. Author manuscript; available in PMC: 2017 Sep 1.

Published in final edited form as: Rev Endocr Metab Disord. 2016 Sep;17(3):373–380. doi: 10.1007/s11154-016-9394-8

Table 1.

Neuroendocrine causes of flushing.

Diagnosis	Estimates	Clinical findings	Triggers	Substances
Carcinoid syndrome	10% of patients with carcinoid tumors (incidence rate of 1.9 per 100,000)	Flushing Diarrhea Abdominal cramping Fatigue	Amine-rich foods: sherry, beer, fermented foods, and chocolate Medications: catecholamines, dopamine, pentagastrin and isoproterenol Increase in adrenergic activity: as seen in pain, anger, embarrassment, or exertion.	Serotonin Substance P Histamine Catecholamines Prostaglandins
Pheochromocytoma and Paraganglioma	1 in 2500–6500 individuals (500–1600 cases diagnosed annually in the United States)	Hypertension is the most frequent finding (sustained or paroxysmal, or associated with flushing or pallor) The typical PPGL attack, which is seen in approximately 30% of patients, presents headaches, sweating, palpitations, and with or without flushing.	Medications: glucocorticoids or β-adrenergic receptor blockers, glucagon. Increase in adrenergic activity: as seen in pain, anger, embarrassment, or exertion.	Pheochromocytomas: catecholamines (epinephrine, norepinephrine, and dopamine) Paragangliomas: does not produce catecholamines Both may be biochemically silent
Medullary Thyroid Cancer	Rare	Most patients are asymptomatic; in the symptomatic patient, secretory diarrhea is the most prominent hormone-mediated clinical finding, with or without flushing	None	Calcitonin Prostaglandins Histamine Substance P Ketacalcin Levodopa, Adrenocorticotropic hormone Corticotropin-releasing hormone
Pancreatic Neuroendocrine Tumors	<1 per 100 000 persons per year	Most individuals usually only have symptoms relating to the hormone that is chiefly produced.	None	Vasoactive intestinal peptide Gastric inhibitory polypeptide Prostaglandin Insulin Gastrin Glucagon Adrenocorticotropic hormone Corticotropin-releasing hormone Somatostatin Growth hormone–releasing factor Neurotensin Parathyroid hormone-related peptide Pancreatic polypeptide Melanocyte-Stimulating Hormone
Endogenous Cushing syndrome	0.7–2.4 per million population per year	Facial plethora Central body weight gain with limb thinning Acanthosis nigricans Proximal muscle weakness Easy bruising Striae Flushing (rare)	None	Cortisol Adrenocorticotropic hormone and/or Corticotropin-releasing hormone (in Cushing disease or ectopic Cushing syndrome)