release of Vasoactive Intestinal
Polypeptide (VIP).
26. STAGING
• Stage I: Localised tumour with gross complete excision. Same side representative
nodes are negative on microscopy.
• Stage II A: Localised tumour with incomplete gross excision. Same side
representative nodes are negative on microscopy
• Stage II B: Localised tumour with or without complete gross excision. Same side
non adherent representative nodes are positive but contralateral nodes are (may
be enlarged) negative on microscopy
• Stage III: Unresectable unilateral tumour infiltrating across midline/ localised
tumour with opposite side node spread/bilateral nodal spread/midline tumour
with bilateral infiltration
• Stage IV: Any primary tumour with spread to distant nodes, bone, bone marrow,
liver, skin and other organs
• Stage IV S: Localised primary tumour (stage I, IIA, IIB) with spread to skin, liver or
bone marrow—limited to infants younger than one year
27. RISK GROUPS
• LOW RISK GROUPS:-
Stage I disease
Stage II disease with single N myc value
Stage II with favourable Shimada histology.
• INTERMEDIATE RISK GROUPS:-
Stage III without N myc amplification
Stage III with favourable Shimada’s histology.
• HIGH-RISK GROUPS:-
All patients with N myc amplification
Stage IV neuroblastoma
28. DIAGNOSIS
• Ultrasound, CT to assess the mass and secondaries in liver. MRI is
better than CT.
• Plain X-ray abdomen shows stippled calcification.
• Urinary VMA and Homovanillic acid (HVA) estimation in 90% cases.
• MIBG scan.
• Bone marrow biopsy may be positive in 60% cases. Iliac bone both
sides under GA.
• PET scan is done if MIBG is not beneficial.
29. TREATMENT
• Adrenalectomy (Complete surgical excision).
• In inoperable cases, debulking is beneficial.
• Postsurgical radiotherapy and folic acid supplements are useful.
• Adjuvant Chemotherapy with carboplatin, doxorubicin,
cyclophosphamide and etoposide.
• Rarely spontaneous regression of tumour is known to occur.
30. • Low risk groups are treated by surgery.
• Intermediate risk groups are treated by surgery and multidrug
chemotherapy.
• High risk groups are treated by high dose multidrug chemotherapy and
later surgery.
Other treatment modalities—
• Retinoids (Fenretinide),
• Immunotherapy (GD2),
• Radionuclide targeted therapy,
• Tyrosine kinase/aurora kinase inhibitors
• Bone marrow or stem cell transplantation are newer methods used
31. PROGNOSIS
Factors are :-
Age of the child.
Stage of the disease.
Shimada’s histology.
N myc amplification status.
Survival rate
Low risk has got 3 years survival—90%
Intermediate risk—70%
High risk group - 30%.
32. PHAEOCHROMOCYTOMA
• It is a tumour arising from chromaffin cells, commonly from the
adrenal medulla but occasionally can arise from extraadrenal
chromaffin tissues (Organ of Zuckerkandl)
• It is catecholamine secreting tumours that arise from chromaffin cells
of sympathetic origin derived from neural crest representing a
potentially curable form of hypertension.
• Incidence is 0.005–0.1% of general population
• It mainly secretes noradrenaline or other catecholamines.
33. RULE OF 10s
Tumour is:
• 10% malignant
• 10% extra-adrenal
• 10% bilateral
• 10% familial
• 10% childhood
• 10% multiple
• 10% not associated with hypertension
• 10% calcified
34. EXTRA-ADRENAL PHEOCHROMOCYTOMA
• 10% common
• Occurs in organ of Zuckerkandl, urinary bladder, paravertebral or
para-aortic area, thorax, neck.
• It secretes norepinephrine rather than epinephrine because they lack
the enzyme PNMT.
35. CLINICAL FEATURES
• Commonest presentation is severe headache.
• Palpitation, dyspnoea, weakness, pallor, blurred vision and other
symptoms of sympathetic over activity.
• They may present as persistent or paroxysmal hypertension (90%).
• As an abdominal mass which is nonmobile, smooth, does not move
with respiration, crossing the midline, palpation may cause
fluctuation in BP.
• It may precipitate hypertensive encephalopathy, cardiac arrhythmias
or cerebral haemorrhage.
• Panic attacks and sudden death are known to occur.
36. Phaeochromcytoma is associated with
• MEN-IIa or MEN-IIb syndromes
• Familial multiple neurofibromatosis (von Recklinghausen’s disease)
• Von Hippel-Lindau syndrome (cystic lesion of pancreas, non-
functioning islet cell tumour, phaeochromocytoma),
• RCC, CNS and retinal haemangioblastoma.
Familial paraganglioma syndrome may be an association with carotid
body and extra-adrenal paraganglioma.
37. INVESTIGATIONS
• VMA excretion in urine in 24 hours will be >7 mg/24 hr in
pheochromocytoma.
• Ultrasound abdomen, IVU, CT scan.
• MRI is preferred to CT as contrast used for CT scan can precipitate paroxysms.
• Measurement of plasma-free metanephrines is the recommended test of
choice for excluding or confirming diagnosis of phaeochromocytoma.
• Urinary nor metadrenaline or other catecholamines estimation.
• Iodine labelled metaiodo-benzylguanidine (I, MIBG). MIBG is useful to find out
extra-adrenal involvement.
• Measurement of plasma free metanephrine and normetanephrine has the
highest sensitivity and specificity and appears to be the best initial test for
screening patients with pheochromocytoma.
38. TREATMENT
ADRENALECTOMY
Before surgery, BP is controlled initially by α-blocking agent,
phenoxybenzamine or doxazosin; then by β-blocking agent propranolol.
Then during surgery, sodium nitroprusside IV infusion is used.
• Adequate fluid therapy to have volume expansion is essential.
• Intraoperative hypovolemia and postoperative hypotension should be
controlled.
• Handling of adrenal tumour on table must be careful and gentle.
• Adrenal vein should be ligated first.
• CVP, arterial lines should be present for monitoring.
• Rupture and spillage of tumour should be prevented.
39. MALIGNANT PHEOCHROMOCYTOMA
• It is 10% common.
• It is more common in extra-adrenal site.
• It commonly spreads to lymph nodes, bone and liver.
• Adrenalectomy in early tumour and debulking in advanced cases with
α-blockers, mitotane and I131 MIBG therapy and combination
chemotherapy are the therapeutic choices.
• Overall prognosis is not good with 5-year survival being <50%.
