1. Pheochromocytomas are rare tumors that originate from chromaffin cells in the adrenal medulla or extra-adrenal paraganglia. They secrete catecholamines and can cause hypertension. 2. Neuroblastoma is a common malignant tumor in children under 5 years old that originates from embryonic nerve cells, often in the adrenal medulla or chest. It commonly metastasizes and presents with abdominal issues or carcinoid syndrome. 3. Ganglioneuroma is a rare, benign tumor of the sympathetic nervous system in adults that produces symptoms due to its size and location. It is diagnosed using imaging and urine tests. Surgery is usually sufficient treatment.

1. FRONT E
I R
Lecture 9. Adrenal
Medulla Diseases:

2. Pheochromocytoma:
• Pheochromocytomas are neoplasms composed of
chromaffin cells, which, like their nonneoplastic
counterparts, synthesize and release catecholamines
and, in some cases, other peptide hormones.
• They are uncommon.
• Pheochromocytomas usually subscribe to a convenient
“rule of 10s”:
• 10% of pheochromocytomas are extraadrenal,
occurring in sites such as the organ of Zuckerkandl and
the carotid body, where they usually are called
paragangliomas, rather than pheochromocytomas.

3. • 10% of adrenal pheochromocytomas are bilateral;
this proportion may rise to 50% in cases that are
associated with familial syndromes.
• 10% of adrenal pheochromocytomas are
malignant, although the associated hypertension
represents a serious and potentially lethal
complication of even benign tumors.
• 10% of adrenal pheochromocytomas are not
associated with hypertension. Of the 90% that
present with hypertension, approximately two-
thirds have “paroxysmal” episodes associated with
sudden rise in blood pressure and palpitations,
which can, on occasion, be fatal.

5. •Pathogenesis:
• 25% of individuals with pheochromocytomas and
paragangliomas harbor a germ line mutation in
one of at least six known genes.
• RET, which causes type 2 MEN syndromes.
• NF1, which causes type 1 neurofibromatosis.
• VHL, which causes von Hippel-Lindau disease.
• Three genes encoding subunits within the succinate
dehydrogenase complex (SDHB, SDHC, and SDHD),
which is involved in mitochondrial electron
transport and oxygen sensing.
• It is postulated that loss of function in one or more
of these subunits leads to stabilization of the
transcription factor hypoxia-inducible factor 1α
(HIF-1α), promoting tumorigenesis.

6. • Morphology:
• Varying size.
• Hemorrhagic masses.
• On cut surface:
• Smaller pheochromocytomas _ are yellow-tan,
well-defined lesions.
• Larger pheochromocytomas _ are hemorrhagic,
necrotic, and cystic.
• On microscopic examination:
• Pheochromocytomas are polygonal to spindle-
shaped chromaffin cells and their supporting cells.

9. • Clinical feature:
1. Hypertension, tachycardia, palpitations.
2. Headache.
3. Sweating.
4. Tremor.
5. Sense of apprehension.
6. Abdominal or chest pain.
7. Nausea, and vomiting.

10. • Diagnosis:
• Vanillylmandelic acid and metanephrines in the
urine and are end product of catecholamines.
• Treatment:
• Small lesion require surgical excision.
• Large with multi focal lesion require long-term
medical treatment for hypertension.
• Phenoxybenzamine ‘nonselective, irreversible
antagonist of the alpha-adrenergic receptors class
of drugs’.
• β-Blocker.
• Metyrosine (catecholamine synthesis inhibitor).

11. Neuroblastoma:
• also called as sympathicoblastoma.
• Is a common malignant tumour of embryonic nerve
cells.
• Most often occurs in children <5 years old.
• Primarily located in the adrenal medulla.
• Occasionally located in the posterior mediastinum
(paraspinal).
• Commonly metastasize to skin and bones.

14. • Clinical feature:
1. Abdominal distension.
2. Fever.
3. Weight loss.
4. Malaise.
5. Carcinoid-like syndrome = watery diarrhoea,
flushing of the skin and hypokalaemia all these
probably due to production of kinins or
prostaglandins by the tumour.
• Diagnosis:
• Foci of calcification observed on radiologic
examination of the abdomen.
• 24-hour urine detection of vanillyl mandelic
acid (VMA) and homovanillic acid (HVA).

15. • Treatment:
• Neuroblastoma Surgery.
• Chemotherapy for Neuroblastoma.
• Radiation Therapy for Neuroblastoma.
• High-dose Chemotherapy and Stem Cell Transplant for
Neuroblastoma.
• Retinoid Therapy for Neuroblastoma.
• Immunotherapy for Neuroblastoma.
Prognosis depends on age.
• Children <1 year old have a
good prognosis

16. Ganglioneuroma:
• A ganglioneuroma is a mature, benign and
uncommon tumour occurring in adults.
• It is derived from ganglion cells, most often in the
posterior mediastinum, and uncommonly in other
peripheral ganglia and brain.
• The tumour produces symptoms because of its size
and location.
• Catecholamines and their metabolites can be
detected in large amounts in the 24-hour urine
specimen of patients with ganglioneuroma.

18. • Diagnosis:
• Magnetic resonance imaging (MRI) and computed
tomography (CT) for evaluating the extension of
spinal tumors.

19. • Treatment:
• Surgery alone.
• However, ganglioneuroblastoma intermixed (GNBI)
is widely seen as a malignant entity and –
depending on stage – treated with multimodal
therapy.