Carcinoid tumours originate from hormone-producing cells in the digestive system or lungs and can cause carcinoid syndrome. Carcinoid syndrome is characterized by flushing, diarrhea, and other symptoms due to excess hormone production. Diagnosis involves tests of urine or blood for biomarkers like 5-HIAA. Treatment focuses on reducing symptoms using somatostatin analogues and potentially includes procedures to reduce tumour size. Management of carcinoid syndrome requires a multidisciplinary approach.

1. Carcinoid Syndrome and
Endocrinology
Dr Vikram Singh Chauhan(MD, DM)
Consulting Endocrinologist: Dr
Chauhan’s Clinic and Jabalpur Hospital
& Research Center, Jabalpur

2. Carcinoid Tumours and Syndrome
• Carcinoid tumours (neuroendocrine
neoplasms) usually originate in hormone-
producing cells that line the small intestine or
other parts of the digestive tract; also occur in
the pancreas, lungs (bronchial carcinoid);
rarely testes or ovaries
• Carcinoid syndrome: diverse set of symptoms
due to excess hormones produced by
carcinoid tumours

3. Epidemiology
• Occurs mainly in gastrointestinal or lung related
NEN
• Incidence of carcinoid syndrome- 1 :100 000
population¹
• Carcinoid syndrome: prevalence of ~20% in
NENs²
• Small intestine(42%), rectum(27%),
bronchopulmonary(25%), stomach(8.7%)3
1. The Lancet Oncology, 18(4), 525–534. 2017
2. Neuroendocrinology, 90(4) 349–363 2009
3. Cancer 97:934–959 2003

4. • Carcinoid syndrome function of:
-- Tumour mass
-- extent and localization of metastases
-- localization of the primary tumour
• Most common in tumours originating in small
intestine and proximal colon: 40%-60% patients
with these tumours experience syndrome¹
• Less common: bronchial, midgut, rectal
• Syndromic patients: liver metastasis²
1. Am J Cardiol. 21:376-387 1968 2. J Am Med Assoc. 186:905-907 1963

5. Clinical Features
• Diarrhoea: occurs in ~80%
• Secretory– fluid & electrolyte imbalance
possible
• Due to increased GI motility caused by
hormones of tumour: serotonin, tachykinins,
histamines, kallikrein, and prostaglandins,
can stimulate peristalsis, electromechanical
activity and intestinal tone
Semin Gastrointest Dis. 10:156-172 1999

6. Clinical Features
• Flushing: ~70%
• 4 described types:
-- Erythematous: midgut carcinoid, disease onset
-- Violaceous: midgut carcinoid, later stages
-- Prolonged: malignant bronchial carcinoids
-- Bright red: gastric carcinoids(ECLomas)
• Usual areas: face, neck, and upper chest
Am J Cardiol. 21:376-387 1968

7. Clinical Features
Precipitating factors for flushing:
--Stress
-- Stimulation of the vagus nerve by brushing
of teeth or mastication
-- Ingestion of alcohol or tyramine-containing
foods such as cheese, coffee, chocolate, nuts,
avocado, bananas, and red wine
EurJ Endocrinol 177(5): 219–229 2017

8. J Am Acad Dermatol. 2006. 55(2): 193-208

9. Clinical Features
• Abdominal Pain: ~40%; related to mesenteric
fibrosis
• Wheezing/bronchospasm: 10-20%; related to
hormone excess
• Palpitations: upto 30 minutes
• Itching/skin rashes: histamine related
Endocrine Reviews, vol. 25, no. 3, pp. 458–511, 2004

10. Clinical Features
• Carcinoid Heart Disease: plaque-like
thickenings of the endocardium, valve leaflets,
atria, and ventricles¹,2
• 10% to 20% of the patients1,2
• Stenosis and regurgitation
• New collagen beneath endothelium of
endocardium: almost pathognomonic for
carcinoid heart disease1
1. Circulation. 77:264-269 1988
2. Am J Med. 36:5-34 1964

11. Clinical Features
• Carcinoid Heart Disease: Right sided fibrosis—
in patients with liver metastases who usually
also have the carcinoid syndrome
• Correlation between circulating levels of
serotonin and tachykinins and degree and
frequency of carcinoid heart lesions
• NT-proBNP: best diagnostic and prognostic
marker of carcinoid heart disease1
1. Int J Cardiol. 173:29-32 2014

12. Carcinoid Crisis
• Spontaneously or during induction of anesthesia,
embolization procedures, chemotherapy, or
infection
• Characterized by
--Severe flushing
--Diarrhea
--Hypotension
--Hyperthermia
--Tachycardia
• Octreotide (IV or SC) given pre, intra, and post op
N Engl J Med. 313:1229-1230 1985

13. Clinical Features
• Cushing syndrome: ectopic ACTH/CRH--
pulmonary and thymic carcinoids
• Acromegaly: ectopic GHRH-- foregut carcinoids
• Gastric carcinoids:
--Type 1—chronic atrophic gastritis
--Type 2– ZES
--Type 3– sporadic, more malignant, no
hypergastrinemia

14. Biosynthesis of Serotonin

15. Classification

16. Classification

17. Classification of Carcinoid Tumours
Williams Textbook of Endocrinology(14th Ed., pg 1693)by S Melmed, Elsevier.

18. Diagnosis
• 24 hour urinary 5HIAA
• Less sensitive, more specific
• Serum CgA: more sensitive and less specific
than urinary 5HIAA
• Platelet serotonin levels
• Plasma NSE: less sensitive and specific than
CgA; useful in lung NENs and NENs with higher
proliferation

19. Interferences in 5HIAA Assays
False positive False negative
Endocrinology: Adult and Pediatric (7th ed., pg 2623)by JL Jameson, 2016, Elsevier Saunders.

20. Localization
• Whole-body SRS: preferred initial modality
earlier: 111In-DTPA-Phe-octreotide
(Octreoscan)
• 68Ga-DOTATATE/TOC-PET scanning: higher
sensitivity than Octreoscan
• CT/MRI: for liver metastasis
• 18F-DOPA-PET scanning using 11C5HTP: useful
to monitor therapy results
International Journal of Endocrine Oncology, 6(2). https://doi.org/10.2217/ije-
2019-0001

21. Treatment
• Tumour reduction and symptomatic control
• Long-acting somatostatin analogues:
cornerstones
• Bind to SSTR1, SSTR5, SSTR3: Lower growth factor
production & antiproliferative effect
• Octreotide, Octreotide LAR, Lanreotide
• Reduction in tumour size demonstrated with high
dose therapy
• Tachyphylaxis, GI side effects, gallstone
development

22. Treatment
• Interferon alpha 2a and alpha 2b
• Biochemical control and size reduction
• Can be combined with somatostatin
analogues
• Chronic fatigue syndrome, anemia,
luekopenia, thrombocytopenia, autoimmunity
development

23. Treatment
• Chemotherapy:
--Streptozotocin plus 5-fluorouracil
--Doxorubicin
--Cisplatin plus etoposide
--Dacarbazine plus 5-fluorouracil
--Temozolomide
• Attempted in foregut carcinoids(more
malignant)
• Cancer. 68:227-232 1991
• Ann Oncol. 6:77-79 1995
• Cancer. 83:372-378 1998
• Clin Cancer Res. 13:2986-2991 2007

24. Treatment
• Surgery: Debulking procedures
• Resection of local disease
• Hepatic artery embolization

25. Treatment
• External beam irradiation: palliative for brain
and bone mets
• Somatostatin analogue–based tumor-targeted
radioactive treatment: 125I-MIBG or 131I-MIBG,
111In-DTPA-octreotide, 90Y-DOTA-octreotide,
177Lu-DOTA-octreotate

26. Management: Proposed Algorithm
J Oncol.2020;2020:8341426

27. Thank You Very Much