Abstract
Objective:
Arctic living is influenced by cold winters, short summers, and excessive iodine intake from the traditional Inuit diet providing for habitation of the Arctic for centuries. This is changing and we surveyed thyroid function in populations living in Greenland.
Design:
Population-based cross-sectional study.
Methods:
Data were collected in the capital city in West Greenland and in rural East Greenland. Information on lifestyle, dietary habits, and medical history was obtained using questionnaires. Thyrotropin, free thyroxine, free triiodothyronine, thyroglobulin, and thyroglobulin antibody were measured in serum, iodine, and creatinine in spot urine samples.
Results:
One percent of the Greenlandic population was invited and 535 participated with an overall participation rate of 95%. Iodine excretion was 225 μg/24 hours in East Greenland and 169 μg/24 hours among West Greenland Inuit. Hyperthyroidism occurred in 10.7% of West Greenlandic Inuit (men/women: 4.3%/16.3%) and 7.8% of East Greenlandic Inuit (3.8%/12.8%). Hypothyroidism was found in 2.7% in West Greenland (0.0%/5.0%) and 5.6% (5.6%/5.6%) in East Greenland.
Conclusion:
Hyperthyroidism was frequent among Inuit and the occurrence of hypothyroidism was low. The pattern of hyper- and hypothyroidism among Greenlandic Inuit with adequate iodine intake was comparable with those seen in populations with iodine deficiency. Inuit may thus have adapted to excessive iodine intake over centuries, causing a need for a higher iodine intake to prevent iodine deficiency disorders.
Introduction
Inuit have inhabited the Arctic regions in Alaska, Canada, Greenland, and Siberia for centuries. Life in the Arctic is characterized by cold winters and short summers with mean temperatures below 10°C. In addition, the distinct traditional Inuit diet consists of marine food items. Both factors may influence thyroid function.
Cold adaptation involves thyroid hormone metabolism (1,2) and chronic cold adaptation associates with thyroid hyperactivity (3). Moreover, Greenlandic Inuit have adapted to the extreme living conditions by selection of genes promoting heat-producing brown fat cells and for coping with a high-fat marine diet (4). Yet, an influence on the occurrence of thyroid disease remains unsettled.
The traditional Inuit diet is dominated by marine food items rich in iodine (5). This causes an iodine intake that ranged from high within the range recommended by the WHO (6) to mild iodine deficiency depending on the intake of a westernized diet (7). We hypothesized that Greenlandic Inuit have adapted to the excessive iodine intake caused by the dependency on the iodine-rich traditional marine diet, which could influence the occurrence of thyroid diseases among present-day Inuit (8,9).
This led us to survey populations in two areas in Greenland with different dietary habits and different levels of iodine intake (7) to describe thyroid function in relation to iodine nutrition in populations in Greenland, and to assess the prevalence of thyroid dysfunction.
Subjects and Methods
This study of thyroid function and screening for dysfunction was conducted among inhabitants in two distinctly different areas in Greenland.
Area of investigations
Nuuk is the capital city of Greenland and is situated on the west coast of Greenland (64.15N 51.35W). It had 12.909 inhabitants at the time of investigation, in which 20% were non-Inuit. Nuuk is a metropolitan city with restaurants, cafés, and various types of stores, including convenient stores selling imported foods mainly from Denmark and a local market selling traditional foods. The lifestyle in Nuuk is more westernized than the rest of the country.
The Ammassalik District is located in the remote East Greenland. The area was isolated until 1884 and is still difficult to access as it is only accessible by plane. It is sparsely populated with around 3000 inhabitants (95% Inuit) spread over an area of 243,000 km2. Tasiilaq is the main city and has a café and a couple of small convenient stores. The groceries are shipped to the main city in the summer and the supplies by plane are limited to few vegetables. There are seven settlements in Ammassalik District, and each has a store with scarce selection of imported foods. Hunting is the main occupation and leisure time activity, and living in East Greenland in general comes with cold exposure (3).
Subjects
Participants were 50 to 69 years of age, Inuit and non-Inuit. The age group was selected to obtain a valid representation of a population in different steps in the transition from a traditional way of living to a more westernized lifestyle. Nuuk in West Greenland and Ammassalik District in East Greenland were selected for investigation to obtain the widest representation of the Greenlandic population. In Ammassalik District, the town Tasiilaq and the settlements Tiniteqilaaq, Sermiligaaq, Kulusuk, and Kuummiut were included, and settlements with less than 15 inhabitants were excluded for practical reasons. In Nuuk, the hospital registration system was used to obtain names and addresses, and 480 individuals in the age group 50 to 69 years were randomly selected. The East cohort was obtained from the National Civil Registration System in which every person living in Greenland, Faroe Islands, and Denmark is registered. All the 50- to 69-year olds in Ammassalik District were invited to participate in the study (n = 336).
A participant was classified as Greenlander (Inuk) if the person was born in Greenland and had both parents born in Greenland. All other participants were classified as non-Inuit.
The Commission for Scientific Research in Greenland approved this study before the onset (reference no. 505-31). All subjects signed the informed consent form in the participant's chosen language (Greenlandic or Danish).
Investigational procedures
The local hospital porter or the nursing station attendant delivered a letter of invitation (in Greenlandic and Danish) to each subject. Nonresponders were invited three times before being registered as nonattenders. The investigation took place at the local health care facility or, by request, at home visits. An interpreter or one of the investigating physicians interviewed the participants. Questions were asked as written in the questionnaires. Information on lifestyle, dietary habits, and medical history was obtained using the questionnaires, including thyroid-related questions. The question on thyroid disease was: “has a doctor told you that you had thyroid dysfunction,” and if the answer was yes, a subsequent question on treatment was asked. The investigating physicians performed a physical examination, including height without shoes, weight in indoor clothing, major disabilities, and examination of the neck for visible goiter.
Sample collection and assays
A nonfasting spot urine sample was collected in iodine-free polyethylene containers from all the 535 participants at the visit, and blood samples drawn using minimal tourniquet. Serum was separated and samples were stored at −20°C until analysis.
The iodine content in urine was determined by the Sandell–Kolthoff reaction modified after Wilson and van Zyl (10) as described in detail previously (11,12). Urinary creatinine was determined by the kinetic Jaffé method (13). Urinary iodine concentration varies with hydration and urine volume, and we thus adjusted excretion for dilution by calculating the iodine:creatinine ratio (7,14), and this correction was done using the ethnic specific creatinine excretion (15).
Serum thyroglobulin (TG) is a marker of thyroid activity and abnormalities such as goiter and thyroid nodules (3,16,17), and TG, thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were measured using LUMItest (BRAHMS, Berlin, Germany). The functional sensitivity of the TSH assay was 0.1 mU/L. Reference intervals were 0.3–4.5 mU/L for TSH, 9.8–20.4 pmol/L for fT4, and 3.6–6.9 pmol/L for fT3. The TG assay had a working range from 1 to 500 μg/L, and median values of around 9, 10, and 15 μg/L are seen in iodine-replete, mild, and moderately deficient Caucasian Danes, respectively (16,17). TG antibodies (TGAbs) were measured using DYNOtest RIA (BRAH-MS Diagnostica) with a functional sensitivity of 20 kU/L for TGAb (18). Individuals with TGAbs above 100 kU/L (n = 39) were excluded from calculations including serum TG, as TGAbs above this level influence measurements of TG. All assay runs included samples from different groups investigated in random order.
Statistical analysis
Results are given as median with 25th and 75th percentiles. Groups were compared using nonparametric statistics: chi-squared test for comparison of proportions, Mann–Whitney U test for comparison of two groups, and Kruskal–Wallis test for comparing several groups. Distributions were tested using the Kolmogorov–Smirnov test, and logarithmic transformation was performed on data not following the Gaussian distribution for further analysis. Explanatory variables entered in linear regression models were sex, age, smoking habits (present, past, or never smoker), and alcohol intake (daily, occasionally, or rarely) with ethnicity entered as dependent variable when including all participants. East versus West Greenland Inuit were entered as a dependent variable when including only Inuit. Finally, ethnicity, age, smoking habit, and alcohol intake were entered as explanatory variables with sex as the dependent variable.
A p-value of <0.05 was considered significant. Data were processed and analyzed using Corel Quattro Pro 8 (Corel Corporation, Ottawa, Ontario, Canada) and the Statistical Package for the Social Sciences version 13.0 (SPSS, Inc., Chicago, IL).
Results
Population
One percent of the Greenlandic population was invited (n = 561). In Nuuk, a random selection of 225 inhabitants in the age group 50 to 69 years were invited, and 211 attended. In Ammassalik District, all the 50- to 69-year olds in Tasiilaq and the adjacent settlements were invited (n = 336). In sum, 94% attended the investigation in Tasiilaq and 99% participated in the settlements yielding a total of 535 attending and an overall participation rate of 95%.
Table 1 lists participant descriptives. Non-Inuit were mainly skilled laborers from Denmark, who tend to move back to Denmark when they reach retirement as seen in the age and sex characteristics. The diet in the rural areas was mainly traditional marine food items, and the frequency of intake decreased with increasing urbanization. The non-Inuit diet was mainly imported foods.
Descriptives of the Participants from the Capital City Nuuk in West Greenland and in Town and Settlements in Rural Ammassalik District in East Greenland as Reported in Interview-Based Questionnaires
Chi-squared test for comparing proportions between Inuit and non-Inuit.
Chi-squared test for comparing proportions between Inuit populations.
Including 94 with certain Caucasian ethnicity and 7 with mixed ethnicity.
One non-Inuit missing.
Nine missing.
ns, nonsignificant.
Self-reported thyroid diseases
Table 2 lists participants' reporting of thyroid disease. Non-Inuit reported hyperthyroidism by 2%, while 1.2% of Inuit reported a history of hyperthyroidism. Hypothyroidism was reported by 0.9% of Inuit. Previous treatment for thyroid disease was reported by 1.2%. Previous goiter was reported by 1.4% of the Inuit and 3.0% of non-Inuit (Table 2). Thyroid medication at present was reported by one on antithyroid drug and one on thyroxine.
Reported Occurrence of Thyroid Disorders Among People in the Capital City of Nuuk in West Greenland and in Town and Settlements in Rural Ammassalik District in East Greenland
Including 94 with certain Caucasian ethnicity and 7 with mixed ethnicity.
Data missing in 1 on self-reported previous goiter.
Data missing in 2.
Urinary iodine excretion
Estimated 24-hour iodine excretion was more than adequate in the population in East Greenland (228 and 224 μg/24 hours) and within the recommended range among Inuit in the urban city Nuuk (169 μg/24 hours). Non-Inuit in Greenland were in the range of mild iodine deficiency (58 μg/24 hours) (Figure 1).

Estimated 24-hour urinary iodine excretion among participants in the capital city Nuuk in West Greenland and in town and settlements in rural Ammassalik District in East Greenland.
Thyroid function
Table 3 lists the prevalence of thyroid dysfunction as evaluated from measurements of thyroid function tests. Among non-Inuit, 4.3% were hyperthyroid and 2.2% were hypothyroid. The prevalence of thyroid dysfunction was numerically higher in Inuit, but there were no statistically significant differences with ethnicity when adjusted for sex, age group, smoking, and alcohol use (p = 0.28). Hyperthyroidism was thus found in 4/38 non-Inuit/Inuit compared with the reported 2/5 non-Inuit/Inuit. Hypothyroidism was found in 2/20 non-Inuit/Inuit, while reported by 0/4. Thus, thyroid dysfunction was detected in 64, while thyroid disease was reported by 11 (17.2%).
Thyroid Function Tests, Thyroglobulin, and Thyroid Dysfunctions Among 535 Inhabitants of the Capital Nuuk in West Greenland and the Town Tasiilaq and Settlements Tiniteqilaaq, Sermiligaaq, Kuummiut, and Kulusuk in East Greenland
Race/ethnicity adjusted for sex, age group, present smoker, and daily alcohol use.
East or West Greenland Inuit adjusted for sex, age group, present smoker, and daily alcohol use.
Sex difference adjusted for race/ethnicity, age group, present smoker, and daily alcohol use.
fT3, free triiodothyronine; fT4, free thyroxine; TSH, thyrotropin; TG, thyroglobulin; UIE, 24-hour urinary iodine excretion estimated by using ethnic-specific creatinine corrections.
The frequency of hyperthyroidism may be slightly higher among Inuit in West Greenland compared with East Greenland Inuit, while the opposite accounted for hypothyroidism. However, this pattern of difference in the occurrence of thyroid dysfunction was not statistically significant (p = 0.09).
The occurrence of thyroid dysfunction was more common in women than in men (p < 0.001) after correction for ethnicity, age group, smoking, and daily alcohol use (Table 3).
Table 3 also lists TSH, fT4, fT3, and TG in serum among participants. TSH differed with sex, while not between participant groups. A difference in fT3 between Inuit in East and West Greenland and with ethnicity was also seen in TG. In addition, median TG differed with sex.
Discussion
Principal findings
This is the first study that describes thyroid function and the occurrence of thyroid dysfunction in Greenland Inuit. We found that 10.7% of the West Greenlandic Inuit had hyperthyroidism, including a difference with sex (4.3% in men and 16.3% in women). This was slightly more than in East Greenlandic Inuit, with 7.8% having hyperthyroidism (3.8% in men and 12.8% in women) (East-West, p = 0.67). Hypothyroidism was found in 2.7% of the West Greenlandic Inuit (none in men, 5.0% in women) and 5.6% of the East Greenlandic Inuit (East-West, p = 0.93). Interestingly, the pattern of hyper- and hypothyroidism among Greenlandic Inuit with adequate iodine intake was comparable with that seen in populations with iodine deficiency. In addition, 83% with thyroid dysfunction did not report having thyroid disease.
Interpretation and implication
A previous report of cases of hyperthyroidism among Greenlandic Inuit recommended systematic studies of iodine intake and thyroid disorders in Greenland (19). Hyperthyroidism was reported by Greenlandic Inuit in numbers that differ markedly from those reported in a health study of Nord-Trøndelag (HUNT) (20), which included a population with an iodine intake around the same level (21). They found biochemical hyperthyroidism in 0.07% of men and in 0.40% of women in the parallel age groups (20), which is distinctly lower than our findings among Greenlandic Inuit. Our findings also differed from those in a Chinese population study including three subpopulations with different iodine intake levels (22), namely with borderline iodine deficiency, mild iodine deficiency, and long-term iodine excess. Hyperthyroidism was more prevalent in the community with mild iodine deficiency (3.9%) than in the community with long-term iodine excess (1.1%), but yet again much lower than our findings in Greenland of hyperthyroidism among around 4% of men and 15% of women. Furthermore, a Danish study of a population with mild-to-moderate iodine deficiency found that 4.0% of men had biochemical hyperthyroidism (23), similar to the Greenlandic Inuit male population. Still, the prevalence of hyperthyroidism was clearly higher among Inuit women (12.8% and 16.3%) compared with women in the Danish study (8.3%). The high prevalence of hyperthyroidism among Inuit women with long-term adequate iodine intake is intriguing and differs from previous studies of the relationship between iodine intake and hyperthyroidism (24,25). It may be speculated that this is related to changes in dietary habits in Greenland over recent decades, where imported food items devoid of iodine have replaced iodine-rich marine foods (26). The traditional Inuit diet is based on iodine-rich marine food items (5). Thus, Inuit may have adapted to excessive iodine intake over centuries as their survival in the frigid Arctic environment depended on the intake of these marine food items (7). Such long-term excessive iodine intake may have modified iodine uptake or dampened organification of iodine. A reduced iodine uptake may occur via alterations in the sodium/iodide symporter (NIS), which transports iodine into the cell. NIS is a complex protein that spans the plasma membrane 13 times (27). The activity of NIS depends on proper protein folding, posttranslational modifications, protein trafficking, cellular polarity, and cellular organization (27). Perturbation of any posttranslational modification, folding, or transportation to the cell surface can result in a dysfunctioning symporter and reduce the uptake of iodine. Thus, a higher iodine intake level would be required to prevent iodine deficiency among Greenland Inuit. The dietary transition away from these iodine-rich food items may have lowered the iodine intake to a level that has introduced iodine deficiency disorders to the Inuit population, even at the level of sufficient iodine intake according to the WHO classification. This introduces an uncertainty on the universal applicability of these recommendations and may suggest that iodine monitoring programs should include surveys of iodine deficiency disorders.
The link between iodine intake level and the occurrence of hypothyroidism is well known. The prevalence of hypothyroidism increases with rising iodine intake level as documented in comparative surveys comparing mild with borderline iodine deficiency (23), mild iodine deficiency with the recommended iodine intake (24), and in a survey of populations that were iodine deficient, iodine replete, and had iodine excess (25). Our population had a high urinary iodine excretion of just over 200 μg/L in East Greenland and slightly below 200 μg/L in West Greenland. The iodine intake at such high levels might be underestimated by spot urine samples (28), and the iodine nutrition level may be slightly higher. Thus, a high occurrence of hypothyroidism would be expected. Interestingly, we found an occurrence of just 5.4% in Inuit women, which was distinctly lower than the reported frequency of 18% of women in Iceland (29) with a urinary iodine excretion of around 300 μg/L, and 18% of women with a urinary iodine excretion of 150 μg/L (24). The frequency of hypothyroidism was even lower than the 9.1% reported in women of similar age and lower iodine excretions of around 60 μg/L (23). The prevalence of hypothyroidism was also higher (7.1%) among women in the Wickham survey (30). Similarly, Hollowell et al. (31) reported a higher occurrence of hypothyroidism of 6% to 8% of the U.S. population of similar age to our population. These findings of a relatively low occurrence of hypothyroidism among Greenlandic Inuit even with high iodine intakes conform to our hypothesis of adaptation to a high-iodine diet. This hypothesis would be strengthened by an evaluation of the evolution over time of the iodine nutrition.
The Arctic environment causes cold exposure to the populations surveyed in Greenland. This may influence thyroid activity and the metabolism of T3, as activation of brown adipose tissue for heat production is dependent on T3, but not TSH levels (1,32,33). TG is a marker of thyroid activity and abnormalities (3,16,17), and the pattern of TG and fT3 in serum in Greenland Inuit is in keeping with the influence of cold on the thyroid (3). Levels of TG were higher among East than West Greenlanders conforming to the differences in lifestyle and were even higher among the more cold-exposed hunters and those living in settlements in East Greenland (3). TSH was unaltered. TSH plays an important role in NIS expression in the thyroid, but NIS expression was thus not influenced by cold via TSH in Inuit.
Limitations
First, our study population was limited to 50- to 69-year olds and therefore not representative of the entire Greenlandic population. Second, the number of participants was relatively low compared with other population studies. Still, we included 1% of the total population of Greenland. Third, the limited number of individuals with thyroid dysfunction prevents detailed analysis. Fourth, we did not include sonographic examinations of the thyroid, which could have been of interest. Finally, the occurrence of TPOAb is relevant to include in future studies of Inuit. Smoking was frequent in our population hampering comparisons with other studies. A strength of our study is that 95% of the 50- to 69-year olds attended the survey, resulting in a comprehensive representation of that age group. Another strength is that we collected both urine samples for iodine measurements and serum for thyroid functions tests, giving a credible description of the thyroid function in the Inuit population.
Conclusion
Our report is the first population-based study of thyroid function in Arctic people. The iodine-rich Arctic diet provided Inuit long-term adequate to more than adequate iodine intake, likely for centuries, which may have caused an adaptation to such high iodine intakes. This hypothesis is supported by our finding of a pattern of hyper- and hypothyroidism among iodine-replete Greenlandic Inuit comparable with those seen in populations with borderline iodine deficiency. The dietary transition with the traditional Arctic diet being replaced by a westernized diet is followed by a decreasing iodine intake. The lowering of the iodine intake in the Arctic populations to iodine-replete levels may have caused this pattern of thyroid diseases. Our findings are intriguing and fuel speculations on a genetic adaptation to iodine excess among Inuit with iodine abundancy for centuries.
Footnotes
Acknowledgments
We gratefully acknowledge the support by the nursing station staff in East Greenland and we appreciate the contribution to the study design and data collection by the late Professor Peter Laurberg.
Authors' Contributions
P.N.: Formal analysis, writing—original, draft, and visualization. K.F.R.: Data curation, and writing—review and editing. I.B.P.: Formal analysis, and writing—review and editing. G.M.: Resources and investigation. H.C.F.-S.: Resources and investigation. M.L.P.: Resources, investigation, and writing—review and editing. S.A.: Conceptualization, methodology, formal analysis, investigation, resources, data curation, supervision, project administration, funding acquisition, and writing—review and editing.
Data Availability
Restrictions apply to the availability of data to preserve patient confidentiality. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
The study was supported by grants from the Greenland Government and Karen Elise Jensen Fond (Grant No. 80.21).
