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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 21  |  Issue : 4  |  Page : 403-409  

Obstructive sleep apnea in hypothyroidism


1 Department of Medicine, K.G.M.U, Lucknow, Uttar Pradesh, India
2 Department of Cardiology, K.G.M.U, Lucknow, Uttar Pradesh, India
3 Department of Respiratory Medicine, K.G.M.U, Lucknow, Uttar Pradesh, India

Date of Submission29-Jun-2021
Date of Decision07-Sep-2021
Date of Acceptance20-Dec-2021
Date of Web Publication16-Nov-2022

Correspondence Address:
Shyam Chand Chaudhary
Department of Medicine, K.G.M.U, Lucknow - 226 016, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aam.aam_134_21

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   Abstract 


Introduction: Obstructive sleep apnea (OSA) and hypothyroidism are closely linked as hypothyroidism has been shown to lead to the development of OSA through multiple mechanisms. With the changing lifestyle patterns worldwide and increased prevalence of obesity, the burden of OSA has substantially increased. The association of OSA with hypothyroidism is essential to establish. If identified early, treatment of OSA and associated hypothyroidism can be done timely to minimize the potential harmful complications of OSA on all aspects of the patient's health. Aims: This study was done to find out the prevalence of OSA in hypothyroidism patients. Setting and Designs: It was a cross-sectional study, done over a period of 1 year in a tertiary care hospital. Materials and Methods: A total of 100 hypothyroidism patients were enrolled after taking written consent. All patients were subjected to STOP-Bang questionnaire and patient falling in intermediate-high risk (score3-8), were taken for overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Statistical Analysis Used: The Statistical Package for the Social Sciences version 21.0 statistical analysis software. Results: Out of 100 patients, who underwent polysomnography, 74 (74%) cases had OSA (AHI ≥5). Out of total 74 OSA cases, 29 (39.2%) cases had mild OSA (AHI 5–14), 15 (20.3%) cases had moderate OSA (AHI 15–30), and 30 (40.5%) cases had severe OSA. The age of the study population ranged between 24 and 78 years and the mean age was 58.28 ± 11.22 years. The mean age of the patients in the OSA group (59.27 ± 11.17 years) was higher than the non-OSA group (55.46 ± 11.09 years). Majority (64%) of our cases were male, and the proportion of males was found to be higher than females in both the groups (OSA/non-OSA). The body mass index (BMI) of the OSA group was found to be statistically higher as compared to that of the non-OSA group (P = 0.040). The BMI was found to be higher in severe OSA, but it was not statistically significant (P = 0.128). The mean value of FT4 was lower and thyroid-stimulating hormone (TSH) was higher in the OSA group as compared with the non-OSA group. However, no significant association was found between FT4 and TSH values in both the groups. Out of 100 cases, 41 patients were treatment naïve with mean TSH value of 13.1 ± 7 and 59 were on treatment with mean TSH of 8.3 ± 4. Treatment-naïve patients had a statistically higher number (85.3%) of OSA cases in comparison to patients on treatment (66.1) (P = 0.030). Conclusions: Prevalence of OSA is quite high in hypothyroidism. Patients with hypothyroidism should be screened for OSA for early diagnosis, especially in individuals with higher BMI. Treatment of hypothyroidism reduces the prevalence of OSA.

   Abstract in French 

Résumé
Introduction: L'apnée obstructive du sommeil (OSA) et l'hypothyroïdie sont étroitement liées car l'hypothyroïdie s'est avérée conduire au développement de l'AOS à travers de multiples mécanismes. Avec l'évolution des modèles de style de vie dans le monde et une prévalence accrue de l'obésité, le fardeau de l'AOS a considérablement augmenté. L'association de l'AOS avec l'hypothyroïdie est essentielle à établir. S'il est identifié tôt, le traitement de l'AOS et de l'hypothyroïdie associée peuvent être effectués en temps opportun pour minimiser les complications nocives potentielles de l'AOS sur tous les aspects de la santé du patient. Aims: Cette étude a été réalisée pour découvrir la prévalence de l'AOS chez les patients hypothyroïdiennes. Cadre et conception: C'était une étude transversale, réalisée sur une période de 1 an dans un hôpital de soins tertiaires. Matériaux et méthodes: Un total de 100 patients hypothyroïdiennes ont été inscrits après avoir pris consentement écrit. Tous les patients ont été soumis à un questionnaire d'arrêt de bang et à la chute des patients à risque élevé (score3-8), ont été pris pour la polysomnographie d'une nuit pour confirmer le diagnostic de l'AOS (AHI ≥5). Analyse statistique utilisée: Le logiciel Statistical Package for the Social Sciences Version 21.0 Analyse statistique. Résultats: Sur 100 patients, qui ont subi une polysomnographie, 74 (74%) cas avaient une OSA (AHI ≥5). Sur le total de 74 cas d'ASA, 29 (39,2%) avaient des cas légers de l'ASA (AHI 5–14), 15 (20,3%) avaient des cas d'ASA modérés (AHI 15-30), et 20 (40,5%) avaient une OSA sévère. L'âge de la population d'étude variait entre 24 et 78 ans et l'âge moyen était de 58,28 ± 11,22 ans. L'âge moyen des patients du groupe OSA (59,27 ± 11,17 ans) était plus élevé que le groupe non-OSA (55,46 ± 11,09 ans). La majorité (64%) de nos cas étaient des hommes, et la proportion d'hommes s'est révélée plus élevée que les femmes dans les deux groupes (OSA / non-OSA). L'indice de masse corporelle (IMC) du groupe OSA s'est avéré statistiquement plus élevé par rapport à celui du groupe non-OSA (P = 0,040). L'IMC s'est avéré être plus élevé dans l'OSA sévère, mais il n'était pas statistiquement significatif (p = 0,128). La valeur moyenne de FT4 était inférieure et l'hormone stimulante thyroïdienne (TSH) était plus élevée dans le groupe OSA par rapport au groupe non-OSA. Cependant, aucune association significative n'a été trouvée entre les valeurs FT4 et TSH dans les deux groupes. Sur 100 cas, 41 patients étaient naïfs de traitement avec une valeur TSH moyenne de 13,1 ± 7 et 59 étaient sous traitement avec une TSH moyenne de 8,3 ± 4. Les patients naïfs de traitement avaient un nombre statistiquement plus élevé (85,3%) des cas d'AOS par rapport à patients sous traitement (66,1) (p = 0,030). Conclusions: La prévalence de l'AOS est assez élevée en hypothyroïdie. Les patients atteints d'hypothyroïdie doivent être dépistés pour l'AOS pour un diagnostic précoce, en particulier chez les personnes atteintes d'IMC plus élevée. Le traitement de l'hypothyroïdie réduit la prévalence de l'AOS.

Mots-clés: Indice d'apnée - hypene, indice de masse corporelle, hypothyroïdie, apnée obstructive du sommeil, polysomnographie, ronflement, fatigue pendant la journée, apnée observée et hypertension, indice

Keywords: Apnea–Hypopnea Index, body mass index, hypothyroidism, obstructive sleep apnea, polysomnography, Snoring, Tiredness during daytime, Observed apnea, and high blood Pressure, Body mass index, Age, Neck circumference, and Gender questionnaire


How to cite this article:
Pancholi C, Chaudhary SC, Gupta KK, Sawlani KK, Verma SK, Singh A, Verma AK, Usman K, Atam V. Obstructive sleep apnea in hypothyroidism. Ann Afr Med 2022;21:403-9

How to cite this URL:
Pancholi C, Chaudhary SC, Gupta KK, Sawlani KK, Verma SK, Singh A, Verma AK, Usman K, Atam V. Obstructive sleep apnea in hypothyroidism. Ann Afr Med [serial online] 2022 [cited 2022 Nov 29];21:403-9. Available from: https://www.annalsafrmed.org/text.asp?2022/21/4/403/361253




   Introduction Top


Hypothyroidism and obstructive sleep apnea (OSA) are relatively common diseases worldwide. Hypothyroidism can involve multiple systems including respiratory system and cardiovascular system, resulting in increased risk of morbidities and mortalities.[1],[2] The respiratory symptoms of hypothyroidism can range from mild dyspnea to more severe respiratory failure, which can be fatal. Undergoing pathophysiologies are mucopolysaccharide accumulation in the dermis, hypopharynx, tongue, and other tissues; respiratory muscle weakness; and reduction in central respiratory drive. In addition, patients with hypothyroidism may be at greater risk for developing OSA due to multiple factors including obesity.[3],[4],[5],[6],[7]

OSA and hypothyroidism share similar symptoms including excessive daytime sleepiness, apathy and feeling lethargic, periorbital edema, pedal edema, decreased cognitive function, decreased libido, obesity, and depressed mood making these two disorders difficult to tease apart based on patient's history and physical examination.[8],[9],[10] Nevertheless, snoring which is a hallmark of OSA is also reported in hypothyroid cases.[9],[11] Our study was aimed to see the prevalence of OSA in hypothyroidism, so that OSA can be recognized early in hypothyroid patients and can be treated appropriately. It will also be helpful to prevent further complications due to OSA in hypothyroid patients.


   Materials and Methods Top


This cross-sectional study entitled to study the prevalence of OSA in hypothyroid patients was conducted in the Department of Medicine in collaboration with Respiratory Medicine, Physiology, and Department of Ear, Nose, and Throat at a tertiary care hospital in northern India over a period of 1 year from June 2019 to May 2020. Patients of age >18 years, having hypothyroidism on treatment or newly diagnosed, and who gave written informed consent were included in the study. Patients with any of the following were excluded from the study: chronic kidney disease, nephrotic syndrome, drugs causing thyroid dysfunction, pregnancy, obvious airway abnormality, history of maxillofacial neck trauma and surgery, diagnosed neuromuscular disease, and patients ≤18 years of age.

Methodology

In this cross-sectional study, total 100 subjects were enrolled on the basis of inclusion and exclusion criteria from the indoor and outdoor patient department. Informed written consent was taken from all subjects after ethical clearance by the institutional ethical committee.

Patient evaluation

All enrolled patients underwent detailed clinical history and physical examination. Medical history was obtained with special emphasis on features of hypothyroidism such as excessive daytime sleepiness, lethargy, sleep quality, and cognitive deficits. Past history regarding the duration of hypothyroidism and treatment was taken (levothyroxine). Complete general physical and systemic examinations including anthropometric measurement (height, weight, neck circumference, waist circumference, and body mass index [BMI]) were done in all cases. After clinical evaluation, all patients were advised for routine investigations including complete hemogram, serum electrolytes (sodium and potassium), blood urea and serum creatinine, fasting lipid profile, fasting and postprandial blood sugar, glycated hemoglobin, and thyroid profile.

Thyroid profile

TSH and free T4 (FT4) concentrations were determined in clinical laboratory using sensitive radioimmunoassay techniques. The normal range for TSH and FT4 was 0.7–6.0 mU/mL and 0.6–1.8 ng/dl, respectively. To assess the prevalence of OSA, STOP-Bang questionnaire was used for screening purpose in each and every hypothyroidism patient enrolled in the study. The STOP-Bang questionnaire is an 8-item questionnaire, each item scored as 1. STOP-Bang questionnaire includes Snoring, Tiredness during daytime, Observed apnea, and high blood Pressure, BMI, Age, Neck circumference, and Gender (male). It has been shown that with a stepwise increase of the STOP-Bang score, the probability of OSA increases. The STOP-Bang questionnaire with a score ≥3 consistently demonstrated high sensitivity to detect OSA in different populations. In accordance with previous studies, we used a cutoff value of 3. Hypothyroidism patients with STOP-Bang score ≥3 were subjected for full-night polysomnography. All the patients had been seen by ENT specialists before they underwent polysomnography.

Polysomnography

Polysomnography was done in the Department of Medicine.

The Apnea–Hypopnea Index

It was calculated on the basis of polysomnography. AHI >5 was classified as OSA. These OSA patients were grouped into mild (5–14), moderate (15–30), and severe (>30) on the basis of AHI.

Statistical analysis

The statistical analysis was done using the Statistical Package for the Social Sciences version 21.0 Statistical Analysis Software. The values were represented in number (%) and mean ± SD. The level of significance “P” mentioned in the results was considered significant if P < 0.05.

Ethical clearance and funding

This study was approved by the institutional ethical committee and was not supported by any funding agency.


   Results Top


The present study population comprises a total of 100 hypothyroid patients either newly diagnosed or already taking levothyroxine and fulfilling the inclusion criteria. All the patients were subjected to the STOP-Bang questionnaire in order to select patients with intermediate to high risk of OSA (STOP-Bang ≥3). All 100 patients enrolled in the study had STOP-Bang score of ≥3 (51 cases [51%] had a score of 3–4 and 49 [49%] cases had a score of 5–8) and therefore all patients were subjected to polysomnography. Out of 100 patients, who underwent polysomnography, 26 (26%) cases had AHI <5 (non-OSA group) and 74 (74%) cases had AHI ≥5 (OSA group), as shown in [Table 1].
Table 1: Prevalence of obstructive sleep apnea in study population (n=100)

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Patients diagnosed with OSA were further classified into mild, moderate, and severe groups on the basis of severity. Out of total 74 OSA cases, 29 (39.2%) cases had mild OSA (AHI 5–14), 15 (20.3%) cases had moderate OSA (AHI 15–30), and 30 (40.5%) cases had severe OSA, as shown in [Table 2].
Table 2: Classification of obstructive sleep apnea cases (n=74)

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The age of the study population ranged between 24 and 78 years. The mean age of all the patients was 58.28 ± 11.22 years. The mean age of the patients in the OSA group (59.27 ± 11.17 years) was higher than the non-OSA group (55.46 ± 11.09 years). In the OSA group, patients with age >65 years were more (44.6%) in comparison with patients with age group 51–65 years (36.4%) and age group ≤50 years (18.9%). However, on statistical analysis, the association of age with OSA was not found to be significant (P = 0.588), as shown in [Table 3].
Table 3: Association of age with obstructive sleep apnea

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The severity of OSA was compared in the different age groups to study the association of age with severity of OSA. Patients with severe OSA had a mean age of 60.70 ± 9.84 years and were older as compared to patients with mild and moderate OSA having mean ages of 57.83 ± 13.19 years and 59.20 ± 9.68 years. The association of age with severity of OSA was not found to be statistically significant (P = 0.620), as shown in [Table 4].
Table 4: Association of age with severity of obstructive sleep apnea

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Out of 100 hypothyroid cases, 64 (64%) were male and 36 (36%) were female. The proportion of males was found to be higher than females in both the groups (P = 0.637). On comparing the association of gender with severity of OSA, we found that the proportion of male patients was high in all the three groups of severity, however, no statistically significant association was there between gender and severity of OSA (P = 0.977).

Further, we compared anthropometric parameters (weight, height, and BMI) between the two groups of patients with or without OSA and association of these parameters with the severity of OSA. The mean weight was 74.49 ± 10.53 kg in the OSA group and 73.04 ± 5.42 kg in the non-OSA group. The mean value of height was 157.35 ± 7.32 cm in the OSA group and 160.42 ± 7.23 cm in the non-OSA group. The mean value of BMI was 30.10 ± 3.60 kg/m2 in the OSA group and 28.46 ± 2.85 kg/m2 in the non-OSA group. BMI of the OSA group was found to be statistically higher as compared to that of the non-OSA group (P = 0.040), however, difference in weight and height of both the groups was found to be nonsignificant on statistical analysis, as shown in [Table 5].
Table 5: Association of anthropometric parameters in both groups

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The association of anthropometric parameters (weight, height, and BMI) with severity of OSA is shown in [Table 6]. The mean weight was 72.55 ± 9.88 kg, 72.33 ± 10.36 kg, and 77.44 ± 10.86 kg in mild, moderate, and severe OSA cases, respectively. Severe cases had a higher mean weight, but a statistically significant association was not seen (P = 0.138). The mean height was 157.55 ± 7.07 cm, 157.13 ± 8.40 cm, 157.27 ± 6.59 cm in mild, moderate, and severe OSA cases, respectively. However, a statistically significant association was not seen (P = 0.981). The mean value of BMI was 29.43 ± 3.31 kg/m2, 29.33 ± 3.71 kg/m2, and 31.12 ± 3.68 kg/m2 in mild, moderate, and severe OSA cases, respectively. The BMI was found to be higher in severe OSA, but it was statistically nonsignificant (P = 0.128).
Table 6: Association of anthropometric parameters and severity of obstructive sleep apnea

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Increasing trend in the OSA was observed with increasing BMI, however, this association was found to be nonsignificant on statistical analysis (P = 0.480) [Table 7]. Patients who were either overweight or obese had more number of moderate-to-severe OSA in comparison to patients with normal BMI. However, no statistically significant association was seen between severity of BMI and severity of OSA (P = 0.449) [Table 8].
Table 7: Association severity of obesity with obstructive sleep apnea

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Table 8: Association of severity of obesity with severity of obstructive sleep apnea

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We also studied the association of snoring and daytime sleepiness in the OSA and non-OSA groups. Snoring was observed in a higher proportion of the OSA group (98.6%) as compared to the non-OSA group (84.6%), which was statistically significant (P = 0.005). Similarly, a higher proportion of OSA patients (87.8%) with daytime sleepiness were found than non-OSA patients (38.5%), which showed a statistically significant association between OSA and daytime sleepiness (P < 0.001). We also studied the association of snoring and daytime sleepiness and severity of OSA. A higher proportion of patients with snoring were seen in all mild, moderate, and severe OSA groups (96.5%, 100%, and 100%) and were not statistically significant (P = 0.455). Similarly, a higher proportion of patients had daytime sleepiness in mild, moderate, and severe OSA groups (75.9%, 100%, and 93.3%), which was statistically significant (P = 0.03).

The mean value of FT4 was lower in the OSA group (3.34 ± 1.71 ng/dl) as compared with the non-OSA group (3.34 ± 1.71 ng/dl). No significant association was found between FT4 value and OSA (P = 0.376). The mean value of TSH was higher in the OSA group (12.55 ± 12.25 μU/mL) as compared with the non-OSA group (11.14 ± 18.85 μU/mL). No significant association was found between FT4 value and OSA (P = 0.663) [Table 9]. The association of FT4/TSH with severity of OSA was also studied, as mentioned in [Table 10]. The mean TSH value was more with increasing severity of OSA, but no significant association was found between TSH and OSA (P = 0.550).
Table 9: Association of thyroid profile with study population

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Table 10: Association of thyroid profile and severity of obstructive sleep apnea

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Out of 100 cases, 41 patients were treatment naïve with mean TSH value of 13.1 ± 7 and 59 were on treatment with mean TSH of 8.3 ± 4. Treatment-naïve patients had a statistically higher number of OSA cases in comparison to patients on treatment, as shown in [Table 11].
Table 11: Effect of treatment on obstructive sleep apnea in hypothyroidism

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   Discussion Top


In this study, a total of 100 hypothyroid patients were enrolled and all patients were subjected to overnight polysomnography after screening by STOP-Bang questionnaire. Out of 100 patients, 74 patients (74%) had OSA (AHI ≥5) and 26 patients (26%) had no OSA (AHI ≤5), so the prevalence of OSA in our study population was 74%. On the basis of AHI, the patients were further divided into mild, moderate, and severe OSA. Out of 74 OSA patients, 29 (39.2%) had mild OSA, 15 (20.3%) had moderate OSA, and 30 (40.5%) had severe OSA.

Previous studies have shown an incidence of OSA ranging from 25% to 82%. In particular, Grunstein et al. reported a very high prevalence (75%) of OSA in patients with unrecognized hypothyroidism, while Misiolek et al. showed that 5 (33%) patients had sleep apnea out of 15 hypothyroid patients.[8],[9] One more study by Jha et al. found a 30% association between OSA and hypothyroidism.[12] Hira et al. in their study found that 45% of hypothyroidism had OSA.[13] Mikelson et al. concluded that 40% of patients had OSA with hypothyroidism.[14] Lin CC et al. observed that 25% of hypothyroid patients had sleep apnea in their study.[15] One more study by Rajagopal et al. showed a strong association (82%) of OSA with hypothyroidism.[16]

The age of patients enrolled in the study ranged between 24 and 78 years and the mean age of patients was 58.28 ± 11.22 years. The mean age of OSA patients was 59.27 ± 11.17 years while that of non-OSA patients was 55.46 ± 11.09 years. The prevalence of OSA was increasing with increment in age of patients, but this difference was not found to be statistically significant. Our findings are consistent with the results of prior studies by Sharma et al., Franklin et al., and Deng et al. They found in their study that the prevalence of OSA increases with the age, though age is not an independent risk factor for OSA.[17],[18],[19]

Out of 100 hypothyroid cases enrolled in the study, 64 (64%) were male and the rest were female. The proportion of males was found to be higher in both the groups, but this difference was not found to be statistically significant. In a previous study of Lin et al., it was found that males had a higher AHI than females.[20]

In the present study, OSA seems to be associated with higher BMI. The mean value of BMI was higher in OSA patients than in non-OSA patients with statistically significant association. This was supported by the studies done by Sharma et al. and Franklin et al. They concluded that OSA is more common in the population with increasing obesity (in terms of higher BMI).[17],[18] The above association is also supported by studies of Grunstein et al.[10]

We found that snoring and daytime sleepiness were observed in higher proportion of OSA cases as compared to non-OSA cases, which was statistically significant. This was also found in a previous study done by Lindberg.[21]

We also tried to show the relationship between FT4 and TSH values with the prevalence of OSA. In our study, the mean FT4 was 3.34 ± 1.71 ng/dl in OSA and 3.70 ± 1.95 ng/dl in non-OSA, which was lower in the OSA group. It was observed that the association of FT4 with OSA was not found to be significant. Similarly, the mean TSH was 12.5 ± 12.25 μU/mL in OSA and 11.14 ± 18.85 μU/mL in non-OSA, which was higher in the OSA group than the non-OSA group, but no significant association was seen. Although the mean TSH value showed an incremental trend with increasing severity of OSA, it had shown no significant association between TSH and OSA on statistical analysis (P = 0.550). Sreedharan et al. showed a rare association of severe sleep apnea in an untreated hypothyroidism patient.[22]

When we classified the patients into two groups based on treatment, we had found that treatment-naïve patients had a statistically higher number of OSA cases in comparison to patients on treatment.

Limitations

Small sample size and cross-sectional design are limitations of our study. Hypothyroidism can lead to obesity, and obesity itself is a risk factor for OSA, therefore, it was a confounding factor in our study. Further follow-up studies of larger sample size are required to strengthen the association of hypothyroidism with OSA and also to see the effect of treatment on prevalence of OSA in hypothyroidism.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Full text]  



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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