UBP 5.3 (Short Form): Endocrine – Carcinoid Syndrome

Question 1

You ask a few questions, and find that her “bad hot-flashes” began to bother her about the same time that she began having problems with diarrhea. What do you think may be happening?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 1

At her age, this could very well be a symptom of menopause.

However, the fact that she is also experiencing chronic diarrhea and has a heart murmur consistent with tricuspid regurgitation, would suggest that her “hot flashes” may be the cutaneous flushing associated with carcinoid syndrome.

The constellation of diarrhea, flushing, and cardiac involvement (i.e. pulmonic stenosis or tricuspid regurgitation) is referred to as the carcinoid triad.

If time allowed, this could be further investigated by measuring urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA).

Question 2

The surgeon tells you that he suspects a small bowel obstruction secondary to carcinoid tumor. What is carcinoid syndrome?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 2

Carcinoid syndrome is the term applied to the complex signs and symptoms that results when a carcinoid tumor releases excessive amounts of circulating hormones, such as – histamine, bradykinin, tachykinin, and serotonin, into systemic circulation.

In the case of non-intestinal tumors (i.e. head and neck, lungs, and breast) or gastrointestinal tumors that have metastasized to the liver, these substances bypass the portal circulation and result in – a variety of symptoms including –

• cutaneous flushing of the upper body
  
  • (bradykinin and/or histamine),
• bronchoconstriction
  
  • (bradykinin, histamine, and/or serotonin),
• diarrhea (serotonin),
• right-sided heart disease
  
  • (possibly secondary to serotonin and/or tachykinin),
• hypotension
  
  • (bradykinin and/or serotonin), and
• hypertension
  
  • (serotonin).

Question 3

How is carcinoid syndrome diagnosed?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 3

When symptomatology suggests the possibility of carcinoid syndrome, the diagnosis can be confirmed by measuring the 24-hour urine levels of 5-hydroxyindoleacetic acid, a breakdown product of serotonin.

• Imaging techniques*, such as – octreoscan (scintigraphy), PET/CT scan, CT scan, or MRI are often used to localize both primary and metastatic lesions.
• Elevated serum levels of chromogranin A*, a glycoprotein secreted by carcinoid tumors, are also consistent with carcinoid tumor secretion.

Question 4

Why don’t all patients with carcinoid tumors develop carcinoid syndrome?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 4

Most carcinoid tumors are located in the gastrointestinal tract, where released vasoactive substances enter the portal circulation and are removed by the liver prior to entering the systemic circulation.

Carcinoid syndrome develops only when these substances bypass the portal system, as is the case with tumors that have metastasized to the liver, or are located outside of the gastrointestinal tract (pulmonary, ovarian, etc.).

Question 5

What do you think of her heart murmur? What is the likely cause?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 5

This heart murmur is consistent with tricuspid regurgitation,

the most common cardiac finding associated with carcinoid syndrome

(tricuspid stenosis, pulmonic regurgitation, and pulmonic stenosis occur less commonly).

Serotonin-induced fibrosis can lead to ⇒

• valvulopathy (tricuspid and/or pulmonary valve stenosis or regurgitation),
• pulmonary hypertension, and
• right-sided heart failure.

The left side of the heart is protected by the pulmonary degradation of serotonin, except in the case of pulmonary metastasis or right-to-left intracardiac shunt.

Her heart murmur, combined with hepatomegaly, would raise concerns about significant right-heart dysfunction, prompting appropriate monitoring and further pre-operative evaluation, including an echocardiogram.

Question 6

What would you do, preoperatively, to reduce the risk of carcinoid crisis?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 6

The two most effective steps I would take in the preoperative period to reduce the risk of carcinoid crisis would be to:

1. ensure the perioperative administration of a somatostatin analogue, such as octreotide, to reduce tumor secretion of serotonin
   
   • (if possible, a somatostatin analogue, such as octreotide, should be started 2 days before surgery and continued throughout the perioperative period – some sources say begin administration up to 2 weeks prior to surgery and continue for a week postoperatively); and
2. optimize the patient’s intravascular fluid volume, which could be significantly depleted in this patient with diarrhea, vomiting, and bowel obstruction.

Additionally, I would consider administering:

1. an anxiolytic, to prevent the stress-induced release of vasoactive substances from the carcinoid tumor;
2. H1- and H2-blockers, to attenuate the effects of histamine, such as vasodilation, flushing, and bronchoconstriction (some carcinoid tumors release histamine);
3. alpha- and Beta-adrenergic receptor blockers, to prevent the catecholamine-mediated release of vasoactive substances from the tumor; and/or
4. steroids, which may be beneficial due to inhibition of the kallikrein cascade.

Question 7

What additional steps would you take to prepare this patient for surgery?

(A 5’3”, 78 kg, 47-year-old female is scheduled for laparoscopy after presenting to the emergency room with nausea, vomiting, fever, and abdominal pain. She says her medical history is significant for asthma, 30 years of tobacco use, and pseudotumor cerebri, for which she has a ventriculoperitoneal shunt. She also adds that, for the past several months, she has been experiencing chronic diarrhea and occasional “bad hot-flashes”. On exam, a 3/6 pansystolic heart murmur, best heard at the left sternal border, is noted along with hepatomegaly. She has never had surgery and says penicillin gives her a rash. VS: HR = 88, BP = 108/64, R = 12, T = 36.8°C)

Answer 7

Considering that this patient with carcinoid tumor, small bowel obstruction, asthma, a ventriculoperitoneal shunt, and a history of tobacco use is undergoing laparoscopy,

there are a number of additional steps I would take to prepare her for surgery, including:

1. decompressing her stomach and/or small intestine with a gastric or intestinal tube, to reduce the risk of aspiration
   
   • (bowel obstruction may result in the accumulation of significant amounts of gastric fluid);
2. correcting any electrolyte disturbances
   
   • (i.e. hyponatremia, hypochloremia, hypokalemia),
   • resulting from hypovolemia or the loss of gastric and/or intestinal fluid
   • (bowel obstruction leads to vomiting and third-spacing of fluids,
   • while carcinoid syndrome can cause diarrhea);
3. identifying and treating any acid base disturbances,
   
   • resulting from dehydration and/or the loss of acidic or alkaline secretions
   • (Most commonly, bowel obstruction leads to dehydration and the loss of alkaline secretions, with subsequent metabolic acidosis;
   • carcinoid-induced diarrhea would be contributory.
   • However, the significant loss of acidic gastric fluid that occurs with vomiting could lead to metabolic alkalosis.);
4. restoring fluid losses that have occurred secondary to vomiting, diarrhea, nasogastric suctioning (gastric decompression), and fluid-sequestration into the bowel and peritoneal cavity
   
   • (bowel obstruction can result in the loss of > 10 L of fluid per day);
5. evaluating and optimizing her pulmonary status
   
   • (history of asthma and long term tobacco use),
   • but taking a careful history,
   • examining the patient,
   • ordering pulmonary function tests if indicated, and
   • providing a B2-agonist
     
     • (keep in mind that this patient’s asthma increases her susceptibility to serotonin and/or histamine-induced bronchospasm);
6. providing aspiration prophylaxis
   
   • (high risk of aspiration due to small bowel obstruction, nausea, and vomiting),
   • recognizing that the large volume of sequestered fluid in the stomach may reduce the effectiveness of nonparticulate antacids and H2-blockers, and
   • that metoclopramide should be avoided in the setting of suspected bowel obstruction;
7. administering ondansetron to address the increased risk of postoperative nausea and vomiting associated with laparoscopic surgery
   
   • (given her carcinoid syndrome, it makes sense to give a serotonin antagonist for nausea prophylaxis); and
8. consulting her neurosurgeon to –
   
   • discuss the ventriculoperitoneal shunt’s functionality,
   • intraoperative intracranial pressure monitoring requirements
     
     • (intracranial pressures may increase during laparoscopy due to shunt dysfunction during pneumoperitoneum formation, shunt occlusion by soft tissue, retrograde diffusion of carbon dioxide through the distal end of the catheter, increased systemic vascular resistance, increased PaCO2, and, when utilized, Trendelenburg positioning), and
   • potential measures to reduce the risk of increased intracranial pressures
     
     • (i.e. low insufflation pressures, externalizing the shunt, and clamping the distal end of the shunt before surgery).