Carcinoid Syndrome

Midgut carcinoids are argentaffin-positive and have a high serotonin content. They most frequently cause the typical carcinoid syndrome when they metastasize.

Reference:
Harrisons Principles of Internal Medicine, 18th Edition, Page 3058

Diarrhea is present in 68–84% at some time in the disease course. Diarrhea usually occurs with flushing. Steatorrhea is present in 67%. So steatorrhea is not a rare manifestation.
Rare manifestations of Carcinoid syndrome includes retroperitoneal fibrosis causing urethral obstruction, Peyronie’s disease of the penis, intraabdominal fibrosis, and occlusion of the mesenteric arteries or veins.

Reference:
Harrisons Principles of Internal Medicine, 18th Edition, Page 3062

The cardiac disease is due to the formation of fibrotic plaques involving the endocardium. The dense fibrous deposits are most commonly on the ventricular aspect of the tricuspid valve and less commonly on the pulmonary valve cusps. Overall, in patients with carcinoid heart disease, 97% have tricuspid insufficiency, 59% tricuspid stenosis, 50% pulmonary insufficiency, 25% pulmonary stenosis, and 11% left-side lesions. 80% of patients with cardiac lesions develop heart failure. Lesions on the left side are much less extensive and most frequently affect the mitral valve.

Serotonin does not appear to be involved in the flushing because flushing is not relieved by serotonin receptor antagonists.

Flushing associated with it affects predominantly upper part of the body especially the neck and face.

In patients with carcinoid heart disease, 97% have tricuspid insufficiency, 59% tricuspid stenosis, 50% pulmonary insufficiency, 25% pulmonary stenosis, and 11% (0–25%) left-side lesions.

Midgut carcinoids account for 60–67% of cases of carcinoid syndrome, foregut tumors for 2–33%, hindgut for 1–8%, and an unknown primary location for 2–15%.

Ref: Harrisons principles of internal medicine, 18th edition, Page: 3063.

Ans. is ‘b’ i.e., Constipation

Answer is A (Pulmonary valve)

Carcinoid syndrome most frequently involves the ventricular aspect of the tricuspid valve.

Cardiac manifestations of carcinoid syndrome

• Cardiac disease is due to involvement of endocardium by dense fibrous deposits
• Cardiac disease primarily involves the right side (although left side lesions may also occur)
• The most commonly involved valve is tricuspid valve (ventricular surface/under surface)
• The second most commonly involved valve is pulmonary valve
• Predominant vavular lesion due to involvement of tricuspid valve is tricuspid regurgitation (valve is fixed open)
• Predominant valvular lesion due to involvement of pulmonary valve is pulmonic stenosis (valve is constricted)
• Most patients with cardiac lesion develop heart failure (80%)

Answer is B (Tricuspid Regurgitation)

Carcinoid syndrome most frequently involves the ventricular aspect of the tricuspid valve and leads to Tricuspid Regurgitation

Answer is B (Inflow tract of RV)

The most commonly involved valve in^, carcinoid syndrome is tricuspid valve which forms the inflow tract of Right ventricle.

Most commonly involved part of heart : Inflow tract of RV (Tricuspid valve) Second most commonly involved part of heart : Outflow tract of RV (Pulmonic valve)

Answer is C (Metastasis to bone is common in Midgut Carcinoids):

Palliative Care (Oxford University Press, 2009)/ 452; Multiple references

Metastasis to bone is rare in Midgut Carcinoids and is Common in Foregut Carcinoids.

Ans.D. Foregut carcinoids are usually argentaffin positive.

Foregut tumors (carcinoids) have low serotonin levels and are argentaffin negative.

Carcinoid Syndrome

Typical Carcinoid Syndrome

• Elevated levels of plasma serotonin.
• Elevated levels of urinary 5-HIAA.

Atypical Carcinoid Syndrome-

• Plasma serotonin levels are normal.
• Plasma and urinary levels of 5HTP are increased (Urinary 5HIAA may he normal or mildly elevated).

Typical carcinoid syndrome is charachteristic of Midgut carcinoids.

Midgut Carcinoids: Typical Carcinoid Syndrome-

• Midgut tumors have high serotonin content are Argentaffin positives.
• Most frequently cause a ‘typical’ carcinoid syndrome when they metastize.
• Release serotonin and tachykinins (neuropeptide K. substance K, substances P).
• Rarely secrete 5HTP or ACTH.
• Metastatis to bone is uncommon (less common).

Atypical carcinoid syndrome is charachteristic of foregut carcinoids.

Foregut Carcinoids: Atypical Carcinoid Syndrome-

• Foregut tumor have low serotonin content, are argentaffin negative but argyrophillic Q.

• Usually do not produce carcinoid syndrome but when they produce a carcinoid syndrome it is charachtristically usually an Atypical carcinoid syndrome.

Occasionally secrete ACTH or 5HTP-

• May metastize to bone.
• Are often multihormonal.

Answer is D (VMA):

5HIAA, 5HT, 5HTP are metabolites of Trvptophan / Serotonin that may be elevated in carcinoid tumors.

Vanillvl mandilic acid (VMA) is the principal metabolite of catecholamines secreted by adrenal medulla. Elevated VMA levels in urine is a feature of increased catecholamine secreting tumors, typically pheochromocytomas (and not carcinoid tumors).

Answer is B (Tricuspid valve);

The most common site of involvement is the – Ventricular surface of Tricuspid valve.

‘Cardiac manifestations in carcinoid syndrome are due to fibrosis involving the endocardium, primarily on the right side although left side lesions also occur. Dense fibrous deposits are most commonly on the ventricular aspect of the tricuspid valve and less commonly on the pulmonary valve cusps.’

They can result in either constriction of valves (stenosis) or fixation of valves in open (regurgitation)

–  Abnormality produced due to tricuspid valve involvement – Tricuspid regurgitation Q

– Abnormality produced due to pulmonary valve involvement – Pulmonary stenosis Q

Ans. C i.e. Serotonin

Carcinoid syndrome

• It refers to the array of symptoms that occur secondary to carcinoid tumors.
• The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction.
• It is caused by the endogenous secretion of mainly serotonin and kallikrein.

Ans. C: Acute appendicitis

Striking skin color changes may occur, ranging from pallor or erythema to a violaceous hue.

Abdominal cramps with recurrent diarrhea occur and are often the patient’s major complaint. Malabsorption syndrome may occur. Patients with valvular lesions may have a heart murmur. A few patients have asthmatic wheezing, and some have decreased libido and erectile dysfunction; pellagra develops rarely.

Ans. D

• Carcinoid syndrome develops in some people with carcinoid tumors and is characterized by cutaneous flushing, abdominal cramps, and diarrhea.
• Carcinoid tumors occur throughout the gastrointestinal tract, most commonly in the appendix, ileum, and rectum in decreasing order of frequency.
• Carcinoid syndrome consists of the following features-

a) Carcinoid tumor is malignant

b) Secondaries in the liver

c) Symptoms are- red- blue cyanosis of the skin, flushing and asthmatic attacks, intestinal hyperperistalsis causing diarrhea, pulmonary and tricuspid stenosis with CCF.

• Right-sided valvular heart disease may develop after several years.
• The syndrome results from vasoactive substances (including serotonin, bradykinin, histamine, prostaglandins, polypeptide hormones) secreted by the tumor, which is typically a metastatic intestinal carcinoid.
• Diagnosis is clinical and by demonstrating increased urinary 5-hydroxy indole acetic acid.
• Tumor localization may require a radionuclide scan or laparotomy.
• Treatment of symptoms is with somatostatin or octreotide, but surgical removal is performed where possible; chemotherapy may be used for malignant tumors.