The Impact of Hypothyroidism on Satisfaction with Care and Treatment and Everyday Living: Results from E-Mode Patient Self-Assessment of Thyroid Therapy,a Cross-Sectional,International Online Patient Survey

Abstract

Background:

Hypothyroid patients often report dissatisfaction and poor quality of life. This survey explored the impact of hypothyroidism on patient satisfaction, everyday living, experiences with health care professionals, and influence of demographic and socioeconomic factors.

Methods:

Cross-sectional questionnaire survey targeting an international population of hypothyroid patients. Multilevel regression modeling was used for analyses.

Results:

The total number of responses was 3915 from 68 countries. Satisfaction with care and treatment was not associated with type of treatment for hypothyroidism. Having no confidence and trust in health care professionals was strongly associated with dissatisfaction (p < 0.001). Controlling for all other variables, significant differences were found among satisfaction rates between countries. A weak inverse relationship was found between satisfaction with care and treatment and impact on everyday living (p < 0.001). Respondents taking levothyroxine (LT4) alone were more likely to report a positive impact on everyday living (pooled odds ratio 2.376 [confidence interval: 0.941–5.997]) than respondents taking liothyronine-containing treatments.

Conclusions:

Low levels of satisfaction with care and treatment for hypothyroidism were strongly associated with lack of confidence and trust and negative experiences with health care professionals. Differences in responses between countries were noted, implying the potential influence of national health care systems, socioeconomic and cultural factors. Contrary to widespread anecdotes in social media, this large-scale survey shows no association between type of treatment for hypothyroidism and patient satisfaction, as well as better outcomes on everyday living associated with LT4, compared with liothyronine-containing treatments.

Introduction

Hypothyroidism is common with a prevalence of 1–7%.^1,2 It is 10 times more frequent in women than in men and the prevalence increases with advancing age.³ Most symptoms are nonspecific and the diagnosis is based on clinical evaluation and biochemical tests.^4,5 The standard treatment for hypothyroidism is daily administration of levothyroxine (LT4) tablets, which is simple, effective, and safe.⁶ Although patients report improved well-being on initiation of treatment, 5–35% suffer persistent symptoms^7

–10 even when achieving normal serum thyrotropin (TSH).^8,9,11 However, these findings have not been confirmed by other studies.^2,12
–14

Patient surveys have identified concerns about poor experience with health professionals, delays in diagnosis, persistent psychological and somatic complaints, dissatisfaction with LT4 formulations, and preference for treatment with l-triiodothyronine (LT3)-containing preparations over LT4.^15
–17 Persistent symptoms in patients on LT4 treatment result in multiple medical consultations, overinvestigation,³ and alternative treatments. The socioeconomic burden associated with this phenomenon is considerable.¹⁸ Understanding the etiology of persistent symptoms remains poor, although attention has centered around the hypothesis that in some patients LT4 treatment may be unable to restore normal hormone supply to all organs.¹⁹ However, several other unrelated factors may also contribute.^20,21 In particular, cultural influences on patient perceptions have never been studied. The topic of patient satisfaction and quality of life (QoL) for people being treated for hypothyroidism is consequently of considerable interest.²²

Research Questions

Primary research questions are as follows:

Which factors are associated with patient satisfaction with care and treatment?

Which factors are associated with the impact of hypothyroidism on everyday living?

Secondary research question is as follows:

What is the relationship between satisfaction with care and treatment and impact on everyday living?

Methods

Institutional Review Board waiver statement

The study was exempt from Institutional Board approval given the anonymous and noninterventional nature of the survey. The Danish National Committee on Health Research Ethics was approached with regard to waiver. The authors were informed that according to Danish law surveys of this nature do not require and thus cannot obtain approval by ethics committees. The research was completed in accordance with the Declaration of Helsinki as revised in 2013. Informed consent was submitted by respondents at the beginning of the survey.

Details about the construction of the survey instrument are given in Supplementary Data.

The survey was available in English, French, German, Italian, and Spanish. Dual translation was used in which two native, certified language translators each reviewed the text and replaced idioms with the closest equivalent. These translations were entered into the online survey platform Qualtrics to match the formatting of the English version.

Advertisements/information sheets to explain the purpose of the survey were prepared in the above five languages and promoted through Thyroid Federation International (TFI) affiliates and partners, TFI social media, and web pages. Participants were informed that the study was sponsored by a pharmaceutical company (IBSA) and were not reimbursed for participation.

Patients were eligible to take part in the survey if they were ≥18 years and currently taking medication for hypothyroidism. For the statistical model, cases were included if there were >10 responses from a single country, and responses were provided for country of residence, treatment for hypothyroidism, and the relevant dependent variable.

Statistical approach

Sample size estimation

For bivariate analysis, 1000 complete cases were deemed sufficient for subgroup analysis, with Gpower3.1.9 indicating a power to detect a delta 0.1 in proportions for z-tests. It was estimated that a sample size of ∼2500 complete cases (for the variables under consideration) would be required to detect small effects (odds ratio [OR] of 1.18 and Pr(y = 1 |x = 1 H0 = 02), and 1000 to detect medium effects (OR, 1.3) for a simple logistic regression model, using Gpower3.1.9. However, we expected country to be fitted as a cluster variable (to account for between-country differences) so simulations using MLwiN were conducted for multilevel modeling using standard assumptions, which indicated similar figures. As some analyses (not in this study) were to be conducted only with people currently taking LT4, expected to be ∼80% of respondents, and we anticipated missing data, we aimed for >3125 responses to detect small effects.

Modeling specification

For details on model specification please see Supplementary Data.

Dependent variables

Two survey items were converted to binary dependent variables. This was achieved by creating a variable coded as having a positive outcome as “1,” and neutral and negative outcomes as “0.” These variables were selected by the authors as having face validity and were confirmed as well understood by respondents during cognitive testing. Kendall's tau correlation coefficient was calculated between dependent variables before the binary conversion.

For item “How satisfied are you with the overall care and treatment you have received for your hypothyroidism?” positive outcomes coded as 1 were “Very Satisfied” and “Satisfied,” all others (“unsatisfied,” “very unsatisfied,” “neither satisfied nor unsatisfied,” “uncertain”) coded as 0 and the derived dependent variable is termed “Satisfaction.” Similarly, for item “My hypothyroidism has affected everyday activities that people my age usually do (e.g., exercise, household chores, etc.)” positive outcomes coded as 1 were “Tend to disagree” and “Strongly disagree,” all others (“tend to agree,” “strongly agree,” “neither agree nor disagree,” “uncertain”) coded as 0 and the derived dependent variable is termed “everyday living.”

Independent variables

The authors identified a priori 143 items as potential independent variables for the dependent variables. A reduced set of included independent variables for each dependent variable were distinguished from the potential independent variables, using a threshold of an absolute value of 0.3 for the nonparametric correlations on the “pooled estimate” from the imputed data set. No demographic variables met the inclusion criteria for either model. A variable for treatment combination was included for statistical elimination of effect (see Supplementary Data, under Modeling specifications).^{23

–30}

Results

Respondent demographic characteristics

A total of 3915 people from 68 countries responded (3420 complete and 495 partial responses) (Table 1). Women comprised 93.8% (3668/3910) of respondents, 74.8% (2568/3431) were older than 41 years and responses from the United Kingdom dominated (36.0%, 1332/3702). The majority (92.0%, 3152/3425) were white, employed (58.0%, 1985/3425), and had received >12 years of education (77.1%, 2640/3426). Most respondents (81.4%, 2733/3357) had comorbidities.

Table 1.

Respondent Characteristics

	Full data set (N = 3915)		In Satisfaction model (N = 2751)		In Impact on day living model (N = 2604)
	n	%	n	%	n	%
Gender	3910		2750		2603
Man	198	5.1	136	4.9	126	4.8
Woman	3668	93.8	2599	94.5	2462	94.6
Prefer to self-identify	18	0.5	8	0.3	8	0.3
Prefer not to say	26	0.7	7	0.3	7	0.3
Age, years	3431		2638		2516
18–40	863	25.2	673	25.5	650	25.8
41–60	1858	54.2	1436	54.4	1370	54.5
Over 60	710	20.7	529	20.1	496	19.7
Top 10 countries by respondent number (from main data)	3702		2751		2604
United Kingdom	1332	36.0	1064	38.7	1031	39.6
France	663	17.9	460	16.7	431	16.6
Sweden	210	5.7	160	5.8	151	5.8
Finland	159	4.3	126	4.6	117	4.5
Australia	148	4.0	119	4.3	114	4.4
Italy	139	3.8	93	3.4	87	3.3
Germany	121	3.3	89	3.2	83	3.2
Norway	113	3.1	80	2.9	76	2.9
United States	112	3.0	88	3.2	80	3.1
Canada	111	3.0	89	3.2	86	3.3
Employment status	3425		2635		2513
Working (full time, part time)	1985	58.0	1562	59.3	1493	59.4
Not working	1127	32.9	842	32.0	797	31.7
Full-time carer	49	1.4	37	1.4	37	1.5
Student	68	2.0	58	2.2	57	2.3
Prefer not to say	60	1.8	43	1.6	43	1.7
Other	136	4.0	93	3.5	86	3.4
Ethnic background	3425		2636		2514
White	3152	92.0	2453	93.1	2335	92.9
Mixed/multiple ethnic groups	45	1.3	33	1.3	32	1.3
Asian	60	1.8	39	1.5	40	1.6
Black/African/Afro-Caribbean	24	0.7	15	0.6	15	0.6
Middle Eastern/Arab	20	0.6	11	0.4	11	0.4
Latino (descended from Latin America)	48	1.4	28	1.1	26	1.0
Other (please specify)	21	0.6	13	0.5	13	0.5
Prefer not to say	55	1.6	44	1.7	42	1.7
Years of education	3426		2635		2513
<8 years	273	8.0	202	7.7	190	7.6
9–16 years	1456	42.5	1160	44.0	1106	44.0
>16 years	1617	47.2	1216	46.1	1169	46.5
Prefer not to say	80	2.3	57	2.2	48	1.9
Household economic status	3385		2606		2486
Above average	1085	32.1	827	31.7	795	32.0
Average	1536	45.4	1204	46.1	1140	45.9
Below average	635	18.8	495	18.4	463	18.6
Prefer not to say	129	3.8	131	3.8	88	3.5
10 most common comorbidities (ordered from main data set)	3357		2467		2340
Mental health condition (e.g., depression, anxiety)	912	27.2	680	27.6	648	27.7
Gastrointestinal disease (e.g., irritable bowel syndrome, celiac disease)	762	22.7	542	22.0	527	22.5
Joint problem (e.g., arthritis or other rheumatic disease)	723	21.5	530	21.5	508	21.7
Chronic pain (e.g., back pain)	721	21.5	524	21.2	503	21.5
No long-term condition	623	18.6	476	19.3	446	19.1
Food allergy (e.g., gluten intolerance)	573	17.1	382	15.5	363	15.5
Autoimmune disease (other than thyroid)	564	16.8	409	16.6	383	16.4
Fatigue syndrome (e.g., chronic fatigue, myalgic encephalomyelitis)	551	16.4	363	14.7	347	14.8
Other long-term condition	545	16.2	413	16.7	400	17.1
Lung disease (e.g., asthma, chronic obstructive pulmonary disease)	350	10.4	264	10.7	254	10.9
Prescribed medications for any condition other than hypothyroidism	3127		2271		2154
Yes	1842	58.9	1392	61.3	1320	61.3
No	1285	41.1	879	38.7	834	38.7

Respondent hypothyroidism characteristics

Information about hypothyroidism is summarized in Table 2: 51.6% (1961/3802) had received a diagnosis of hypothyroidism >10 years earlier and 84.5% (2720/3218) were being treated with LT4. The highest serum TSH ever recorded was <4 mU/L in 15.7% (410/2617), 4–10 mU/L in 36.0% (941/2617), and >10 mU/L in 48.4% (1266/2617). LT4, LT3, and LT4+LT3 were available as treatments for hypothyroidism in all countries included in the model (Supplementary Table S1). Almost half of the respondents (48.0%, 1735/3615) expressed dissatisfaction with care and treatment in relation to their diagnosis of hypothyroidism, and the majority (69.4%, 2469/3558) stated that hypothyroidism had negatively affected their everyday living.

Table 2.

Respondent Hypothyroidism Characteristics

	Full data set		In Satisfaction model		In Impact on day living model
	n	%	n	%	n	%
Time since diagnosis of hypothyroidism	3802		2703		2560
<2 years	406	10.7	264	9.8	257	10.0
2–10 years	1435	37.7	1041	38.5	990	38.7
>10 years	1961	51.6	1398	51.7	1313	51.3
Current treatment for hypothyroidism	3218		2751		2604
LT4	2720	84.5	2307	83.9	2177	83.6
LT3	60	1.9	54	2.0	52	2.0
DTE	150	4.7	136	4.9	128	4.9
LT4+LT3	288	8.9	254	9.2	247	9.5
Cause of hypothyroidism	3025		2109		1998
Hashimoto/autoimmune disease	1394	46.1	961	45.6	917	45.9
Treatment for Graves' disease or hyperthyroidism	320	10.6	233	11.0	220	11.0
Treatment for thyroid cancer	520	17.2	375	17.8	360	18.0
Treatment for benign goiter	197	6.5	136	6.4	129	6.5
Pregnancy related	149	4.9	111	5.3	102	5.1
Other	445	14.7	293	13.9	270	13.5
Time since most recent TSH blood test	3866		2730		2583
Within the last 2 months	1760	45.5	1205	44.1	1139	44.1
Between 2 and 6 months	1083	28.0	772	28.3	744	28.8
Between 6 and 12 months	619	16.0	464	17.0	437	16.9
More than 12 months	404	10.5	289	10.6	263	10.2
Value of most recently measured TSH (mU/L)	2997		2050		1954
Under 0.1	547	18.3	354	17.3	339	17.3
Between 0.1 and 0.4	631	21.1	411	20.0	398	20.4
Between 0.41 and 4.0	1345	44.9	970	47.3	915	46.8
Between 4.1 and 10	324	10.8	220	10.7	216	11.1
More than 10	150	5.0	95	4.6	86	4.4
Highest ever recorded TSH level (mU/L)	2617		1792		1707
<4.0	410	15.7	279	15.6	265	15.5
Between 4.0 and 10	941	36.0	630	35.2	597	35.0
>10	1266	48.4	883	49.3	845	49.5

DTE, desiccated thyroid extract; LT3, L-triiodothyronine; LT4, levothyroxine; TSH, thyrotropin.

Modeling results

Satisfaction with care and treatment

There were 2751 eligible cases of which 36.7% (1010/2751) had a positive outcome (i.e., were satisfied with care and treatment). All imputation regressions were significant overall, with a pooled correct classification of 81.0% (i.e., the model correctly predicted the outcome for four-fifths of the cases). A design effect of >2 indicates the need to account for the clustering of responses. In this case the calculated design effect was 22.4. However, the pooled p-value for the random intercept for that cluster variable was 0.052, demonstrating no overall significance for the cluster variable.

Cases from France, Greece, and the Philippines had intercepts with significant ORs (worse Satisfaction for respondents from France, whereas it was better for Greece and the Philippines than all other countries; Table 3).

Table 3.

Pooled Estimates for the Random Intercepts in the Multiply Imputed Multilevel Logistic Regression Model for Satisfaction (Binary Satisfaction with Care and Treatment), to Three Decimal Places

Country	Standard error	Estimated coefficient	Confidence interval of estimate	Median p-value	Exponentiated coefficient (odds ratio)	Confidence interval of odds ratio
Argentina	0.640	0.230	[−1.024 to 1.484]	0.580	1.259	[0.359 to 4.412]
Australia	0.504	−0.254	[−1.242 to 0.734]	0.318	0.776	[0.289 to 2.084]
Belgium	0.602	−0.410	[−1.589 to 0.770]	0.294	0.664	[0.204 to 2.159]
Canada	0.522	−0.095	[−1.119 to 0.929]	0.748	0.909	[0.327 to 2.531]
Croatia	0.600	−0.469	[−1.645 to 0.707]	0.203	0.626	[0.193 to 2.028]
Denmark	0.644	0.463	[−0.8 to 1.725]	0.237	1.588	[0.450 to 5.610]
Finland	0.507	−0.296	[−1.289 to 0.697]	0.227	0.744	[0.275 to 2.008]
France	0.432	−0.949	[−1.796 to 0.103]	0.000	0.387	[0.166 to 0.902]
Germany	0.525	0.002	[−1.026 to 1.031]	0.937	1.002	[0.358 to 2.803]
Greece	0.704	1.085	[−0.296 to 2.466]	0.006	2.959	[0.744 to 11.77]
Ireland	0.695	0.118	[−1.245 to 1.48]	0.818	1.125	[0.288 to 4.395]
Italy	0.524	0.071	[−0.956 to 1.098]	0.814	1.074	[0.384 to 2.998]
Kenya	0.697	0.152	[−1.213 to 1.517]	0.749	1.164	[0.297 to 4.560]
Mexico	0.645	−0.092	[−1.357 to 1.172]	0.805	0.912	[0.258 to 3.228]
The Netherlands	0.595	−0.366	[−1.531 to 0.800]	0.292	0.694	[0.216 to 2.226]
Norway	0.535	0.195	[−0.853 to 1.243]	0.495	1.215	[0.426 to 3.465]
Philippines	0.642	0.994	[−0.265 to 2.253]	0.017	2.703	[0.767 to 9.520]
Spain	0.538	−0.217	[−1.272 to 0.838]	0.411	0.805	[0.280 to 2.313]
Sweden	0.505	−0.249	[−1.238 to 0.740]	0.326	0.780	[0.290 to 2.096]
Switzerland	0.564	0.319	[−0.786 to 1.424]	0.309	1.376	[0.456 to 4.152]
United Kingdom	0.418	0.005	[−0.814 to 0.824]	0.902	1.005	[0.443 to 2.279]
United States	0.526	−0.238	[−1.268 to 0.793]	0.402	0.789	[0.281 to 2.211]

The reference group (LT4 treatment) was more likely to have a good outcome for satisfaction (pooled OR, 10.647; confidence interval [CI: 4.474–25.336]) than other treatment groups (across all variables in the model). However, when taking each variable in turn while holding all others constant, there was no overall significant effect for treatment type on satisfaction with care and treatment (pooled p-value = 0.351).

Poor satisfaction with care and treatment of hypothyroidism correlated with: (Table 4):

Table 4.

Fixed Effects Table, Odds Ratios and Confidence Interval for Odds Ratio Exponentiated from Coefficient Estimates for Satisfaction

Question	Response	Median p-value	Exponentiated coefficient (odds ratio)	95% confidence interval of odds ratio
Intercept		0	10.647	4.474–25.336
What are you currently taking to treat your hypothyroidism?
	LT4+LT3	0.596	0.895	0.381–2.101
	Desiccated thyroid extract (DTE) alone	0.217	0.711	0.259–1.953
	LT3 alone	0.352	0.674	0.194–2.347
	LT4 alone
Do you have confidence and trust in the health care staff treating your hypothyroidism?
	No	0	0.195	0.075–0.505
	Yes, sometimes	0.002	0.633	0.296–1.355
	Yes, always
Do the health care staff that you see for your hypothyroidism know enough about the condition?
	No	0	0.41	0.162–1.038
	Yes, to some extent	0.007	0.691	0.333–1.435
	Yes, definitely
Do you have enough time to talk and interact with health care staff about your hypothyroidism?
	No	0	0.54	0.23–1.266
	Yes, to some extent	0.117	0.796	0.369–1.718
	Yes, definitely
Are you involved enough in decisions about your condition and treatment?
	I do not want or need to be	0.206	0.582	0.155–2.182
	No, but I would like this	0	0.314	0.142–0.694
	Yes, to some extent	0	0.579	0.285–1.178
	Yes, definitely
Do health care staff talk to you about your care and treatment in a way that you can understand?
	No, but I would like this	0.001	0.5	0.200–1.247
	Yes, to some extent	0	0.599	0.293–1.224
	Yes, definitely
Still thinking about taking your hypothyroidism medication in the past 12 months, how burdensome (if at all) have any of the following been?—Making sure that I am getting blood tests done to make sure I am taking the right dose
	Extremely burdensome	0	0.301	0.123–0.735
	Moderately burdensome	0	0.437	0.199–0.957
	Slightly burdensome	0.153	0.839	0.42–1.674
	Not burdensome at all
Have you been given enough information about when and how to take your hypothyroidism medication?
	I do not want or need to be	0.004	0.535	0.213–1.344
	No, but I would like this	0	0.29	0.127–0.664
	Yes, to some extent	0.058	0.772	0.373–1.6
	Yes, definitely

respondents having no confidence and trust in health care staff (OR, 0.195 [CI: 0.075–0.505], p < 0.001)

respondent perception that health care staff had insufficient knowledge about hypothyroidism (OR, 0.410 [CI: 0.162–1.038], p < 0.001)

respondents not given enough time to talk and interact with health care staff (OR, 0.540 [CI: 0.230–1.266], p < 0.001)

respondents not involved in decisions about their condition and treatment (OR, 0.314 [CI: 0.142–0.694], p < 0.001)

respondents feeling that health care staff did not talk to them in an understandable way (OR, 0.500 [CI: 0.200–0.247], p < 0.001)

respondents feeling that having thyroid blood tests was extremely burdensome (OR, 0.301 [CI: 0.123–0.753], p < 0.001)

respondents feeling that they had not received enough information about the hypothyroidism medication (OR, 0.290 [CI: 0.127–0.664], p < 0.001)

Satisfaction with care and treatment was unrelated to several other variables (Supplementary Table S1).

Impact on everyday living

There were 2604 eligible responses of which 18.0% (469/2604) had a positive outcome (i.e., hypothyroidism did not negatively affect everyday living). The pooled correct classification of the models was 84.6%. The cluster variable was determined as necessary by the design effect (21.1), and the pooled p-value for the random intercept was 0.032. Cases from France, the Philippines, and Switzerland had intercepts with significant ORs (worse “Impact on everyday living” for respondents from the Philippines, better for France and Switzerland, than other countries; Table 5). There was an overall significant effect for treatment type (pooled p-value = 0.002), with most treatment types other than LT4 alone estimated as more likely to have a poorer impact on everyday living (Table 6) (LT4+LT3 vs. LT4: OR, 0.455 [CI: 0.175–1.181], p = 0.001; DTE vs. LT4: OR, 0.646 [CI: 0.233–1.796]), p > 0.05; LT3 vs. LT4: OR, 0.435 [CI: 0.112–1.696], p > 0.05).

Table 5.

Table of Pooled Estimates for the Random Intercepts in the Multiply Imputed Multilevel Logistic Regression Model for Impact on Everyday Living, to Three Decimal Places

Country	Standard error	Estimated coefficient	95% confidence interval of estimate	Median p-value	Exponentiated coefficient (odds ratio)	95% confidence interval of odds ratio
Argentina	0.675	−0.037	[−1.359 to 1.285]	0.947	0.964	[0.257 to 3.614]
Australia	0.541	−0.160	[−1.219 to 0.9]	0.576	0.852	[0.295 to 2.459]
Belgium	0.639	0.121	[−1.131 to 1.373]	0.769	1.129	[0.323 to 3.947]
Canada	0.551	0.091	[−0.99 to 1.172]	0.775	1.095	[0.372 to 3.228]
Croatia	0.687	−0.650	[−1.996 to 0.697]	0.171	0.522	[0.136 to 2.007]
Denmark	0.655	0.263	[−1.02 to 1.546]	0.543	1.301	[0.36 to 4.693]
Finland	0.536	0.327	[−0.724 to 1.378]	0.260	1.387	[0.485 to 3.969]
France	0.459	0.419	[−0.481 to 1.319]	0.045	1.521	[0.618 to 3.739]
Germany	0.535	0.460	[−0.588 to 1.508]	0.108	1.584	[0.555 to 4.519]
Greece	0.665	0.093	[−1.21 to 1.396]	0.833	1.097	[0.298 to 4.038]
Ireland	0.731	−0.187	[−1.62 to 1.246]	0.726	0.829	[0.198 to 3.475]
Italy	0.570	−0.844	[−1.961 to 0.273]	0.010	0.430	[0.141 to 1.313]
Kenya	0.768	0.194	[−1.311 to 1.699]	0.742	1.214	[0.269 to 5.467]
Mexico	0.696	−0.125	[−1.489 to 1.239]	0.779	0.883	[0.226 to 3.453]
The Netherlands	0.673	−0.331	[−1.65 to 0.988]	0.466	0.718	[0.192 to 2.687]
Norway	0.597	−0.392	[−1.563 to 0.779]	0.278	0.676	[0.21 to 2.178]
Philippines	0.699	−0.997	[−2.366 to 0.373]	0.041	0.369	[0.094 to 1.451]
Spain	0.586	−0.017	[−1.167 to 1.132]	0.956	0.983	[0.311 to 3.103]
Sweden	0.530	−0.002	[−1.04 to 1.036]	0.991	0.998	[0.353 to 2.818]
Switzerland	0.558	1.571	[0.476 to 2.665]	0.000	4.811	[1.61 to 14.371]
United Kingdom	0.438	−0.106	[−0.964 to 0.752]	0.585	0.900	[0.381 to 2.121]
United States	0.558	0.309	[−1.359 to 1.285]	0.317	1.362	[0.257 to 3.614]

Table 6.

Fixed Effects Table, Odds Ratios and Confidence Interval for Odds Ratio Exponentiated from Coefficient Estimates for Impact on Everyday Living

Question	Response	Median p-value	Exponentiated coefficient (odds ratio)	95% confidence interval of odds ratio
Intercept		0	2.376	[0.941–5.997]
What are you currently taking to treat your hypothyroidism?
	LT4+LT3	0.001	0.455	[0.175–1.181]
	DTE alone	0.108	0.646	[0.233–1.796]
	LT3 alone	0.084	0.435	[0.112–1.696]
	LT4 alone
During the past four weeks, how much have you been bothered by any of the following problems?—feeling tired or having low energy
	Bothered a lot	0	0.141	[0.058–0.34]
	Bothered a little	0	0.369	[0.162–0.839]
	Not bothered at all/not applicable
During the past four weeks, how much have you been bothered by any of the following problems?—muscle weakness/cramps/aches
	Bothered a lot	0	0.307	[0.129–0.735]
	Bothered a little	0	0.551	[0.271–1.118]
	Not bothered at all/not applicable
During the past four weeks, how much have you been bothered by any of the following problems?—difficulty concentrating
	Bothered a lot	0.021	0.591	[0.237–1.477]
	Bothered a little	0	0.579	[0.276–1.214]
	Not bothered at all/not applicable
During the past four weeks, how much have you been bothered by any of the following problems?—slow speech, movements, or thoughts
	Bothered a lot	0	0.32	[0.106–0.962]
	Bothered a little	0.009	0.667	[0.309–1.439]
	Not bothered at all/not applicable

A negative impact of hypothyroidism on everyday living correlated with:

feeling tired or having low energy in the last 4 weeks (“bothered a little,” OR, 0.369 [CI: 0.162–0.839], p < 0.001; “bothered a lot,” OR: 0.141 [CI: 0.058–0.340], p < 0.001);

experiencing muscle weakness/cramps/aches in the last 4 weeks (“bothered a little,” OR, 0.551 [CI: 0.271–1.118], p < 0.001; “bothered a lot,” OR, 0.307 [CI: 0.129–0.735], p < 0.001);

experiencing difficulty concentrating in the last 4 weeks (“bothered a little,” OR, 0.579 [CI: 0.276–1.214], p < 0.001; “bothered a lot,” OR, 0.591 [CI: 0.237–1.477], p = 0.021);

experiencing slow speech, movements, or thoughts in the last 4 weeks (“bothered a little,” OR 0.667 [CI: 0.309–1.439], p = 0.009; “bothered a lot,” OR 0.320 [CI: 0.106–0.962], p < 0.001).

The group of people taking LT4 alone and having the best case for all candidate variables was more likely to have a positive impact on everyday living (pooled OR, 2.376 [CI: 0.941–5.997]) than all other groups.

Relationship between satisfaction with care and treatment and impact on everyday living

A weak inverse relationship was found between satisfaction with care and treatment and impact on everyday living (Kendall's tau, −0.279 [p < 0.001]).

Discussion

Unlike other hypothyroid patient surveys, E-Mode Patient self-Assessment of THYroid therapy (E-MPATHY) reached out to the global hypothyroid community, utilized professional expertise in survey design, methodology and statistical handling, and patient involvement. The demographic characteristics of respondents match those reported in epidemiological studies^3,31

–34 as do the range of causes of hypothyroidism.^3,35 The E-MPATHY cohort reported lower levels of use of LT4+LT3 and DTE than other surveys,^16,17 which is closer to those in the general hypothyroid population.^15,36 There is a tendency for patients who have poor health-related experiences to be overrepresented in such surveys, although the number of responses received and the multilevel regression modeling used reduces the random errors; however, the systematic error (bias) owing to overrepresentation cannot be discounted.^16,17,37

It is notable that 15.7% of responders reported that the highest ever recorded serum TSH value was <4.0 mU/L. In addition, 36.0% treated with thyroid hormones had a pretreatment serum TSH between 4.0 and 10 mU/L (subclinical hypothyroidism). These findings are consistent with studies that had access to laboratory results.^38,39 The fact that 51.9% of responders had a recent serum TSH outside the reference range, is in keeping with other studies,^5,40,41 and highlights that many patients are exposed to increased risks of morbidity and mortality associated with poor biochemical control.^42,43

The finding that satisfaction with care and treatment was independent of type of treatment for hypothyroidism, contrasts with those of a large U.S.-based patient survey,¹⁶ but is in agreement with a U.K. study.¹⁷ A likely explanation is that E-MPATHY and the U.K. study¹⁷ included parameters that related to the medical consultation as covariates. E-MPATHY has highlighted that having no confidence and trust in health care professionals correlated negatively with satisfaction with care and treatment of hypothyroidism. Although causality cannot be inferred, it is plausible that the medical consultation occupies a critical role in determining patient outcomes.

E-MPATHY found significant differences in satisfaction rates between countries, being highest among respondents from Greece and the Philippines and lowest from Northern Europe, which is consistent with reports from physician surveys,^{14,44

–58} the potential influence of national health care systems, socioeconomic and cultural factors.⁵⁹

Treatment with LT4 was associated with a better impact of hypothyroidism on everyday living than LT4+LT3 or DTE, which contrasts with a U.S. study.¹⁶ This difference may be related to varying cultural backgrounds of respondents, as well as inclusion of different covariates in the multivariate analyses. As expected, an inverse relationship was found between satisfaction with care and treatment and the impact of hypothyroidism on everyday living, but this was weak. This is not surprising as satisfaction with care and treatment is only one of the several parameters that may impact on everyday living, an extreme example being patients with terminal diseases where their satisfaction with palliative care may be high, but the impact of the underlying disease devastating.⁶⁰

In the past two decades attention has focused on treatment of hypothyroidism with LT4+LT3 or DTE, and continues to interest investigators.⁶¹ Evidence from randomized controlled trials suggests lack of superiority of such treatments over LT4, although most were underpowered.²² E-MPATHY highlights the potential role of the medical consultation and cultural influences that bear on patient perceptions of treatment efficacy and therefore satisfaction with care and treatment and resulting impact on everyday living. E-MPATHY suggests that improving aspects of the medical consultation and use of nonpharmacological interventions^62
–64 may be important strategies in addressing persistent symptoms.

Limitations of the study included the following: self-reported responses that could not be validated independently; overrepresentation of some countries; recruitment through social media; heterogeneous sample; cognitive testing having been conducted only in English; and the percentage of dissatisfied respondents with care and treatment was greater among the eligible cases for modeling (63.3%) than those in the entire sample (48.0%). In addition, the impact on everyday living was not assessed through a validated QoL instrument and the study did not include data on satisfaction with care and treatment or impact on everyday living before switching from LT4 to other treatments. To mitigate against these shortcomings, cognitive testing of the questionnaire with a sample of patients, followed by a pilot was used to maximize consistency of responses. Although a single question was used as a proxy for QoL, good face validity and response was demonstrated in pilot work; the analyses were conducted using a robust modeling approach; the global sample enabled inclusion of responders from a wide range of cultural backgrounds; the participation of a patient representative in the research team ensured inclusion of the patient perspective and that the survey was lay-person friendly.

Conclusions

E-MPATHY has shown that low levels of satisfaction with care and treatment for hypothyroidism were strongly associated with lack of confidence and trust and negative experiences with health care professionals. Treatment with LT4 was associated with a lower impact on everyday living compared with LT3-containing treatments. Differences in respondent satisfaction with care and treatment and impact on everyday living between countries were noted, implying cultural influences. Contrary to widespread anecdotes in social media, this large-scale survey shows no association between type of treatment for hypothyroidism and patient satisfaction, as well as better outcomes on everyday living associated with LT4, compared with LT3-containing treatments.

Footnotes

Authors' Contributions

P.P.: Conceptualization (lead); methodology (equal), supervision (equal), writing—review and editing (lead). L.H.: Conceptualization (equal); funding acquisition (lead), methodology (equal), writing—review and editing (equal). E.V.N: Conceptualization (equal), methodology (equal), writing—review and editing (equal). E.P.: Conceptualization (equal), methodology (equal), writing—review and editing (equal). H.A.H.: Data curation (equal), investigation (equal); methodology (equal), project administration (lead), supervision (equal), writing—review and editing (equal). J.A.-M.: Data curation (equal); formal analysis (equal), software (equal), writing—review and editing (equal), project administration (equal). A.J.T.: Investigation (lead), methodology (lead), project administration (equal), supervision (lead), writing—review and editing (equal). M.B.: Investigation (equal), methodology (equal), project administration (equal), supervision (equal), writing—review and editing (equal). P.L.: Resources (lead), methodology (equal), writing—review and editing (equal), Investigation (equal). A.J.P.: Methodology—statistical modeling (lead), data curation (lead), software (lead), writing—review and editing (equal); formal analysis (lead), writing—original draft (lead), writing—review and editing (equal).

Acknowledgments

The authors thank Steven Sizmur for his help with the statistical analyses and the patient organizations and their members for disseminating the survey and for responding to the questionnaire.

Author Disclosure Statement

P.P. reports honoraria from IBSA Institut Biochimique SA. L.H. reports honoraria from IBSA Institut Biochimique SA. E.V.N. reports honoraria from IBSA Institut Biochimique SA. E.P. reports honoraria from IBSA Institut Biochimique SA. The other authors report no competing financial interests.

Funding Information

This study was funded by IBSA Institut Biochimique SA, who had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.

Supplementary Material

Supplementary Data

Supplementary Table S1

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