2.2. Challenges in diagnosis

← PREVIOUS: [[2.1. Diagnostic criteria for POTS]] | NEXT: [[2.3. Diagnostic approaches and biomarkers]] → -------- ##### Summary >[!Summary] >- emphasis on 'postural tachycardia' has a disadvantage, because it ignores nonorthostatic symptoms[[#^1]] >- diagnosis difficult because it requires doctor's vigilance combined with knowledge about the syndrome and access to cardiovascular autonomic tests[[#^2]] >- complicating factor is heterogeneity of symptoms that may mask underlying POTS and divert clinician's attention towards other conditions with similar presentation (e.g. anxiety disorders, hyperthyroidism, phenochromocytoma, astehania, orthostatic hypotension, hypocortisolaemia or other endocrinological disorder[[#^2]], acute hypovolemia, anemia, adverse effects from medication, etc. [[#^17]]) >- there is also a significant overlap in symptomatology between POTS and CFS (chronic fatigue syndrome) and fibromyalgia, making the distinction between them blurred[[#^23]] >- 2/3 patients report at least 10 different symptoms, which makes diagnosis cumbersome for an untrained practitioner[[#^8]][[#^21]][[#^22]] >- many may not receive diagnosis at all, since many people cannot afford to see multiple doctors and some healthcare systems or insurance providers do not allow multiple 'second opinions'[[#^7]] >- patients wait approximately 4 years from presentation to obtain the correct diagnosis and a suspicion about psychiatric condition is common[[#^9]] >- median diagnostic delay is 24 months (4.9 ± 7.1 years) after initial presentation to a physician[[#^12]] ; median of 4 years (ranging from 1 to 14 years)[[#^20]] >- 15% not diagnosed for more than 10 years after initially visiting a physician[[#^12]] > - despite recent improvement, the average diagnostic delay since 2009 is still over 4.7 ± 6.9 years (median 23 months)[[#^12]][[#^15]] >- 75% misdiagnosed prior to POTS diagnosis[[#^6]] > - 34% suggested POTS diagnosis to physician[[#^6]] > - 67% encountered physicians who acknowledged a physical illness but were unsure how to proceed[[#^14]] > - on average 7 ± 11 physicians seen prior to diagnosis (21% see more than 10 doctors prior to diagnosis)[[#^11]] > - on average 9 ± 16 ED visits prior to diagnosis[[#^6]] > -------------- > **Misconception About Psychological Profile** > - not being believed is a substantial challenge, with physical symptoms often dismissed as being psychosomatic[[#^18]] or caused by anxiety/substance abuse[[#^19]] > - 77% encountered physician who suggested the symptoms were due to a psychiatric or psychological problem, while only 28% were actually suffering from a psychiatric or psychological problem[[#^14]] >- POTS symptoms can mimic symptoms of depression or anxiety, but they are phenomenologically different from symptoms of panic disorder or anxiety. These diseases must be clinically distinguished to avoid misinterpretation of POTS as an anxiety disorder[[#^27]][[#^30]] >- HR response not caused by anxiety, but physiological response that maintains arterial pressure during venous pooling[[#^24]][[#^33]] >- POTS patients do not have increased current or lifetime prevalence of depression [[#^25]][[#^28]] nor anxiety disorders [[#^29]][[#^31]] >- Psychological and somatic symptoms (such as tremor, palpitation, sleep problems and fatigue) are due to the hyperadrenergic state and the disease itself and not of a depressive or anxiety disorder[[#^26]][[#^32]][[#^34]] >- patients sometimes diagnosed as having anxiety disorders, however since somatic symptoms may overlap with hyperadrenergic states, anxiety attributed to patients might be due to misinterpretation of physical symptoms[[#^35]][[#^36]] -------- >*“an excessive HR increment appears to be the earliest and most consistent of the easily measured indices of orthostatic intolerance.7 Most of the other terms focus on manifestations that are not consistently present. The term idiopathic hypovolemia is unsatisfactory, since most patients do not have reduced plasma volumes or red cell mass. Current thinking is that the occurrence of mitral valve prolapse with POTS is fortuitous. The emphasis on postural tachycardia does, however, have a disadvantage in that it ignores nonorthostatic symptoms such as paroxysmal episodes of autonomic dysfunction, including sinus tachycardia, BP fluctuations, vasomotor (especially acral) symptoms, and fatigue.” *([[Low-2009]], [p. 2](zotero://open-pdf/library/items/I4WAD8AG?page=2&annotation=MY6KA8B2))^1 >*“The diagnosis of POTS is difficult as it usually requires both doctor’s vigilance combined with knowledge about the syndrome and an access to cardiovascular autonomic tests. A complicating factor is heterogeneity of symptoms that may mask the underlying POTS and divert clinician’s attention towards other conditions with a similar presentation such as anxiety disorders, hyperthyroidism, pheochromocytoma, asthenia, orthostatic hypotension, hypocortisolaemia or other endocrinological disorders.” *([[Fedorowski-2019]], [p. 8](zotero://open-pdf/library/items/BZ35QDLR?page=8&annotation=EH3M3BZ5))^2 ##### Differential Diagnosis >*“Vasovagal syncope and POTS overlap clinically, and both diagnoses may be appropriate for a given patient [8]. A HUT test can be helpful in the differential diagnosis” *([[Garland-2015]], [p. 6](zotero://open-pdf/library/items/CAWTWYLR?page=6&annotation=4JPNUWTV))^3 >*“IST differs from POTS in that the tachycardia can be independent of body position, and resting HR commonly exceeds 100 beats/min, consistent with higher sympathetic tone and decreased parasympathetic tone in IST relative to patients with POTS and healthy controls” *([[Garland-2015]], [p. 6](zotero://open-pdf/library/items/CAWTWYLR?page=6&annotation=97RWQBSF))^4 >*“POTS can be confused with pheochromocytoma because of the paroxysms of hyperadrenergic symptoms (e.g., palpitations and lightheadedness).” *([[Raj-2013]], [p. 5](zotero://open-pdf/library/items/CCJLQKRB?page=5&annotation=SA6RRBA6))^5 ##### Diagnostic Delay >![[Shaw-2019-5-x67-y126.png#invert_B| 400]] >([[Shaw-2019]], [p. 5](zotero://open-pdf/library/items/48AJ3KVL?page=5&annotation=KV98QCWE))^6 >*“many individuals suffering from POTS may not receive a diagnosis at all, since many people cannot afford to see multiple doctors, and some healthcare systems or insurance providers do not allow multiple ‘second opinions” *([[Shaw-2019]], [p. 8](zotero://open-pdf/library/items/48AJ3KVL?page=8&annotation=MTSLWCEU))^7 >*“Two of three patients report at least ten different symptoms [32], which makes the diagnosis cumbersome for an untrained practitioner.” *([[Fedorowski-2019]], [p. 4](zotero://open-pdf/library/items/BZ35QDLR?page=4&annotation=WF9R2INE))^8 >*“In an UK study, patients waited approximately 4 years from presentation to obtain the correct diagnosis and a suspicion about psychiatric condition was common” *([[Fedorowski-2019]], [p. 4](zotero://open-pdf/library/items/BZ35QDLR?page=4&annotation=UGGBNKAU))^9 >*“POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving.” *([[Shaw-2019]], [p. 1](zotero://open-pdf/library/items/48AJ3KVL?page=1&annotation=699LUHUC))^10 >*“Participants frequently reported being misdiagnosed with other diagnoses, seeing many physicians prior to being diagnosed with POTS, and having to suggest POTS as a potential diagnosis to *([p. 3](zotero://open-pdf/library/items/48AJ3KVL?page=3&annotation=RIALDVQY)) their physician. On average, patients saw 7 ± 11 [median 5 (IQR 3–8)] physicians prior to a diagnosis of POTS. Furthermore, 21% (n = 627) of participants reported having seen more than 10 doctors before a diagnosis was made.” ([[Shaw-2019]], [p. 4](zotero://open-pdf/library/items/48AJ3KVL?page=4&annotation=XW68BZCV))^11 >*“Survey respondents frequently reported lengthy delays until diagnosis (Table S2). Respondents waited a median time of 24 (IQR 6–72) months (4.9 ± 7.1 years) after initial presentation to a physician before a POTS diagnosis was made (Fig. 3a). Approximately 15% of patients were not diagnosed for more than 10 years after initially visiting a physician for their symptoms. Female participants reported longer diagnostic delays (5.0 ± 7.2 years) compared with males (3.0 ± 4.4 years) with POTS (P < 0.001). There were no differences in diagnostic delay between races (P = 0.59). There has been a recent improvement in diagnostic delay. The delay period was 11.6 (95% CI: 2.2, 21.0) months shorter for patients diagnosed after 2009 compared to those diagnosed from 2000 to 2009 (P = 0.01; Fig. 3b). Despite this improvement, the average diagnostic delay since 2009 is still over 4.7 ± 6.9 years [median 23 (IQR 6–69) months].” *([[Shaw-2019]], [p. 4](zotero://open-pdf/library/items/48AJ3KVL?page=4&annotation=YYNNR3DT))^12 >*“Three-quarters (n = 3421; 75%) of patients report that their POTS symptoms were misdiagnosed by a physician prior to being diagnosed with POTS.” *([[Shaw-2019]], [p. 4](zotero://open-pdf/library/items/48AJ3KVL?page=4&annotation=HIIQ3UW2))^13 >*“Prior to POTS diagnosis, many participants (n = 3257; 67%) encountered physicians who acknowledged a physical illness but were unsure how to proceed. There were 3471 (77%) respondents who encountered a physician who suggested their symptoms were due to a psychiatric or psychological problem before they were diagnosed with POTS. In contrast, only 1247 (28%) respondents report they were actually suffering from a psychiatric or psychological problem before they were diagnosed with POTS. After the diagnosis of POTS, only 1656 (37%) participants reported being told that they were suffering from a psychiatric or psychological problem, and 1392 (31%) reported that they were being actively treated for a psychiatric or psychological problem.” *([[Shaw-2019]], [p. 5](zotero://open-pdf/library/items/48AJ3KVL?page=5&annotation=RAZBZ3SU))^14 >![[Shaw-2019-6-x35-y235.png#invert_B| 800]] >([[Shaw-2019]], [p. 6](zotero://open-pdf/library/items/48AJ3KVL?page=6&annotation=3BLYPXJ3))^15 >![[Zotero/Zotero Images/Raj-2022-2-x303-y524.png#invert_B| 450]] >([[Raj-2022]], [p. 2](zotero://open-pdf/library/items/YN8BG2FZ?page=2&annotation=64XJU28N))^17 >*“most experienced some diagnostic delay or misdiagnosis, mainly as mental health conditions, such as anxiety, or in Anna’s case substance abuse. These findings are congruent with existing literature on POTS, with one of the most common misdiagnoses being anxiety”* ([[Knoop-2023]], [p. 6](zotero://open-pdf/library/items/P2VFKVHY?page=6&annotation=2RU5FKUA))^19 >*“In the current study, time to diagnosis ranged from 1 to 14 years, with a median of 4 years, which is somewhat higher than the 1.82 years reported a US study [3]. These aspects of diagnosis and delay are of importance, as previous research indicates that they can have negative consequences for QoL, and depression [4,23].”* ([[Knoop-2023]], [p. 6](zotero://open-pdf/library/items/P2VFKVHY?page=6&annotation=VLJJVUBM))^20 >*“Due to the complexity and heterogeneity in the presentation of this syndrome, POTS patients are often subjected ([p. 1](zotero://open-pdf/library/items/HLELIN7I?page=1&annotation=IAGPTEAS)) to extensive and unnecessary investigations, with fragmented care provided by multiple specialists.”* ([[Wells-2017]], [p. 2](zotero://open-pdf/library/items/HLELIN7I?page=2&annotation=SFGQ2HCK))^21 >*“The range of complex nonspecific symptoms experienced by patients with POTS can be a challenge.”* ([[Wells-2017]], [p. 3](zotero://open-pdf/library/items/HLELIN7I?page=3&annotation=H55EDHD8))^22 >*“The distinction between chronic fatigue syndrome, fibromyalgia and POTS is often blurred, with a significant overlap in symptomatology. Diagnostic criteria for POTS may be met in patients with chronic fatigue syndrome and fibromyalgia only on days when the fluid intake is lower or symptom burden is high.”* ([[Wells-2017]], [p. 3](zotero://open-pdf/library/items/HLELIN7I?page=3&annotation=GFETHAS2))^23 ##### Misconception About Psychological Profile >*“Not being believed was a substantial challenge, with physical symptoms often dismissed as being psychosomatic.”* ([[Knoop-2023]], [p. 4](zotero://open-pdf/library/items/P2VFKVHY?page=4&annotation=37LY8LB6))^18 >*“although anxiety is commonly present in POTS, the HR response to orthostatic stress in POTS patients is not caused by anxiety, but is a physiological response that maintains arterial pressure during venous pooling” *([[Low-2009]], [p. 5](zotero://open-pdf/library/items/I4WAD8AG?page=5&annotation=WX37FRPK))^24 >*“Many people with POTS have mild depression, but not at rates higher than the general population”* ([[Pederson-2018a]], [p. 1](zotero://open-pdf/library/items/M2CWX5ZN?page=1&annotation=NK4PHE2W))^25 >*“There was a positive correlation between BAI and BDI‑II scores and NE increase. The symptoms listed in the BAI include both psychological and somatic symptoms, such as tremor, palpitation, sleep problems and fatigue, which are very common in PoTS and may be a symptom of the hyperadrenergic state and the disease itself, but not of a depressive or anxiety disorder.”* ([[Maier-2023]], [p. 8](zotero://open-pdf/library/items/LQMXCPGX?page=8&annotation=U9K5GIKM))^26 >*“These results show that the scores alone must be interpreted with caution [3, 45], especially in patients with PoTS, because PoTS symptoms can mimic symptoms of depression or anxiety. Patients with higher NE levels might score higher in the BAI due to more somatic symptoms caused by PoTS. As symptoms of PoTS are phenomenologically different from symptoms of panic disorder or anxiety, these diseases must be clinically distinguished [46] to avoid misinterpretation of PoTS as an anxiety disorder.”* ([[Maier-2023]], [p. 8](zotero://open-pdf/library/items/LQMXCPGX?page=8&annotation=3SCM2P2S))^27 >*“Using structured clinical interview, Raj et al. found that adult POTS patients did not experience higher current or lifetime prevalence of major depressive disorder.”* ([[Raj-2018]], [p. 3](zotero://open-pdf/library/items/IYRK4T6C?page=3&annotation=BUYE2RTY))^28 >*“POTS was not more prevalent in patients with psychiatric disorders compared with healthy subjects,”* ([[Raj-2018]], [p. 4](zotero://open-pdf/library/items/IYRK4T6C?page=4&annotation=IAWS8R9L))^29 >*“These symptoms are strongly somatic, and not psychological, suggesting symptoms in POTS are phenomenologically distinct from panic disorder.”* ([[Raj-2018]], [p. 5](zotero://open-pdf/library/items/IYRK4T6C?page=5&annotation=EZ6TARLW))^30 >*“Raj et al. found that adult POTS patients did not have increased current or lifetime prevalence of anxiety disorders.”* ([[Raj-2018]], [p. 5](zotero://open-pdf/library/items/IYRK4T6C?page=5&annotation=DTNQ5Q69))^31 >*“They concluded that the clinical appearance of anxiety in POTS was likely related to the illness rather than representing an anxiety disorder”* ([[Raj-2018]], [p. 5](zotero://open-pdf/library/items/IYRK4T6C?page=5&annotation=Y5S4BJXD))^32 >*“They deduced that anxiety is not the primary cause of excessive orthostatic tachycardia in POTS”* ([[Raj-2018]], [p. 6](zotero://open-pdf/library/items/IYRK4T6C?page=6&annotation=TJX9FXVF))^33 >*“while POTS patients are commonly perceived to be anxious, studies suggest this is largely driven by orthostatic symptoms that overlap with common anxiety symptoms”* ([[Raj-2018]], [p. 6](zotero://open-pdf/library/items/IYRK4T6C?page=6&annotation=MMKL8UDL))^34 >*“Patients with POTS are sometimes clinically diagnosed as having anxiety disorders such as panic disorder. When assessed using a structured evaluation for Diagnostic & Statistical Manual (DSM) 4-TR criteria, POTS patients did not have a higher incidence of major depressive disorder, anxiety disorders, or substance abuse than the general population 7. When assessed using the Beck Anxiety Inventory (BAI), patients report elevated anxiety scores (23±10 vs. 7±8; P<0.001) 7. However, the BAI scores both somatic anxiety & psychological symptoms, which is a problem since somatic symptoms may overlap with hyperadrenergic states (as is seen in POTS). When POTS patients were assessed with a psychological-based measure of anxiety (Anxiety Sensitivity Index), there was a trend toward less anxiety in the patients than the general population (15±10 vs. 19±9; P=0.063) 7. It is possible that some of the anxiety attributed to patients with POTS might be due to a misinterpretation of their physical symptoms.”* ([[Raj-2013]], [p. 2](zotero://open-pdf/library/items/CCJLQKRB?page=2&annotation=YBEYY9B9))^35 >*“Patients with POTS commonly present with symptoms of depression and anxiety. Yet a structured evaluation using criteria from the Diagnostic and Statistical Manual (fourth edition, text revision) did not identify a higher incidence of major depressive disorder, anxiety disorders, or substance abuse in POTS patients than the general population [27]. Furthermore, the HR increase in patients is not a response to anxiety [28]. The palpitations, hyperventilation, and tremulousness of POTS can be misinterpreted as symptoms of anxiety.”* ([[Garland-2015]], [p. 4](zotero://open-pdf/library/items/CAWTWYLR?page=4&annotation=WZ9DLERF))^36 -------- Tags: #diagnosis #challenges