The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders
Abstract
Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79±4 to 114±6 bpm), increased systolic blood pressure on standing (from 117±5 to 126±7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157±12 versus 117±9 in normal controls and 119±7 mm Hg in POTS; P =0.048), and an exaggerated phase IV blood pressure overshoot (50±10 versus 17±3 mm Hg in normal controls; P <0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but β-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.
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In the citing paper
“Common comorbid conditions seen with POTS4,21 include hypermobile Ehlers–Danlos syndrome, mast cell activation syndrome,22 migraine and ME/CFS (Table 1).18”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [22]
In the citing paper
“Hyperadrenergic features can include tremulousness, anxiety, migraine and angina-like chest pain.22”
From Diagnosis and management of postural orthostatic tachycardia syndrome (2022) · cites this paper as [22]
In the citing paper
“These episodes resemble those seen in patients with mast cell activation disorders (MCAD). Indeed, we have previously reported the association of MCAD and POTS in patients with a hyperadrenergic clinical phenotype responsive to central sympatholytics.12”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [12]
In the citing paper
“We and others have observed that these patients tend to have exaggerated pressor responses to the Valsalva maneuver (VM),12”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [12]
In the citing paper
“Clinically indistinguishable hyperadrenergic episodes were seen in POTS patients without MCAD12 and are also seen in patients with pseudopheochromocytoma.34,35”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [12]
In the citing paper
“We previously used methyldopa in the treatment of POTS associated with mast cell activation disorders that have a similar hyperadrenergic phenotype.12”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [12]
In the citing paper
“We have previously reported that spontaneous hyperadrenergic episodes with flushing, hypertension, and tachycardia are associated with MCAD in patients with POTS.12”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [12]
In the citing paper
“Treatments that improve symptoms of POTS might decrease the occurrence of syncope, although this is unknown (24,514–523).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [515]
In the citing paper
“An exaggerated sympathetic vasoconstrictor response during the Valsalva maneuver or the presence of orthostatic hypertension may suggest hyperadrenergic POTS (46).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [46]
In the citing paper
“Patients with MCAD may also demonstrate hyperadrenergic POTS features with testing, such as an exaggerated BP overshoot during recovery after the Valsalva maneuver (46).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [46]
In the citing paper
“Some patients with MCAD and associated POTS anecdotally responded to H 1 and H 2 histamine receptor blockers, the sympatholytic alphamethyldopa, or both (46).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [46]
In the citing paper
“Of note, in the same series, beta-blockers triggered episodes of worsening symptoms in several patients and should be used with caution if MCAD is suspected.”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [46]
In the citing paper
“Some POTS patients present with severe flushing in addition to their tachycardia and have an associated mast cell activation disorder.”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [56]
In the citing paper
“While many conditions, such as mast cell activation disorders (9), Ehlers-Danlos syndrome (10, 11), deconditioning (12), and genetic mutations of norepinephrine transporters (13), coexist with POTS, their downstream effects also funnel into these three principal pathophysiologic mechanisms.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [9]
In the citing paper
“Mast cell activation disorders are another condition that frequently coexists with POTS (9).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [9]
In the citing paper
“Some POTS patients may present with flushing and orthostatic intolerance in the absence of mast cell activation disorder”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Shibao et al., 2005
In the citing paper
“a subgroup of POTS patients has been reported to present with episodic flushing and comorbid mast cell activation disorder”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Shibao et al., 2005
In the citing paper
“abnormal sympathetic activation may be related in some patients to the abnormal mast cell activation.”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [57]
In the citing paper
“This specific subset of POTS is characterized by episodes of flushing, dyspnoea, headache, excessive diuresis and gastrointestinal symptoms such as diarrhoea, nausea and vomiting, accompanied by elevated urine methylhistamine [57].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [57]
In the citing paper
“An alternative broader diagnostic scheme125 can lead to overdiagnosis of mast cell activation syndrome as has been described in case reports of POTS and hypermobile Ehlers-Danlos syndrome.”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [125]
In the citing paper
“Exercise is an HRS Class IIA indication for POTS but remains a target of study49,50,125,170,173; its value in IST is unknown.49,50,125”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [125]
In the citing paper
“POTS is excessive sinus tachycardia triggered by minimal physical activity, especially movement to upright posture.36,50,125,171”
From Sinus Tachycardia: a Multidisciplinary Expert Focused Review (2022) · cites this paper as [125]
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“16 Kohno et al. examined 69 patients referred to their medical center for POTS and assessed laboratory and clinical findings that may be associated with comorbid MCAS.”
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BackgroundResultPostural orthostatic tachycardia syndrome
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“Orthostatic intolerance syndromes are common in those with mast cell activation [34], and some forms of POTS have been described in association with mast cell activation disorders [32].”
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“…to small nerve fibers and inflammatory processes [46]; Mast Cell Activation Syndrome (MCAS), involving excessive inflammatory mediator release [47]; Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME), associated with immune dysregulation and chronic inflammation [48]; and…”
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MethodMast Cell Activation Syndromes
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“Orthostatic hypertension in individuals with the POTS, which is characterized by hyper-adrenergic symptoms while standing, supports the idea [13].”
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“Supporting this hypothesis, Shibao et al. [5] showed abnormal MCA in adults with POTS.”
BackgroundMethodInfluentialExercise-induced anaphylaxis in an elderly patient
Namiki, H. (2017) · BMJ Case Reports · doi:10.1136/bcr-2017-222297 · Cited by 3
Risk factors of sitting-induced tachycardia syndrome in children and adolescents
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BackgroundMast cell biology in the context of dysautonomia and neuropathy
Cimolai, N. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108417 · Cited by 3
Postural orthostatic tachycardia syndrome in a Thai male patient
Kulapatana, S., Diedrich, A., Lersritwimanmaen, P., & Watanapa, W. B. (2024) · Clinical Autonomic Research · doi:10.1007/s10286-024-01044-1 · Cited by 2
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Conditions Associated with Median Arcuate Ligament Syndrome: POTS, MCAS, EDS
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Gynaecological Considerations in PoTS
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Dizziness, Syncope, and Autonomic Dysfunction in Children
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“…&Woolf, 1994; Theodorou, Theodorou, Kakitsubata, & Adams, 2012)—are well recognized as being issues which mast cell (MC) activation is capable of driving (e.g., Shibao et al., 2005; Valent et al., 2012) and which indeed are experienced by some MCAS patients (Afrin, Self, Menk, & Lazarchick, 2017).”
BackgroundAutonomic Dysfunction in Dizziness Clinic
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Mast cell activation and autonomic disorders
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Self-citationIs PoTS an Autoimmune Condition?
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Diagnostic et traitement du syndrome de tachycardie orthostatique posturale
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Mechanisms of Postural Tachycardia Syndrome
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“Tests of autonomic nervous system function typically show intact or exaggerated reflex responses though these patients often have preserved vagal function as measured by expiratory: inspiratory (E: I) ratio [6].”
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DETERMINATION OF A PLASMA EMITTER FORM IN AN ACCELERATING ELECTRIC FIELD.
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“우울증, 불안장애 등도 많이 동반되는 증상으로 알려져 있고, 이 역시 질환의 악화요인에 들어간다[10,17,18].”
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Metadata
- Authors
- Shibao, C., Arzubiaga, C., Roberts, L. J., Raj, S., Black, B., Harris, P., & Biaggioni, I.
- Affiliations
- Vanderbilt University (US)
- Venue
- Hypertension
- Published
- 2005-03
- Volume
- 45
- Issue
- 3
- Pages
- 385-390
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2158298420
- Cited by
- 220
- References
- 24
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 15 · 2023: 9 · 2022: 18 · 2021: 13 · 2020: 23 · 2019: 9 · 2018: 21 · 2017: 20 · 2016: 10 · 2015: 5 · 2014: 8 · 2013: 6 · 2012: 7
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL67232, R01HL067232, HL56693, P01HL056693)
- National Center for Research Resources
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- postural orthostatic tachycardia syndrome, mast cell activation, flushing, orthostatic intolerance, Valsalva maneuver, beta-blocker therapy, mast cell mediators, pathogenesis
- MeSH terms
- Adrenergic beta-Antagonists, Adult, Autonomic Nervous System, Female, Histamine H1 Antagonists, Histamine H2 Antagonists, Humans, Hypotension, Orthostatic, Mast Cells, Methyldopa, Sympatholytics, Syndrome, Tachycardia, Case-Control Studies
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