The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown.
We conducted a cross-sectional electronic survey of American and ...European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions.
Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%96/132 vs. 32%20/62 of respondents from North America and 24%8/33 of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%96/132, and 42%14/33) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important" concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227).
There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.
A significant minority of patients with hypothyroidism report persistent symptoms despite achieving normal thyroid biochemistry after levothyroxine (L‐T4) replacement. Four principal lines of ...thinking, which are not mutually exclusive, may explain this enigma. The ‘low tissue liothyronine hypothesis’ emphasizes the potential imperfections of L‐T4 replacement therapy that may lead to hypothyroidism in some tissues such as the brain, while others (eg hypothalamus) are euthyroid. The ‘Somatic Symptom and Related Disorders hypothesis’ draws attention to an incidental coexistence of a diagnosis of Somatic Symptom and Related Disorders in patients with treated hypothyroidism. The ‘autoimmune neuroinflammation hypothesis’ highlights the potential consequences of inflammatory mediators due to thyroid autoimmunity (the commonest cause of hypothyroidism) on the brain. The ‘comorbidities and psychosocial hypothesis’ implicates a variety of physical and psychosocial factors that have been noted to be associated with a diagnosis of hypothyroidism, which may be primarily the cause of persistent complaints. Over the past twenty years, a great deal of time and effort has been expended pursuing the ‘low tissue liothyronine hypothesis’, which has failed to yield results that translate to patient benefits. This has skewed the balance in clinical practice, in favour of pursuing answers relating to L‐T4 and liothyronine combination treatment, while the alternative explanations have been downplayed and potentially useful interventions have been given insufficient attention.
Hypertension in Thyroid Disorders Berta, Eszter; Lengyel, Inez; Halmi, Sándor ...
Frontiers in endocrinology (Lausanne),
07/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
Arterial hypertension represents a major global health concern; more than one fourth of the population is affected by high blood pressure. Albeit the underlying cause of the disease remains unclear ...in the vast majority of the cases, ~10% are of secondary origin. Endocrine disorders are common illnesses and some of them may lead to elevated blood pressure, among which thyroid diseases are of high prevalence and often overlooked, especially in mild cases. Overt and subclinical hyper- and hypothyroidism can both lead to (mostly mild) hypertension; however, the underlying mechanisms are only partially understood. The results of clinical studies are often controversial. During the past decades, some genetic mutations in the hypothalamus-pituitary-thyroid axis with cardiovascular consequences were revealed. Atherosclerotic changes resulting from lipid abnormalities due to thyroid dysfunction also affect the vasculature and can cause elevated blood pressure. The review gives a synopsis of our knowledge how thyroid hormone metabolism and functional thyroid diseases affect the cardiovascular system, their negative impact and causative role in the development of hypertension.
Orbital connective tissue changes are contributors to the pathogenesis in thyroid eye disease (TED). Activated fibroblasts respond to immune stimuli with proliferation and increased hyaluronan (HA) ...production. Cyclosporin A (CsA) was reported to be beneficial in the treatment of TED. PDGF isoforms are increased in orbital tissue of TED patients and enhance HA production. We aimed to study the effect of CsA on HA production and hyaluronan synthase (HAS1, 2 and 3) and hyaluronidase (HYAL1 and 2) mRNA expressions in orbital fibroblasts (OFs). Measurements were performed in the presence or absence of CsA (10 μM) in unstimulated or PDGF-BB (10 ng/ml) stimulated OFs. The HA production of TED OFs (n = 7) and NON-TED OFs (n = 6) were measured by ELISA. The levels of mRNA expressions were examined using RT-PCR. The proliferation rate and metabolic activity were measured by BrdU incorporation and MTT assays, respectively. Treatment with CsA resulted in an average 42% decrease in HA production of OFs (p < 0.0001). CsA decreased the expression levels of HAS2, HAS3 and HYAL2 (p = 0.005, p = 0.005 and p = 0.002, respectively.) PDGF-BB increased HA production (p < 0.001) and HAS2 expression (p = 0.004). CsA could reduce the PDGF-BB-stimulated HA production (p < 0.001) and HAS2 expression (p = 0.005) below the untreated level. In addition, CsA treatment caused a decrease in proliferation potential (p = 0.002) and metabolic activity (p < 0.0001). These findings point to the fact that CsA affects HA metabolism via HAS2, HAS3 and HYAL2 inhibition in OFs. In addition to its well characterized immunosuppressant properties, CsA's beneficial effect in TED may be related to its direct inhibitory effect on basal and growth factor stimulated HA production.
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•Cyclosporin A (CsA) inhibits hyaluronan (HA) production in orbital fibroblasts.•CsA decreases the mRNA expressions of the enzymes necessary for HA turnover.•By reducing the amount of HA, CsA directly inhibits the development of oedema in TED.
Takotsubo cardiomyopathy (TTC) is an important complication of subarachnoid hemorrhage (SAH), that may delay surgical or endovascular treatment and may influence patient outcome. This prospective ...follow-up study intended to collect data on the prevalence, severity, influencing factors and long-term outcome of TTC in patients suffering from non-traumatic SAH.
Consecutive patients admitted with the diagnosis of non-traumatic SAH were included. Intitial assessment consisted of cranial CT, Hunt-Hess, Fisher and WFNS scoring, 12-lead ECG, transthoracic echocardiography (TTE), transcranial duplex sonography and collecting laboratory parameters (CK, CK-MB, cardiac troponin T, NT-proBNP and urine metanephrine and normetanephrine). Diagnosis of TTC was based on modified Mayo criteria. TTC patients were dichotomized to mild and severe forms. Follow-up of TTE, Glasgow Outcome Scale assessment, Barthel's and Karnofsky scoring occurred on days 30 and 180.
One hundred thirty six patients were included. The incidence of TTC in the entire cohort was 28.7%; of them, 20.6% and 8.1% were mild and severe, respectively. TTC was more frequent in females (30/39; 77%) than in males (9/39; 23%) and was more severe. The occurrence of TTC was related to mFisher scores and WFNS scores. Although the severity of TTC was related to mFisher score, Hunt-Hess score, WFNS score and GCS, multivariate analysis showed the strongest relationship with mFisher scores. Ejection fraction differences between groups were present on day 30, but disappeared by day 180, whereas wall motion score index was still higher in the severe TTC group at day 180. By the end of the follow-up period (180 days), 70 (74.5%) patients survived in the non-TTC, 22 (81.5%) in the mild TTC and 3 (27%) in the severe TTC group (n = 11) (p = 0.002). At day 180, GOS, Barthel, and Karnofsky outcome scores were higher in patients in the control (non-TTC) and the mild TTC groups than in the severe TTC group.
Takotsubo cardiomyopathy is a frequent finding in patients with SAH, and severe TTC may be present in 8% of SAH cases. The severity of TTC may be an independent predictor of mortality and outcome at 6 months after disease onset. Therefore, a regular follow-up of ECG and TTE abnormalities is warranted in patients with subrachnoid hemorrhage for early detection of TTC.
The study was registered at the Clinical Trials Register under the registration number of NCT02659878 (date of registration: January 21, 2016).
Objective
Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The ...objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones.
Design
Web‐based survey.
Patients
UK endocrinologists were invited to participate.
Measurements
Responses to questionnaire.
Results
The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine‐treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit.
Conclusions
UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.
Background: The incidence and prevalence of hypothyroidism are increasing and the threshold for the treatment of hypothyroid as well as individuals without evident thyroid disease with thyroid ...hormone is declining. Objective: To investigate endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid patients in Italy, a country where different formulations of levothyroxine (LT4; tablet, liquid solution and soft-gel capsule) are available on the market. Methods: Members of the Associazione Medici Endocrinologi (Italian Association of Clinical Endocrinologists) were invited to participate in a web-based survey investigating the topic. Results: A total of 797 of 2,028 (39.3%) members completed all the sections of the survey; 98.7% declared that the treatment of choice for hypothyroidism is LT4. A significant minority (37.3%) indicated that LT4 may be considered in infertile euthyroid women seeking pregnancy and harbouring positive thyroperoxidase antibodies (TPOAb) and in goitre increasing in size (18.1%). LT4 + LT3 was considered by 43.2% for LT4-replaced patients and normal TSH, if they reported persistent symptoms. High percentages of respondents chose LT4 in a liquid solution or soft-gel capsules when taken together with other drugs interfering with LT4 absorption (81.8%), in patients with a history of celiac disease, malabsorption, lactose intolerance, intolerance to common excipients (96.6%), or unexplained poor biochemical control of hypothyroidism (74.4%), or in patients not able to adhere to ingesting LT4 fasted and/or separated from food/drink (98.9%). In total, 43.6% of responders would use LT4 in a liquid solution or soft-gel capsules for hypothyroid patients with biochemical euthyroidism on LT4, who had persistent symptoms. Conclusions: The preferred treatment for hypothyroidism is LT4; LT3 + LT4 combination treatment is mainly considered in patients with persistent symptoms. A significant minority would offer LT4 to euthyroid women with positive TPOAb and infertility and to euthyroid patients with progressive simple goitre. Alternative LT4 formulations like liquid solution or soft-gel capsules are largely reserved for specific conditions (interfering drugs, actual or suspected malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism).
Thyroid autoimmunity in Graves’ disease (GD) is accompanied by Graves’ orbitopathy (GO) in 40% of the cases. Orbital fibroblasts (OF) play a key role in the pathogenesis and cigarette smoking is a ...known deteriorating factor. Alongside conventional cigarettes (CC) new alternatives became available for smokers, including heated tobacco products (HTP) and E-cigarettes (ECIG). We aimed to study the cellular effects of smoke extracts (SE) in orbital fibroblasts. Primary OF cultures from GO and NON-GO orbits were exposed to different concentrations of SE (1%, 50%) and the changes were followed using Real Time Cell Electronic Sensing (RT-CES). Untreated GO and NON-GO cells had different maximum cell index (CI) values of 3.3 and 2.79 respectively (p < 0.0001). CC, HTP and ECIG treated NON-GO fibroblasts exhibited peak CIs of 2.62, 3.32 and 3.41 while treated GO cells’ CIs were higher, 5.38, 6.25 and 6.33, respectively (p < 0.0001). The metabolic activity (MTT) decreased (p < 0.001) and hyaluronan production doubled (p < 0.02) after 50% of CC SE treatment in all cell cultures. GO fibroblasts were more sensitive to low concentration SE then NON-GO fibroblasts (p < 0.0001). The studied SEs exerted different effects. RT-CES is a sensitive technique to detect the effects of very low concentration of SE on fibroblasts.
Background
Replacement of thyroid hormones (TH) with Levothyroxine (LT4) is the treatment of choice for hypothyroidism, however, there are aspects of treatment where uncertainties exist and practice ...varies. Factors influencing initiation and choice of TH replacement may impact patient satisfaction, safety, and health care costs.
Methods
The aim of the study was to examine the attitudes of Irish endocrinologists regarding the treatment of hypothyroid and euthyroid patients with TH. Members of the Irish Endocrine Society (IES) were invited to participate in an online survey.
Results
Forty-eight invitations were sent, and 39 (81.3%) participants responded. All respondents favoured LT4 tablet therapy for treatment of hypothyroidism, but 20.5% prescribed combination therapy (LT4 and liothyronine), and 13% regularly used desiccated thyroid extract. A significant proportion (51%) might prescribe TH in euthyroid patients; 41% for thyroid auto-antibody positive women seeking pregnancy, 18% for goitre and 5% for unexplained fatigue. Many (38%) consider combination therapy in patients with persistent symptoms. Respondents reported seeing LT4 treated patients with persistent symptomatology more frequently and perceive psychosocial factors and comorbidities to be the most common reasons for such symptoms.
Conclusion
LT4 tablets are the treatment of choice for hypothyroidism in Ireland. Approximately a third of Irish endocrinologists either regularly use, or would consider, liothyronine for hypothyroid patients. A significant proportion would give TH to euthyroid individuals in specific circumstances. The prescription of TH amongst Irish endocrinologists was generally in keeping with recommended practice, and areas where practice deviated from guidance were typically where evidence was conflicting or insufficient.
Takotsubo syndrome (TS) is a frequent complication of subarachnoid hemorrhage (SAH), especially in massive SAH with severe neurological damage. The initial presentation of TS is similar to acute ...coronary syndrome, causing differential diagnostic issues. Unnecessary diagnostic steps and uncertainty in therapy may delay the definitive treatment of the aneurysm, therefore increasing the risk of rebleeding. The purpose of this review is to summarize the latest knowledge on the diagnosis and therapy of TS in SAH and to provide a diagnostic and therapeutic algorithm for the acute phase, promoting the early definitive treatment of the aneurysm. Rapid hemodynamic stabilization and early aneurysm securing are key points in reducing the risk of delayed cerebral ischemia and improving outcomes. In acute SAH noninvasive bedside diagnostic methods are preferred and securing the aneurysm is the priority. The combination of electrocardiography, cardiac biomarkers, and echocardiography is of great importance in differentiating TS from acute myocardial infarction. The risk-benefit ratio of coronary angiography should be carefully and individually considered and its use should be limited to patients with strong evidence of myocardial ischemia, after the successful endovascular treatment of the aneurysm. Invasive hemodynamic monitoring may be beneficial in cases of cardiogenic shock or pulmonary edema. In patients with hemodynamical instability secondary to TS, the use of non-catecholamine inotropes, especially levosimendan is recommended. In refractory hypotension, mechanical support should be considered. The left ventricular function improves within days to months after the acute event, low initial ejection fraction may predispose to delayed recovery.Takotsubo syndrome (TS) is a frequent complication of subarachnoid hemorrhage (SAH), especially in massive SAH with severe neurological damage. The initial presentation of TS is similar to acute coronary syndrome, causing differential diagnostic issues. Unnecessary diagnostic steps and uncertainty in therapy may delay the definitive treatment of the aneurysm, therefore increasing the risk of rebleeding. The purpose of this review is to summarize the latest knowledge on the diagnosis and therapy of TS in SAH and to provide a diagnostic and therapeutic algorithm for the acute phase, promoting the early definitive treatment of the aneurysm. Rapid hemodynamic stabilization and early aneurysm securing are key points in reducing the risk of delayed cerebral ischemia and improving outcomes. In acute SAH noninvasive bedside diagnostic methods are preferred and securing the aneurysm is the priority. The combination of electrocardiography, cardiac biomarkers, and echocardiography is of great importance in differentiating TS from acute myocardial infarction. The risk-benefit ratio of coronary angiography should be carefully and individually considered and its use should be limited to patients with strong evidence of myocardial ischemia, after the successful endovascular treatment of the aneurysm. Invasive hemodynamic monitoring may be beneficial in cases of cardiogenic shock or pulmonary edema. In patients with hemodynamical instability secondary to TS, the use of non-catecholamine inotropes, especially levosimendan is recommended. In refractory hypotension, mechanical support should be considered. The left ventricular function improves within days to months after the acute event, low initial ejection fraction may predispose to delayed recovery.
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