Disorders of Adrenal Medulla & Carcinoid Tumor and Syndrome - Free MCQ

Paraganglioma refers to tumours that produce catecholamines, located in the skull base and neck. The traditional rule of tens applies to pheochromocytoma (see page 2740, Harrison 20th edition).

• The organ of Zuckerkandl consists of a cluster of chromaffin cells found near the beginning of the inferior mesenteric artery or close to the aortic bifurcation.
• This site is the most prevalent extra-adrenal location for pheochromocytoma.

Urinary VMA is employed for diagnosing neuroblastoma, not pheochromocytoma. The most accurate test for pheochromocytoma is urinary fractionated metanephrine.

Vanillyl mandelic acid is a metabolic by-product of norepinephrine and epinephrine. It is employed in the identification of tumours originating from the neural crest:

• Neuroblastoma
• Pheochromocytoma
• Ganglioblastoma
• Ganglioneuroma
• Severe anxiety

For the diagnosis of pheochromocytoma, measuring fractionated metanephrine levels in urine and stool is recommended.

Preparing patients for surgery is crucial for ensuring safety. Alpha-adrenergic blockers, such as phenoxybenzamine, should be started at low doses, for instance:

• 5-10 mg orally three times daily

Doses can be gradually increased as tolerated over a few days. Typically, sufficient alpha blockade is achieved after:

• 7 days

The usual final dosage is:

• 20-30 mg of phenoxybenzamine three times daily

This is a straightforward logical query regarding the insertion of a needle into a tumour located deep within the medulla. This procedure generates catecholamines, akin to a volcano poised to erupt.
Tests for pheochromocytoma include:

• Screening test: 24-hour urinary fractionated metanephrine levels
• Initial operative choice (IOC): plasma total free metanephrine test
• M.I.B.G. scan is conducted to determine whether the tumour is adrenal or extra-adrenal (situated at the organ of Zuckerlandt)

Phaeochromocytoma generates norepinephrine in 80% of cases, resulting in hypertension. However, because catecholamines are released in short bursts, blood pressure (BP) rises for several hours each day, a condition known as episodic hypertension. Over time, this excess of catecholamines leads to ongoing vasoconstriction, termed a volume contracted state. This phenomenon accounts for both postural hypotension and the relative increase in packed cell volume observed in the patient.

• Typical symptoms include episodes of palpitations, headaches, and profuse sweating, which together form a classic triad.
• The presence of all three symptoms alongside hypertension suggests a likely diagnosis of pheochromocytoma.

Nonetheless, pheochromocytomas can remain asymptomatic for years, with some tumours reaching a significant size before symptoms become noticeable. Hypercalcaemia is also associated with pheochromocytoma. The parathyroid hormone-like peptide extracted from the tumour accounts for the hypercalcaemia.

• The term paraganglioma refers to catecholamine-producing tumours located in the head and neck.
• These tumours may produce minimal or no catecholamines at all.

About 25-33% of individuals with a pheochromocytoma or paraganglioma possess an inherited syndrome. Neurofibromatosis type 1 (NF 1) was the initial syndrome linked to pheochromocytomas. The NF1 gene acts as a tumour suppressor by modulating the Ras signalling pathway. Classic characteristics of neurofibromatosis encompass:

• multiple neurofibromas
• cafe au lait spots
• axillary freckling of the skin
• Lisch nodules of the iris

Pheochromocytomas are present in only about 1% of these patients and are primarily found in the adrenal glands.

Due to heightened sympathomimetic activity, phaeochromocytoma results in weight reduction. Phaeochromocytoma generates norepinephrine in approximately 80% of cases, resulting in hypertension. However, as catecholamines are released in brief bursts and act for a limited time, blood pressure rises for several hours each day, a condition known as episodic hypertension. This excess of catecholamines will ultimately cause persistent vasoconstriction, termed a volume-contracted state. This phenomenon accounts for postural hypotension.

The initial treatment for scintigraphically confirmed metastasis involves I-M.I.B.G administered in doses of 100-300 mci over a span of 3 - 6 cycles. Averbuch's chemotherapy regimen consists of:

• dacarba­zine (600 mg/m² on days 1 and 2),
• cyclophosphamide (750 mg/m² on day 1),
• vincristine (1.4 mg/m² on day 1),

This protocol is repeated every 21 days for a total of three to six cycles.

Beta blockers will result in unopposed alpha activity, which exacerbates pre-existing vasoconstriction in phaeochromocytoma. Therefore, the appropriate approach to managing patients with phaeochromocytoma is to first initiate alpha blockade, followed by beta blockade.

• Metyrosine prevents catecholamine production and is effective in cases of malignant phaeochromocytoma.
• An adequate alpha blockade generally requires a period of 7 days.
• The typical final dosage is 20-30 mg of phenoxybenzamine taken three times daily.
• A hypertensive crisis may necessitate sodium nitroprusside.
• Oral prazosin or intravenous phentolamine can be utilised to manage paroxysms while waiting for sufficient alpha blockade.

Before surgery, blood pressure must consistently remain below 160/90 mmHg, with moderate orthostasis. After initiating alpha blockers, beta blockers (for instance, 10 mg propranolol three to four times daily) may be introduced and increased as required if tachycardia continues. Other antihypertensives, including calcium channel blockers or angiotensin-converting enzyme inhibitors, have been employed when blood pressure is challenging to control with phenoxy-benzamine alone.

5-HIAA is the primary urinary metabolite of serotonin, a widely occurring bioactive amine.

• Most carcinoid tumours generate serotonin, and thus 5-HIAA, in large quantities.
• This is particularly true for those that cause the carcinoid syndrome, which includes symptoms such as flushing, hepatomegaly, diarrhoea, bronchospasm, and heart disease.

Argentaffin cells found in carcinoid tumours generate SHT derivatives, such as serotonin. Chromaffin cells, observed in phaeochromocytoma, produce epinephrine and norepinephrine.

Enterochromaffin (EC) cells, known as 'Kulchitsky cells', are a specific type of enteroendocrine and neuroendocrine cell found within the epithelial lining of the digestive and respiratory tracts, which release serotonin. Lung NETs are categorised into four types:

• Typical carcinoid (also referred to as bronchial carcinoid tumour, Kulchitsky cell carcinoma I (KCC-I))
• Atypical carcinoid (also known as well-differentiated neuroendocrine carcinoma (KC-II))
• Intermediate small cell neuroendocrine carcinoma
• Small cell neuro-endocarcinoma

Carcinoid syndrome is linked to the formation of valvular defects on the right side of the heart. The mnemonic to remember is T.I.P.S = Tricuspid insufficiency and Pulmonic stenosis.

• Dense fibrous deposits are observed on the ventricular side of the Tricuspid valve
• These deposits are less frequently seen on the cusps of the pulmonary valve.

The prevalence of heart disease in carcinoid syndrome includes:

• Tricuspid insufficiency: 97%
• Tricuspid stenosis: 59%
• Pulmonary insufficiency: 50%
• Pulmonary stenosis: 25%
• Left side lesions: 11%

• If the primary tumour originates from the GI tract (thus releasing serotonin into the hepatic portal circulation), carcinoid syndrome typically does not manifest until the disease has progressed to a stage that exceeds the liver's capacity to metabolise the released serotonin.

• This condition leads to a heart that maintains a normal rhythm and contractility but experiences reduced preload and end-diastolic volume.