Original Article A SURVEY OF CLINICAL PRACTICE PATTERNS IN MANAGEMENT OF GRAVES DISEASE IN THE MIDDLE EAST AND NORTH AFRICA Salem A. Beshyah, PhD, FRCP, FACP, FACE1; Aly B. Khalil, MD, FRCPC, FACP, FACE2; Ibrahim H. Sherif, FRCPE3; Mahmoud M. Benbarka, MD, FACP, FACE4; Syed Abbas Raza, MD, FACP, FACE5; Wiam Hussein, MD, FACP, FACE6; Ali S. Alzahrani, MD, FACP, FACE7; Asma Chadli, MD8 ABSTRACT Objective: Graves disease (GD) is commonly seen in endocrine clinical practice. The objective of this study was to evaluate the current diagnosis and management of patients with GD in the Middle East and North Africa (MENA). Methods: An electronic survey on GD management was performed using an online questionnaire of a large pool of practicing physicians. Responses from 352 eligible and willing physicians were included in this study. They were mostly endocrinologists (157) and internal medicine physicians (116). Results: In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request serum antithyroid peroxidase antibody and TSH-receptor autoantibody (50% and 46%, respectively), whereas serum antithyroglobulin antibodies would be ordered by fewer respondents (36%). Thyroid ultrasound would be requested by a high number of respondents
Submitted for publication September 22, 2016 Accepted for publication November 10, 2016 From the 1Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 2Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates; 3Al-Afia Clinic, Tripoli, Libya; 4Health Plus, Abu Dhabi, United Arab Emirates; 5Shaukat Khanum Hospital, Lahore, Pakistan; 6Dr Wiam Clinic, Manama, Bahrain; 7King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 8Service d’Endocrinologie et Maladies Métaboliques, CHU Ibn Rochd, Casablanca, Morocco. Address correspondence to Dr. Salem A. Beshyah, PhD, FRCP, FACP, FACE; Centre for Diabetes and Endocrinology, Sheikh Khalifa Medical City, Karamah Street, Abu Dhabi, UAE. E-mail:
[email protected] Published as a Rapid Electronic Article in Press at http://www.endocrine practice.org on December 14, 2016. DOI:10.4158/EP161607.OR To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2017 AACE.
Copyright © 2017 AACE
(63.7%), while only a small percentage would order isotopic thyroid studies. Antithyroid drug (ATD) therapy was the preferred first-line treatment (52.7%), followed by radioiodine (RAI) treatment (36.8%), b-blockers alone (6.9%), thyroidectomy (3.2%), and no therapy (1.3%). When RAI treatment was selected in the presence of mild Graves orbitopathy and/or associated risk factors for its occurrence/ exacerbation, steroid prophylaxis was frequently used. The preferred ATD in pregnancy was propylthiouracil in the first trimester and carbimazole in the second and third trimesters. On most issues, choices of the MENA physicians fell between European and American practices. Conclusion: Hybrid practices are seen in the MENA region, perhaps reflecting training and affiliations. Management approaches most suitable for patients in this region are needed. (Endocr Pract. 2017;23:299-308) Abbreviations: ATD = antithyroid drug; CBZ = carbimazole; FT3 = free T3; FT4 = free T4; GD = Graves disease; GO = Graves orbitopathy; MENA = Middle East and North Africa; MMI = methimazole; RAI = radioactive iodine; RAIU = RAI uptake; T3 = tri-iodothyronine; T4 = thyroxine; TG Ab = antithyroglobulin antibodies; TRAb = TSH-receptor autoantibody; TSH = thyroidstimulating hormone; PTU = propylthiouracil; TID = thrice daily; UAE = United Arab Emirates; US = ultrasound INTRODUCTION Graves disease (GD) is one of the most common causes of hyperthyroidism (1). Untreated, GD may lead to serious adverse events like atrial fibrillation and heavily affect the patient’s quality of life (1). Contemporary management of GD relies on either the use of antithyroid drug (ATD)
ENDOCRINE PRACTICE Vol 23 No. 3 March 2017 299
300 Graves Disease in the MENA Region, Endocr Pract. 2017;23(No. 3)
therapy, thyroidectomy or radioactive iodine (RAI) (2-4). GD management has been influenced by a number of clinical advances pertaining to the recognition of impact of RAI therapy on Graves orbitopathy (GO), concerns on adverse effects of propylthiouracil (PTU), and recent trends to optimize management goals for thyroid dysfunction during pregnancy (5-7). Evidence and expertise-based practice guidelines pertaining to hyperthyroidism management were published by several reputed professional associations (2-4). These guidelines are intended to positively affect change in patient management. Persistent and marked differences in GD management throughout the world have been observed (8). Clinical practice patterns in the management of GD have been monitored over the years using physician surveys in various parts of the world. The most recent 3 from North America and Europe are noteworthy as they used identical methodologies (9-11). We are not aware of any studies published hitherto specifically on the management practices in the Middle East and North Africa (MENA) region (12). To document current practices in management of GD in the MENA region and to compare these with practices elsewhere, we surveyed a large pool of practicing physicians with an analogous questionnaire to those used in previous studies (9-11). METHODS This study was conducted by a group of endocrinologists practicing in the MENA region wishing to examine the patterns of clinical practice in management of GD. We aimed to (1) document physicians’ perceptions and practices, (2) ascertain available resources for management, and (3) examine the homogeneity of the views and practices of physicians dealing with thyroid disease. This firstever survey should provide a baseline dataset to help direct guidelines, education, and further research and monitor trends in the future. A web-based commercial survey management service (Survey Monkey, Palo Alto, CA) was used in a similar fashion to the previously published surveys. The questionnaire itself was identical to the one used before (10). The index case (a 42-year-old female with uncomplicated GD was the same as in the previous 2 surveys (9,10) with 2 variants, including a patient with associated GO and a patient anticipating pregnancy over the next 6 to 12 months. The survey was provided in its original English. In the absence of a single MENA regional endocrine society with a membership list that can define a study population, several questions were added to define the professional profiles of the respondents and their practices. The target population was identified from a list of electronic mail addresses pooled from continuous professional development delegates, speakers, authors or members of various groups, or forums in various parts of the MENA
Copyright © 2017 AACE
region. They all received an initial e-mail that explained the rationale and what was required from the respondents, followed by 4 reminder e-mails over a 12-week period including unique e-mail-specific electronic links to the questionnaire. All subjects provided an explicit informed consent electronically to participate before they could proceed to the survey questions. At the end of the study, survey responses were collected anonymously, stored electronically, and analyzed. Summary statistics were prepared for responses to each question. Because not every participant answered all questions, the percentage of respondents providing a given answer was calculated individually for each question, using the number of respondents to that question in the denominator. Furthermore, results from an appropriate subset (viz. endocrinologists) were compared with those of the latest American, European, and Italian surveys (9-11). RESULTS Respondents’ Profiles Only respondents practicing in the MENA region were included in the analysis. A total of 352 respondents confirmed eligibility and willingness to participate in the study. They were 128 (36.6%) adult endocrinologists, 64 (18.5%) primary care physicians, 57 (16.3%) physicians in general internal medicine, 52 (14.9%) general internal physicians with special interest and practice of endocrinology, 24 (6.9%) pediatric endocrinologists, 13 (3.7%) surgeons, 8 (2.3%) obstetrician/gynecologists, and 4 (1.1%) nuclear medicine physicians. Overall, 169 (48.4%) graduated over 20 years earlier, 127 (36.4%) graduated between 10 and 20 years earlier, and 53 (15.4%) respondents graduated less than 10 years ago. Professional grades were mostly 177 (50.9%) consultant (i.e., attending) physicians, 108 (31.0%) specialists/fellows, 21 (6.1%) residents in training, and 42 (12.1%) in other unspecified grades. The most frequently represented countries were the United Arab Emirates (UAE) (120), Pakistan (21), Iraq (21), and Saudi Arabia (20). 344 respondents described nonmutually exclusive affiliation with international, regional, or national endocrine associations (excluding those mainly interested in diabetes). Affiliation with the American Association of Clinical Endocrinologists (AACE) was stated by 53%, regional societies of endocrinology and thyroid disease by 46%, The Endocrine Society (U.S.) by 26%, and to lesser extents with the European Society of Endocrinology (17%), American Thyroid Association (ATA, 9%), Society for Endocrinology (United Kingdom, 7%), and European Thyroid Association (2%). Access to resources was confirmed by 351 respondents as follows: measurements of thyroid hormones (97%), thyroid ultrasound (US) imaging (88%), ATD therapy (87%), measurement of thyroid antibodies (83%), fine-needle aspiration and cytologic examination (72%), a thyroid surgeon
Copyright © 2017 AACE
Graves Disease in the MENA Region, Endocr Pract. 2017;23(No. 3) 301
(64%), an ophthalmologist with expertise in thyroid disease (62%), and nuclear medicine scanning facilities (53%). No data were collected on nonrespondents.
first-line treatment preferred by 53%, while RAI treatment was selected by 37%, b-blockers alone by 6%, and thyroidectomy by 3%.
Diagnostic Evaluation of the Index Case Serum TSH and free thyroxine (FT4) assays would be the most requested measurements (83% and 80%, respectively), whereas serum free tri-iodothyronine (FT3) or total T3 would be less frequently ordered (62% and 13%, respectively). In the initial assessment, serum antithyroid peroxidase antibody (TPOAb) and thyroid-stimulating immunoglobulins would be ordered by a greater proportion of respondents (50% and 46%, respectively), whereas serum antithyroglobulin antibodies would be ordered by fewer respondents (36%). Thyroid US would be requested by almost two-thirds of respondents (64%), while only a minority would order nuclear medicine thyroid scans (33% for 99Tc, 7% for 123I) and/or RAI uptake (RAIU) (15% for 131I and 7% for 123I). Complete blood count, liver function testing, and calcium measurement would be requested by 61%, 40%, and 36%, respectively (Fig. 1).
ATD Treatment Carbimazole (CBZ) was the preferred ATD by 86% of respondents, methimazole (MMI) by 9%, and PTU by 5%. When using CBZ, most respondents (27%) used a daily starting dose of 30 mg daily, while 15% started with 40 mg daily, and 11% with 10 mg. When using PTU, most respondents (30%) starting with 100 mg thrice daily (TID), while 16% started with 50 mg TID, 11% used 150 mg TID, and 9% with 100 mg twice daily (BID). The titration method was selected by 70% of respondents, while the block-and-replace method was used by 8% routinely and by 23% in selected cases. After instituting ATD therapy, the initial evaluation of serum thyroid hormone levels would be performed after 4 and 6 weeks by 44% and 29% of respondents, respectively. Furthermore, after restoring euthyroidism, thyroid function tests would be performed every 3 months by 57% of the respondents and every 2 months by 29% of respondents, though some (9%) would repeat them more often at monthly intervals. Other than thyroid hormone levels, 26% of respondents would not perform any routine monitoring, whereas 53% and 21% of the respondents would monitor complete blood counts and serum levels of liver-associated enzymes. In the event of the occurrence of a pruritic macular rash that failed to respond to antihistamines, 60% of respondents would switch to another ATD, 29% would select an alternative
Treatment of Uncomplicated GD (Index Case) Preferred First-Line Treatment b-adrenergic blocking drugs (most frequently propranolol, 86%) would initially be used definitely or possibly by the large majority of respondents (71% and 25%, respectively). Target heart rates on b-blockers of
