The High Prevalence of Thyroid Goiter among Arab Minorities in Israel - A Possible Hereditary Connection

Background: Thyroid goiter is endemic in certain world areas, especially with low Iodine supply. Genetic predisposition with the combination of various environmental factors have been suggested as risk factors for thyroid goiter. The exact mechanism causing thyroid goiter is still not clear. Israel has a small geographic area with a diverse non mixed ethnic minorities. All populations share similar environmental conditions. The possibility of an ethnic predisposition for thyroid goiter development in these ethnic populations is yet to be studied.

Methods: All adult patient with thyroid goiter presented to the head and neck clinic between 2019-2021 were included in the study. Patient files were reviewed retrospectively for demographic data and goiter related symptoms. The overall incidence rate of goiter for each group was calculated.

Results: A total of 392 patients were included in the study, 235 were Jewish, 123 Arab Druze and 34 Arab Muslims. The overall incidence of thyroid goiter in the Arab Druze group was 6.92% (CI 5.75 - 8.25) compared to 4.11% in the Jewish (CI 3.60 - 4.67) group and 7.21% (CI 4.99 - 10.08) in the Muslim group (34 patients only). The observed number of patients having goiter in comparison with the expected value of Goiter and the Standardized Incidence Ratio (SIR) for the Arab Druze population was 1.41 (1.18 - 1.67) in comparison to the Jewish population -0.84 (0.73 - 0.95).

Conclusions: Thyroid goiter prevalence in the Arab Druze population was higher compared to the Jewish population with similar environmental conditions. Further studies of possible ethnic genetic influences on goiter development are warranted. A larger study of goiter prevalence in the Arab Muslims group should be considered.

TG: Thyroid Goiter; TSH: Thyroid Stimulating Hormone; FNS: Fine-Needle Aspiration; ATA: American Thyroid Association; FNAC: Fine-Needle Aspiration Cytology

Thyroid Goiter (TG) is a benign hyperplasia of the thyroid gland. It is classified either as diffuse - with an overall enlargement of the thyroid, or nodular - an irregular cell growth that forms nodules. [1]. TG affects approximately 7% of the worldwide general population, being more common in the women population [2,3]. The clinical presenting symptoms associated with TG depends on goiter size and location [4,5]. The majority of TG are asymptomatic, and are usually detected in a routine physical examination of the neck area [6-8].

TG is considered endemic in certain world areas. Iodine deficiency- usually associated with poor water supply, is considered as the main factor [9,10]. In recent years, various populations studies of TG in endemic areas have suggested that the differences in TG prevalence in between populations cannot be attributed to Iodine deficiency alone [1]. Thus the possibility of an existing genetic predisposition combined with environmental factors has been suggested as the main root cause for high TG prevalence [11,12].

Various studies have been published supporting this theory: A twin study from Denmark [12], concluded that the heritability of the predisposition to develop goiters can be accounted for 82% of cases, with only 18% that can be explained by environmental factors [12]. Another study from Denmark has found a greater overlap of thyroid volume in twins which was attributed to genetic factors [13]. A study by Teumer A, et al. [14] from 2011 has found 4 genetic loci that were associated with thyroid volume [14,15]. A genomic research of a Canadian family with high goiter incidence, has identified a locus on chromosome 14q that can be a possible cause for goiter [16]. Targovnik HM, et al. [17] identified 50 mutations linked with goiter and hypothyroidism or euthyroidism that confirms the allelic heterogeneity of the thyroid gene mutations. Hegedüs, et al [18] have concluded that the influence of heritability or of a shared genes pool in TG development is markedly increased with the non-presence of environmental factors as in shared environments and similar living habitats. All of these studies suggest the possibility of hereditary or a genetic predisposition as the major factor contributing for TG prevalence, regardless of the environmental factors [19].

The possibility of an ethnic hereditary, an ethnic group genetic predisposition, being a major factor for TG prevalence in endemic populations has almost not been studied. Two previous studies of different population exist: a study of the Efe Pygmies from Zaire in 1989 [20], and a study of Ethiopian origin immigrants in Israel from 1993 [21]. These two similar studies of different populations and geographic locations, have found a markedly high TG prevalence in each of the study groups in comparison to other populations residing in the same geographic areas. Both studies have concluded an ethnic hereditary rather than dietary or environmental factors is the major cause of the high TG prevalence in the studied populations.

A high incidence of goiter has been reported [22] in the Druze population of the northern Golan Heights in Israel during the late 1960s [23]. This was attributed at time to the low iodine content of drinking water 2 - 2.5 μg/l. During the 1980s and 1990s of the past century, there have been further reports of endemic goiter in that area. This was attributed to the establishment of integrated regional water-supply systems and to the operation of the National Water Carrier Network distributing water with an I-content of 14 μg/l [22].

The population of Israel is unique in its diverse ethnic composition: Jews, Arab Muslims, Arab Christians and Arab Druze. These ethnic groups are not mixed for religious, historical and cultural reasons. The Arab Druze are an isolated community from religious reasons, which resides partly in Lebanon, Syria and Israel [24]. The Arab Druze strictly close their religion to new adherents. Druze customs strongly favor intermarriage, thus preventing possible mixture with all other ethnic groups in their surroundings [25]. The prevalence of TG and the possibility of ethnic hereditary in this ethnic group has yet to be studied.

A retrospective study. All adult patient's files presented with goiter to the head and neck clinic between 2019-2021 were reviewed. To limit possible influences of environmental factors among groups, only patients who reside in the same geographical area with similar water and food supply were included. The Druze group included patients from the 4 villages: Ein K, Masade B and Majdal S. Jewish patients included were from Hatzor H, Kiryat S, Safed and Katzrin. The Muslim Arab group included patients from Tuba-Zangariya village. All locations are a non- mixed single ethnic group residency (Druze, Jewish or Arab-Muslim respectively). The water sources supplying all these locations were comparable in terms of quality and Iodine levels (4-6 μg/L) as reported by the national Israel water authority.

Patient data collection

Patient data collected included: goiter type, Bethesda score of Fine Needle Aspiration Cytopathology (FNAC), goiter related symptoms, ethnicity, place of residence, age, gender and family history.

Demographic data collection

Demographic data of all included locations – the number of adult persons living in each location, was obtained from the Israel Population & Immigration Authority.

In our analysis, continuous data are described using means and standard deviations. Categorical data are described using frequencies and percentages. The comparison of numeric data between groups was performed by an independent sample t test. Relationships between categorical variables and sample groups were examined using Chi-square test or Fisher's exact test depending on the sample size. Standardized Incidence Ratio higher than 1 was considered higher than expected and a p - value lower than 5% was considered statistically significant. The data were analyzed using the SPSS software, version 25 (SPSS Inc., Chicago, IL, USA).

A total of 674 Goiter patients' files were reviewed for their demographic data and other goiter related clinical characteristics. 392 patients met the inclusion criteria and were included in the final analysis (Table 1). Among the included files 235 were Jewish, 123 Druze and 34 Muslims. The total overall mean age was 57.9, with 82.7% of the patients were females (p - value 0.562). The most common type of goiter was MNG type - nontoxic with 54.6% (p – value -0.324). With the second most common being nodular nontoxic goiter with 40.1 (p - value 0.714). Family history was highest among Muslim patients 17.6 (p - value 0.006). Other variables are presented in table 1. The overall incidence rate of goiter cases divided by their respective population (Residents over the age of 18) x1000 is presented in table 2. The overall incidence of thyroid goiter in the Arab Druze group was 6.92% (CI 5.75 - 8.25) compared to 4.11% in the Jewish (CI 3.60 - 4.67) group and 7.21% (CI 4.99 - 10.08) in the Muslim group (34 patients only). The observed number of patients having goiter in comparison with the expected value of Goiter and the Standardized Incidence Ratio (SIR) for each group is presented in table 3. A substantial increased in the prevalence of Goiter in the Arab Druze population was observed, with a Standardized Incidence Ratio (SIR) value of 1.41 (1.18 - 1.67) in comparison to the Jewish population -0.84 (0.73 - 0.95).

This is the first study of goiter prevalence in adult Arab origin populations. Our results show a significantly higher prevalence of TG in the Arab Druze population in comparison to the Jewish population, with similar environmental conditions. Our results could suggest a possible ethnic hereditary predisposition for TG development in the Arab Druze population.

TG is considered as caused by genetic factors interacting with physical and environmental conditions (e.g.: low iodine intake, cigarette smoking, obesity and gender) [26]. Multiple previous studies have demonstrated that in areas with adequate iodine intake, a familial genetic predisposition is the major factor for TG development, regardless of the environmental conditions [27]. It has already been shown that there is a disproportionate under-recognition on the impact of ethnic hereditary on various health conditions amongst racial and ethnic minorities worldwide [28]. The term Ethnic hereditary describes the genetic pooling of a specific ethnic group. An ethnic hereditary predisposition is made possible in small closed societies – either from geographic or ethnic reasons, where the custom of intermarriage is common [29]. The Arab Druze population in Israel was estimated at 150,000 persons in 2021 [30] and is distributed mainly in the northern part of Israel (Less than 100 sqkm). Druze customs strongly favor marriage within the same village or the same geographical area. This social structure has turned the Druze into a population which remains genetically isolated from their surrounding neighbouring communities [31]. A previous study of the phylogenetic mitochondrial haplogroup of the Arab Druze in Israel has demonstrated that they are genetically a population isolate [25,32]. Two previous studies support this theory: Schaffer M, et al. [33] have found an unusually high prevalence of classical Kaposi’s sarcoma in the Arab Druze from Israel, while Atzmon I, et al. [34] have observed lower cancer rates among Arab Druze in comparison to the non-Druze Arab and Jewish populations in Israel. Thus the possibility of an existing ethnic hereditary predisposition for TG in this unique population is highly possible.

All the populations included in this study live in the same geographical area (Approx. 50 sqkm), with similar environmental conditions. The water sources supplying all the included populations’ residencies are of similar nature, with average Iodine levels of 4-6 μg/L. The possible effect of specific goiterogenic foods effecting goiter development in the study groups can also be excluded. The Arab Druze in Israel leads a modern life style in terms of technology use and academic education. In a survey from 2020 of the general Israeli population, no significant differences were found between Arabs - Muslims or Druze and Jewish families in regard to healthy foods consumption or nutritional habits [35]. The survey also found that the dietary habits of all populations are similar in terms of vegetable and meat consumption. The Jews, Druze and Muslims all refrain from pig meat consumption from religious reasons. A previous similar study on the Israeli Ethiopian origin population from 1993, have shown high TG prevalence regardless if the patients maintained either a modern Israeli diet or the traditional Ethiopian diet [36].

The early detection of TG is of high importance. An enlargement of goiter can result in symptoms related to tracheal or esophageal compression (Dyspnea and/or dysphagia). Early detection and proper treatment can prevent possible complication such as progressive enlargement or mediastinal extension (tracheal narrowing, superior vena cava syndrome). Cosmetic discomfort resulting from an enlarged goiter, especially in female patients is of no less importance. Early detection can allow prompt surgery while goiter size is still small [6]. Delayed surgical treatment can result in possible surgical complication such as damage to the recurrent laryngeal nerve or hypocalcemia due to a larger goiter size. Our results can point to the benefit of promoting early thyroid screening in the Druze community, especially in women.

We also found a high prevalence of TG in the Muslim population group (SIR 1.44, CI 1.02 - 2.00). These findings are in line with two studies from Jordan presenting high prevalence of thyroid dysfunction and TG in the Jordanian Arab population [37,38]. The Arab Muslim group in our study was relatively small and included only 34 patients (8.7%). This low sample size can affect SIR value, and doesn't allow a clear conclusion. Still, these findings are of interest and call for further investigation.

The Arab Druze population in Israel has higher TG prevalence in comparison to the Jewish population with similar environmental conditions. Early thyroid screening in the Druze community especially in women should be considered. Further studies of possible genetic factors are warranted. A larger study of goiter prevalence in the Israeli Arab Muslims should also be considered.

1. Knobel M. Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters. J Endocrinol Invest. 2016 Apr;39(4):357-73. doi: 10.1007/s40618-015-0391-7. Epub 2015 Sep 21. PMID: 26392367.
2. Maniakas A, Davies L, Zafereo ME. Thyroid Disease around the World. Otolaryngol Clin North Am. 2018 Jun;51(3):631-642. doi: 10.1016/j.otc.2018.01.014. Epub 2018 Mar 13. PMID: 29548512.
3. Vander JB, Gaston EA, Dawber TR. The significance of nontoxic thyroid nodules. Final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med. 1968 Sep;69(3):537-40. doi: 10.7326/0003-4819-69-3-537. PMID: 5673172.
4. Pankow BG, Michalak J, McGee MK. Adult human thyroid weight. Health Phys. 1985 Dec;49(6):1097-103. doi: 10.1097/00004032-198512000-00005. PMID: 4077513.
5. Maravall FJ, Gómez-Arnáiz N, Gumá A, Abós R, Soler J, Gómez JM. Reference values of thyroid volume in a healthy, non-iodine-deficient Spanish population. Horm Metab Res. 2004 Sep;36(9):645-9. doi: 10.1055/s-2004-825901. PMID: 15486817.
6. Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021 Oct;161(4):1325-1332.e7. doi: 10.1053/j.gastro.2021.06.078. Epub 2021 Aug 26. PMID: 34454714; PMCID: PMC8740554.
7. Mariani G, Tonacchera M, Grosso M, Fiore E, Falcetta P, Montanelli L, Bagattini B, Vitti P, Strauss HW. The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 2: Nodular Goiter, Hypothyroidism, and Subacute Thyroiditis. J Nucl Med. 2021 Jul 1;62(7):886-895. doi: 10.2967/jnumed.120.251504. Epub 2021 Feb 12. PMID: 33579801.
8. Bartsch DK, Luster M, Buhr HJ, Lorenz D, Germer CT, Goretzki PE; German Society for General and Visceral Surgery. Indications for the Surgical Management of Benign Goiter in Adults. Dtsch Arztebl Int. 2018 Jan 8;115(1-02):1-7. doi: 10.3238/arztebl.2018.0001. Erratum in: Dtsch Arztebl Int. 2018 Mar;115(9):144. doi: 10.3238/arztebl.2018.0144. PMID: 29345225; PMCID: PMC5778395.
9. Malboosbaf R, Hosseinpanah F, Mojarrad M, Jambarsang S, Azizi F. Relationship between goiter and gender: a systematic review and meta-analysis. Endocrine. 2013 Jun;43(3):539-47. doi: 10.1007/s12020-012-9831-8. Epub 2012 Dec 14. PMID: 23238875.
10. Jiang H, Tian Y, Yan W, Kong Y, Wang H, Wang A, Dou J, Liang P, Mu Y. The Prevalence of Thyroid Nodules and an Analysis of Related Lifestyle Factors in Beijing Communities. Int J Environ Res Public Health. 2016 Apr 22;13(4):442. doi: 10.3390/ijerph13040442. PMID: 27110805; PMCID: PMC4847104.
11. Carlé A, Krejbjerg A, Laurberg P. Epidemiology of nodular goitre. Influence of iodine intake. Best Pract Res Clin Endocrinol Metab. 2014 Aug;28(4):465-79. doi: 10.1016/j.beem.2014.01.001. Epub 2014 Jan 10. PMID: 25047199.
12. Brix TH, Kyvik KO, Hegedüs L. Major role of genes in the etiology of simple goiter in females: a population-based twin study. J Clin Endocrinol Metab. 1999 Sep;84(9):3071-5. doi: 10.1210/jcem.84.9.5958. PMID: 10487667.
13. Hansen PS, Brix TH, Bennedbaek FN, Bonnema SJ, Kyvik KO, Hegedüs L. Genetic and environmental causes of individual differences in thyroid size: a study of healthy Danish twins. J Clin Endocrinol Metab. 2004 May;89(5):2071-7. doi: 10.1210/jc.2003-031999. PMID: 15126523.
14. Teumer A, Rawal R, Homuth G, Ernst F, Heier M, Evert M, Dombrowski F, Völker U, Nauck M, Radke D, Ittermann T, Biffar R, Döring A, Gieger C, Klopp N, Wichmann HE, Wallaschofski H, Meisinger C, Völzke H. Genome-wide association study identifies four genetic loci associated with thyroid volume and goiter risk. Am J Hum Genet. 2011 May 13;88(5):664-73. doi: 10.1016/j.ajhg.2011.04.015. PMID: 21565293; PMCID: PMC3146733.
15. Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: the basis for understanding thyroid function and nodular goiter growth. Endocr Rev. 1989 May;10(2):125-35. doi: 10.1210/edrv-10-2-125. PMID: 2666115.
16. Bignell GR, Canzian F, Shayeghi M, Stark M, Shugart YY, Biggs P, Mangion J, Hamoudi R, Rosenblatt J, Buu P, Sun S, Stoffer SS, Goldgar DE, Romeo G, Houlston RS, Narod SA, Stratton MR, Foulkes WD. Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer. Am J Hum Genet. 1997 Nov;61(5):1123-30. doi: 10.1086/301610. PMID: 9345104; PMCID: PMC1716029.
17. Targovnik HM, Esperante SA, Rivolta CM. Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations. Mol Cell Endocrinol. 2010 Jun 30;322(1-2):44-55. doi: 10.1016/j.mce.2010.01.009. Epub 2010 Jan 20. PMID: 20093166.
18. Hegedüs L, Brix TH, Paschke R. Etiology of simple goiter. Thyroid. 2009 Mar;19(3):209-11. doi: 10.1089/thy.2009.0047. PMID: 19265491.
19. Knudsen N, Brix TH. Genetic and non-iodine-related factors in the aetiology of nodular goitre. Best Pract Res Clin Endocrinol Metab. 2014 Aug;28(4):495-506. doi: 10.1016/j.beem.2014.02.005. Epub 2014 Mar 6. PMID: 25047201.
20. Dormitzer PR, Ellison PT, Bode HH. Anomalously low endemic goiter prevalence among Efe pygmies. Am J Phys Anthropol. 1989 Apr;78(4):527-31. doi: 10.1002/ajpa.1330780408. PMID: 2785346.
21. Luboshitzky R, Dharan M, Qupty G, Dgani Y, Atar S, Flatau E. Endemic goiter in Ethiopian Jews--possible pathogenetic factors. Isr J Med Sci. 1993 Jun-Jul;29(6-7):368-70. PMID: 8349452.
22. Rosenthal E, Mates A‏. Iodine concentrations in groundwater of northern Israel and thier relation to the occurrence of goiter. Applied Geochemistry. 1986;1:591-600.
23. Rosenthal E, Mates A‏. Iodine concentrations in groundwater of northern Israel and thier relation to the occurrence of goiter. Applied Geochemistry. 1986.
24. Yehya NA, Dutta MJ. Health, religion, and meaning: a culture-centered study of Druze women. Qual Health Res. 2010 Jun;20(6):845-58. doi: 10.1177/1049732310362400. Epub 2010 Feb 24. PMID: 20181823.
25. Vardi-Saliternik R, Friedlander Y, Cohen T. Consanguinity in a population sample of Israeli Muslim Arabs, Christian Arabs and Druze. Ann Hum Biol. 2002 Jul-Aug;29(4):422-31. doi: 10.1080/03014460110100928. PMID: 12160475.
26. Neumann S, Bayer Y, Reske A, Tajtáková M, Langer P, Paschke R. Further indications for genetic heterogeneity of euthyroid familial goiter. J Mol Med (Berl). 2003 Nov;81(11):736-45. doi: 10.1007/s00109-003-0463-6. Epub 2003 Oct 15. PMID: 14564411.
27. Molinaro A, Orlandi P, Niccolai F, Agretti P, De Marco G, Ferrarini E, Di Cosmo C, Vitti P, Piaggi P, Di Desidero T, Bocci G, Tonacchera M. Genetic interaction analysis of VEGF-A rs3025039 and VEGFR-2 rs2071559 identifies a genetic profile at higher risk to develop nodular goiter. J Endocrinol Invest. 2020 Feb;43(2):149-155. doi: 10.1007/s40618-019-01092-9. Epub 2019 Aug 2. PMID: 31376092.
28. Ahsan MD, Webster EM, Nguyen NT, Qazi M, Levi SR, Diamond LC, Sharaf RN, Frey MK. Underrepresentation of racial and ethnic minorities in cascade testing for hereditary cancer syndromes. Eur J Hum Genet. 2023 Jul;31(7):723-724. doi: 10.1038/s41431-023-01364-2. Epub 2023 Apr 28. PMID: 37117326; PMCID: PMC10325970.
29. Singer J, Eszlinger M, Wicht J, Paschke R. Evidence for a more pronounced effect of genetic predisposition than environmental factors on goitrogenesis by a case control study in an area with low normal iodine supply. Horm Metab Res. 2011 May;43(5):349-54. doi: 10.1055/s-0031-1273699. Epub 2011 Mar 16. PMID: 21412689.
30. Statistics. Israel center bureaue of the druze population of Israel. 2024.
31. Zlotogora J. The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel. Hum Genet. 2010 Nov;128(5):473-9. doi: 10.1007/s00439-010-0890-8. Epub 2010 Sep 18. PMID: 20852892.
32. Slush LI, Skorecki K. The druze: A population genetic refugium of the near east. PLoS One. 2010;3:e2105.
33. Schaffer M, Kassem R, Ben Shlomo I, Livoff A, Asna N, Zidan J. Unusually high prevalence of classical Kaposi's sarcoma in Druze Muslims of Northern Israel. J Eur Acad Dermatol Venereol. 2018 Feb;32(2):e80-e81. doi: 10.1111/jdv.14535. Epub 2017 Sep 14. PMID: 28833522.
34. Atzmon I, Linn S, Portnov BA, Richter E, Keinan-Boker L. Lower Cancer Rates Among Druze Compared to Arab and Jewish Populations in Israel, 1999-2009. J Relig Health. 2017 Jun;56(3):741-754. doi: 10.1007/s10943-014-9973-5. PMID: 25516295.
35. Myers JDC. Food consumption habits and attitudes to the nutrition labelling program. Brookdale Institute JDC, Jerusalem.
36. Luboshitzky R, Dharan M, Qupty G, Dgani Y, Atar S, Flatau E. Endemic goiter in Ethiopian Jews--possible pathogenetic factors. Isr J Med Sci. 1993 Jun-Jul;29(6-7):368-70. PMID: 8349452.
37. Kharabsheh S, Belbesi A, Qarqash W, Azizi F. Goiter prevalence and urinary iodine excretion in schoolchildren of Jordan. Int J Vitam Nutr Res. 2004 Jul;74(4):301-4. doi: 10.1024/0300-9831.74.4.301. PMID: 15580813.
38. Abu-Helalah M, Alshraideh HA, Al-Sarayreh SA, Al Shawabkeh AHK, Nesheiwat A, Younes N, Al-Hader A. A Cross-Sectional Study to Assess the Prevalence of Adult Thyroid Dysfunction Disorders in Jordan. Thyroid. 2019 Aug;29(8):1052-1059. doi: 10.1089/thy.2018.0579. Epub 2019 Jul 1. PMID: 31146635.