PHEOCHROMOCYTOMA

Definition

This is tumour of adrenal medulla, which is derived from chromaffin cells and which produce catecholamines

Aetiology

Prevalence of pheochromocytoma in patients with hypertension is 0.1-0.6%

In total 4% of incidentalomas are pheochromocytoma . Sporadic pheochromocytoma occurs after the fourth decade, hereditary forms are diagnosed earlier

Pheochromocytoma is known as 10% tumour as

10% tumours are inherited,10% are extra-adrenal,10% are malignant,10% are bilateral and 10% occur in children

Hereditary pheochromocytoma occur in several tumour syndromes

1.Multiple endocrine neoplasia type-2:an autosomal dominant inherited disorder that is caused by activating germline mutations of RET proto-oncogene.

2.Familial paraganglioma(PG) syndrome:Glomus tumour of the carotid body and extra-adrenal paraganglioma are characteristic in this syndrome,which is caused by succinate dehydrogenase complex-B(SDHB) and SDHD genes.

3.von Hippel –Lindau(VHL) syndrome:they have early onset of bilateral kidney tumours, pheochromocytoma,cerebellar and spinal hemangioblastomas and pancreatic tumours,they have a germline mutation in VHL gene

4.Neurofibromatosis(NF) type 1: pheochromocytoma in combination with fibromas on skin and mucosae(cafe-au-lait skin spots) are indicative of germ line mutation in the NF1 gene

Pathology

Pheochromocytomas are greyish-pink on the cut surface and are usually highly vascularised. Areas of haemorrhage and necrosis seen. Microscopically tumour cells are polygonal but can vary. The differentiation of malignant and benign is difficult,except if metastases are present.

            An increased PASS (Pheochromocytoma of Adrenal gland scale score) indicates malignancy as does a high number of Ki-67 positive cells, vascular invasion or a breached capsule

                Pheochromocytomas may also produce calcitonin, ACTH, vasoactive intestinal peptide(VIP) and parathyroid hormone related protein(PTHrP).In patients with MEN-2, the onset of Pheochromocytoma is preceded by adrenal medullary hyperplasia, usually bilateral, Pheochromocytoma is rarely malignant in MEN-2

Clinical Features

In total 90% of patients combination of headache, sweating and palpitation have a Pheochromocytoma.symptoms may be precipitated by physical training, general anaesthesia, drugs and agents(contrast media, tricyclic antidepressant, metoclopramide and opiates. some asymptomatic or with normal or intermittent hypertension. other symptoms are weight loss,pallor,hyperglycaemia,Nausea

Diagnosis

1.Determination of Adrenaline, Nor adrenaline, metanephrine and normetanephrine levels in a 24 hr urine collection(catecholamines exceed the normal range by 2-40 times)

2.Determination of plasma free meta and normetanephrine is highly sensitive

3.MRI is preferred more than CT scan(classically shows a “swiss cheese pattern”)

4.I-MIBI Single photon emission CT(SPECT) identify 90% tumours, extra adrenal tumours and metastases

Treatment

Laparoscopic resection

Tumour>8-10cm or radiological signs of malignancy an open approach should be considered

Preoperative

After biochemical diagnosis treat with alpha blocker(phenoxybenzamine) start with 20mg initially increase dose by 10 mg daily until a dose of 100-160 mg is reached

Beta blocker given after alpha blockage if arrhythmia and tachycardia is present

Intraoperative

Alfa blockage needed, fall in blood pressure occur when adrenal vein is ligated.

Postoperative complication -hypovolaemia ,hyperglycaemia.Life long follow up needed for recurrent and metastatic tumour