User:JackNagam/Carcinoid syndrome

Sheehan Syndrome Peer Review

In the signs and symptoms section, there are a lot of comparisons to other disease processes. While I understand that hypopituitarism would present with hormonal deficiencies of those syndromes, consider removing the compared syndrome and simply talking about the signs/symptoms associated. I feel this will make this section less medical jargon-y. Also there is a quote in the second paragraph. I am not sure if this was just impossible to paraphrase or just made more sense this way but you may want to try to think of removing this.

In the causes section, consider moving the small part of the first paragraph discussing physiologic pituitary growth to the pathophysiology section. I think it is hard to differentiate what should go where but discussing what specific cells grow more and why might be better suited for pathophysiology.

In the pathophysiology section, there is another quote which may be better taken out and paraphrased appropriately for wikipedia if possible. Just as an idea, an image of the vasculature supplying the pituitary may be good here since you discuss the blood supply a lot. I would consider moving the discussion of autoimmune causes to a research section.

In the treatment section, I feel that the statement regarding glucocorticoids needs a specific citation since it seems that it is discussing a little more than basic hormone replacement.

In the history section, there are a few sentences that need citations. I would assume they come from the same place as the rest of the section but they should be added at the end of each section.

Lastly, I know you had the problem of reference duplication so I took the liberty of manually fixing them. Hope it stays that way. Great job on the edits you've done.

Lead
Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to neuroendocrine tumors (formerly known as carcinoid tumors). The syndrome is caused by the release of biological factors from the tumors that circulate in the blood causing symptoms such as flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction.

Signs and Symptoms
The carcinoid syndrome occurs in approximately 10% of all neuroendocrine tumors or about 30-40% of more advanced/well developed neuroendocrine tumors. The biologically active substances that are released by the tumors cause the symptoms of the carcinoid syndrome. These substances act on the vessels to produce the symptoms of the carcinoid syndrome.


 * Flushing: The most common finding is flushing of the skin, usually of the head and the upper part of thorax in about 85% of people. The flushing may come and go and may also be triggered by various factors such as diet (i.e. alcohol intake), activity, stress.
 * Diarrhea: The second most common finding occurring in about 80% of people. It may also be associated with abdominal cramping and pain.
 * Bronchoconstriction: A relatively rare symptom affects about 15% of those having carcinoid syndrome and often accompanies flushing, sneezing, and shortness of breath.
 * Heart Disease: About 60-70% of the those affected by carcinoid syndrome develop cardiac complications . This mainly affects the right side of the heart causing fibrosis of the tricuspid and pulmonic valves . This may be heard as a murmur and may contribute to fatigue.

Less common symptoms include malabsorption (leading to pellagra), fatigue, muscle loss, and cognitive impairment. Late complications may include mesenteric and retroperitoneal fibroses as well.

Pathophysiology
The carcinoid syndrome occurs secondary to neuroendocrine tumors. These tumors occur mostly in the gut but may also occur in other places in the body such as the lungs, pancreas, and other organs. Neuroendocrine tumors produce several biologically active substances, mainly amines and peptides. There are over 40 substances known to be secreted by these tumors but the exact affect of each and their contribution to the carcinoid syndrome is unknown. The most common substances found to be released and contribute to the syndrome include serotonin, histamine, tachykinins, kallikrein, and prostaglandins with the greatest contribution appearing to be from serotonin. The symptoms of the carcinoid syndrome result from the action of these substances largely on the blood vessels. These biologic substances are often metabolized and inactivated by the liver in a process known as first pass metabolism. This is why carcinoid syndrome most often occurs in patients whom the neuroendocrine tumor has metastasized to the liver, which allows the substances to bypass the first pass metabolism. Neuroendocrine tumors arising in the bronchi may be associated with manifestations of carcinoid syndrome without liver metastases because their biologically active products reach the systemic circulation before passing through the liver and being metabolized.

Tryptophan metabolism is altered in the carcinoid syndrome. With neuroendocrine tumors, there is a shift in conversion of tryptophan to serotonin from the normal 1% to as high as 70%. Increased amounts of serotonin lead to increased gut motility causing the diarrhea seen in carcinoid syndrome. Increased amounts of serotonin can also cause the flushing seen as the main symptom of carcinoid syndrome. Tryptophan is also needed for niacin synthesis which can be a cause for pellagra associated with carcinoid syndrome. In the pulmonary neuroendocrine tumors or metastases, histamine release and kallikrein metabolism are the vasoactive mediators of flushing and the other symptoms of carcinoid syndrome.

Carcinoid Crisis
Carcinoid crisis is an extreme exacerbation of the carcinoid syndrome. This results from excessive release of amines by the neuroendocrine tumors. It is largely a result of stressful procedures such as anesthesia, surgery, or radiation treatment. Symptoms of carcinoid crisis include flushing, hypotension, arrhythmia and bronchospasm.

Carcinoid Heart Disease
Carcinoid heart disease is the result of valvular damage related to the vasoactive substances released by the neuroendocrine tumor reaching the right side of the heart. This mainly affects the right side of the heart unless there is anomalous circulation (i.e. patent foramen ovale) because the lungs will metabolize the substances released by the tumor similar to how the liver will. After initial tissue injury around the valves, plaque will develop and fibrosis will occur, possibly mediated by excess serotonin.

Diagnosis
With a certain degree of clinical suspicion, the most useful initial test is the 24-hour urine levels of 5-HIAA (5-hydroxyindoleacetic acid), the end product of serotonin metabolism. Chromogramin A, a glycoprotein released by neuroendocrine tumors, can be used to detect non-secreting tumors.

Imaging
Imaging studies should be largely focused on the abdomen and pelvis because the neuroendocrine tumors causing the carcinoid syndrome largely arise in the gut. CT and MRI that utilize radioactive somatostatin analogues such as indium-111 penoctreotide are used to localize the tumor. Bronchoscopy with biopsy can performed if there is evidence of a pulmonary tumor.

Epidemiology
The incidence of neuroendocrine tumors in the US lies somewhere from 2.7 to 4.3 per 100,000 people. The incidence of the carcinoid syndrome is about 0.27 per 100,000 people in the US, about 10% of all people with neuroendocrine tumors. There does not appear to be any variance by gender however patients of African American ethnicity appear to be affected by the carcinoid syndrome more often.

Treatment
Treatment of the carcinoid syndrome is generally done with somatostatin analogues octreotide or lanreotide. These analogues can help control the growth of the tumor itself and the associated symptoms of the carcinoid syndrome. In patients whose symptoms are refractory to initial doses, increasing the dose or switching to another analogue pasireotide may be effective. In patients who continue to be refractory, mTOR inhibitors such as everolimus. The TPH inhibitor telotristat ethyl may be useful in controlling diarrhea associated with the carcinoid syndrome.

Peptide directed radiotherapy (PRRT) is another alternative treatment for patients who failed somatostain analogue therapy. This method uses radioactive somatostatin analogues such as 177Lu-Dotatate or 90Y-Edotreotide to target tumor directly. These therapies are effective for metastatic disease but studies have been limited to about 6 month time periods. Cytoreductive surgery performed chemically with 131metaiodobenzylguanidine (131I-MIBG) may also control symptoms starting around 6-15 months post procedure and lasting as long as 39 months. There are also procedures that target the liver directly such as radiofrequency ablation or radioembolization that deliver targeted therapy directly to the liver through special catheters. This is especially useful for patients with liver metastases.

Carcinoid Heart Disease
The most important aspect of treating carcinoid heart disease is detecting its presence with echocardiography, likely with color doppler. Treatment consists of the same treatment as patients with heart failure with definitive treatment being surgical valve repair or replacement.