Patterns of thyroid disorders among patients attending an endocrine clinic in Dhaka city

Authors

DOI:

Keywords

thyroid diseases, hypothyroidism, thyrotoxicosis, thyroiditis, Bangladesh 

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Correspondence

Md Rakibul-Hasan
Email: dr.mrh46@gmail.com

Publication history

Received: 6 Jan 2025
Accepted: 28 May 2025
Published online: 30 July 2025

Responsible editor

Reviewers

B: Anonymous
G: Anonymous

Funding

None

Ethical approval

Approved by IRB of Medical College for Women and Hospital (Memo No. MCW/Ethical committee/2024/12(1), Dated 29 Dec 2024). 

Trial registration number

Not applicable

Copyright

© The Author(s) 2025; all rights reserved. 
Published by Bangabandhu Sheikh Mujib Medical University (currently Bangladesh Medical University).
Abstract
Background: Data on the presentation patterns of thyroid disorders are almost lacking in Bangladesh. We present here the data of an Endocrine Outpatient Clinic based in Dhaka city.

Methods: We reviewed data from the electronic health records of an Endocrine Outpatient Clinic in Dhaka, Bangladesh, over a two-year period. Thyroid function status was interpreted according to the reference range of the corresponding laboratory and classified according to the International Classification of Diseases 11th Revision (ICD-11). 

Results: Among 3140 patients, 1015 (32.3%) had thyroid disorders. The age of patients with thyroid disorders ranged from 1 to 84 years, with a median age of 36.0 years (interquartile range: 28.0–48.0 years), and 802 (79.0%) were female. Hypothyroidism [overt hypothyroidism, n=568 (56.0%) and subclinical hypothyroidism, n=281 (27.7%)] was the most common thyroid disorder, followed by thyrotoxicosis (106; 10.4%). Graves’ disease (n=68; 6.7%) was the most common cause of thyrotoxicosis, followed by toxic multinodular goitre (n=12; 1.2%). Structural abnormalities with euthyroid status were present in 42 (4.1%) patients. Those with overt hypothyroidism had a higher age (38.0 vs. 34.0 years; P <0.001). Diabetes and hypertension were co-existent. Participants with nodular goitre had a higher mean age (47.1 versus 37.9 years; P =0.14 ).  

Conclusion: Thyroid disorders account for one-third of patients who attended an Endocrine Outpatient Clinic, with the predominance of overt hypothyroidism, followed by subclinical hypothyroidism, and thyrotoxicosis. 
Key messages
One-third of patients who attended the Endocrine Clinic in Dhaka city have thyroid disorders. There is a female predominance (79.0%) of among patients with thyroid disorders. The most common pattern is overt hypothyroidism (56.0%), followed by subclinical hypothyroidism (27.7%), Graves’ disease (6.7%), and structural abnormalities with euthyroid (4.1%) status.
Introduction
Nearly 200 million people worldwide are estimated to have thyroid disorders [1]. These issues are most often caused by iodine deficiency in areas where iodine is lacking, and by autoimmune thyroid conditions where iodine intake is sufficient. Surprisingly, one-third of the global population still lives in iodine-deficient regions [2]. In areas with enough iodine, hypothyroidism affects about 1% to 2% of people, while hyperthyroidism is seen in 0.2% to 1.3%. Moreover, the percentage of palpable thyroid nodules in the general population is 4% to 7% [3]. In Bangladesh, although the exact numbers are unknown, it's estimated that approximately 20% of the population may have some form of thyroid disorders but half of them are unaware of their condition [4]. Asymptomatic and mild cases are often neglected and out of medical attention. However, patients visiting specialised endocrine clinics usually have severe and complex problems, providing important insights into the challenges of diagnosing and managing these disorders. This study aimed  to understand the range of thyroid disorders seen at on Endocrine clinic. 

Groups based on pre-test marks

Pretest
marks (%)

Posttest

Marks (%)

Difference in pre and post-test marks (mean improvement)

P

Didactic lecture classes

<50%

36.6 (4.8)

63.2 (9.4)

26.6

<0.001

≥50%

52.8 (4.5)

72.4 (14.9)

19.6

<0.001

Flipped classes

<50%

36.9 (4.7)

82.2 (10.8)

45.4

<0.001

≥50%

52.8 (4.6)

84.2 (10.3)

31.4

<0.001

Data presented as mean (standard deviation)

Background characteristics

Number (%)

Age at presentation (weeks)a

14.3 (9.2)

Gestational age at birth (weeks)a

37.5 (2.8)

Birth weight (grams)a

2,975.0 (825.0)

Sex

 

Male

82 (41)

Female

118 (59)

Affected side

 

Right

140 (70)

Left

54 (27)

Bilateral

6 (3)

Delivery type

 

Normal vaginal delivery

152 (76)

Instrumental delivery

40 (20)

Cesarean section

8 (4)

Place of delivery

 

Home delivery by traditional birth attendant

30 (15)

Hospital delivery by midwife

120 (60)

Hospital delivery by doctor

50 (25)

Prolonged labor

136 (68)

Presentation

 

Cephalic

144 (72)

Breech

40 (20)

Transverse

16 (8)

Shoulder dystocia

136 (68)

Maternal diabetes

40 (20)

Maternal age (years)a

27.5 (6.8)

Parity of mother

 

Primipara

156 (78)

Multipara

156 (78)

aMean (standard deviation), all others are n (%)

Background characteristics

Number (%)

Age at presentation (weeks)a

14.3 (9.2)

Gestational age at birth (weeks)a

37.5 (2.8)

Birth weight (grams)a

2,975.0 (825.0)

Sex

 

Male

82 (41)

Female

118 (59)

Affected side

 

Right

140 (70)

Left

54 (27)

Bilateral

6 (3)

Delivery type

 

Normal vaginal delivery

152 (76)

Instrumental delivery

40 (20)

Cesarean section

8 (4)

Place of delivery

 

Home delivery by traditional birth attendant

30 (15)

Hospital delivery by midwife

120 (60)

Hospital delivery by doctor

50 (25)

Prolonged labor

136 (68)

Presentation

 

Cephalic

144 (72)

Breech

40 (20)

Transverse

16 (8)

Shoulder dystocia

136 (68)

Maternal diabetes

40 (20)

Maternal age (years)a

27.5 (6.8)

Parity of mother

 

Primipara

156 (78)

Multipara

156 (78)

aMean (standard deviation), all others are n (%)

Mean escape latency of acquisition day

Groups                 

NC

SC

ColC

Pre-SwE Exp

Post-SwE Exp

Days

 

 

 

 

 

1st

26.2 (2.3)

30.6 (2.4) 

60.0 (0.0)b

43.2 (1.8)b

43.8 (1.6)b

2nd

22.6 (1.0) 

25.4 (0.6)

58.9 (0.5)b

38.6 (2.0)b

40.5 (1.2)b

3rd

14.5 (1.8) 

18.9 (0.4) 

56.5 (1.2)b

34.2 (1.9)b 

33.8 (1.0)b

4th

13.1 (1.7) 

17.5 (0.8) 

53.9 (0.7)b

35.0 (1.6)b

34.9 (1.6)b

5th

13.0 (1.2) 

15.9 (0.7) 

51.7 (2.0)b

25.9 (0.7)b 

27.7 (0.9)b

6th

12.2 (1.0) 

13.3 (0.4) 

49.5 (2.0)b

16.8 (1.1)b

16.8 (0.8)b

Average of acquisition days

5th and 6th 

12.6 (0.2)

14.6 (0.8)

50.6 (0.7)b

20.4 (2.1)a

22.4 (3.2)a

NC indicates normal control; SC, Sham control; ColC, colchicine control; SwE, swimming exercise exposure.

aP <0.05; bP <0.01.

Categories

Number (%)

Sex

 

   Male

36 (60.0)

   Female

24 (40.0)

Age in yearsa

8.8 (4.2)

Education

 

   Pre-school

20 (33.3)

   Elementary school

24 (40.0)

   Junior high school

16 (26.7)

Cancer diagnoses

 

Acute lymphoblastic leukemia

33 (55)

Retinoblastoma

5 (8.3)

Acute myeloid leukemia

4 (6.7)

Non-Hodgkins lymphoma

4 (6.7)

Osteosarcoma

3 (5)

Hepatoblastoma

2 (3.3)

Lymphoma

2 (3.3)

Neuroblastoma

2 (3.3)

Medulloblastoma

1 (1.7)

Neurofibroma

1 (1.7)

Ovarian tumour

1 (1.7)

Pancreatic cancer

1 (1.7)

Rhabdomyosarcoma

1 (1.7)

aMean (standard deviation)

Narakas classification

Total

200 (100%)

Grade 1

72 (36%)

Grade 2

64 (32%)

Grade 3

50 (25%)

Grade 4

14 (7%)

Complete recoverya

107 (54)

60 (83)

40 (63)

7 (14)

-

Near complete functional recovery but partial deformitya

22 (11)

5 (7)

10 (16)

6 (12)

1 (7)

Partial recovery with gross functional defect    and deformity

31 (16)

7 (10)

13 (20)

10 (20)

1 (7)

No significant improvement 

40 (20)

-

1 (1.5)

27 (54)

12 (86)

aSatisfactory recovery

bGrade 1, C5, 6, 7 improvement; Grade 2, C5, 6, 7 improvement; Grade 3, panpalsy C5, 6, 7, 8, 9, Grade 4, panpalsy with Hornon’s syndrome.

Narakas classification

Total

200 (100%)

Grade-1

72 (36%)

Grade-2

64 (32%)

Grade-3

50 (25%)

Grade-4

14 (7%)

Complete recoverya

107 (54)

60 (83)

40 (63)

7 (14)

-

Near complete functional recovery but partial deformitya

22 (11)

5 (7)

10 (16)

6 (12)

1 (7)

Partial recovery with gross functional defect    and deformity

31 (16)

7 (10)

13 (20)

10 (20)

1 (7)

No significant improvement 

40 (20)

-

1 (1.5)

27 (54)

12 (86)

aSatisfactory recovery

bGrade 1, C5, 6, 7 improvement; Grade 2, C5, 6, 7 improvement; Grade 3, panpalsy C5, 6, 7,8,9, Grade 4, panpalsy with Hornon’s syndrome.

Variables in probe trial day

Groups

NC

SC

ColC

Pre-SwE Exp

Post-SwE Exp

Target crossings

8.0 (0.3)

7.3 (0.3) 

1.7 (0.2)a

6.0 (0.3)a

5.8 (0.4)a

Time spent in target

18.0 (0.4) 

16.2 (0.7) 

5.8 (0.8)a

15.3 (0.7)a

15.2 (0.9)a

NC indicates normal control; SC, Sham control; ColC, colchicine control; SwE, swimming exercise exposure.

aP <0.01.

Pain level

Number (%)

P

Pre

Post 1

Post 2

Mean (SD)a pain score

4.7 (1.9)

2.7 (1.6)

0.8 (1.1)

<0.001

Pain categories

    

   No pain (0)

-

1 (1.7)

31 (51.7)

<0.001

   Mild pain (1-3)

15 (25.0)

43 (70.0)

27 (45.0)

 

   Moderete pain (4-6)

37 (61.7)

15 (25.0)

2 (3.3)

 

   Severe pain (7-10)

8 (13.3)

2 (3.3)

-

 

aPain scores according to the visual analogue scale ranging from 0 to 10; SD indicates standard deviation

Surgeries

Number  

(%)

Satisfactory outcomes n (%)

Primary surgery (n=24)

 

 

Upper plexus

6 (25)

5 (83)

Pan-palsy

18 (75)

6 (33)

All

24 (100)

11 (46)

Secondary Surgery (n=26)

 

 

Shoulder deformity

15 (58)

13 (87)

Wrist and forearm deformity

11 (42)

6 (54)

All

26 (100)

19 (73)

Primary and secondary surgery

50 (100)

30 (60)

Mallet score 14 to 25 or Raimondi score 2-3 or Medical Research grading >3 to 5.

Narakas classification

Total

200 (100%)

Grade-1

72 (36%)

Grade-2

64 (32%)

Grade-3

50 (25%)

Grade-4

14 (7%)

Complete recoverya

107 (54)

60 (83)

40 (63)

7 (14)

-

Near complete functional recovery but partial deformitya

22 (11)

5 (7)

10 (16)

6 (12)

1 (7)

Partial recovery with gross functional defect    and deformity

31 (16)

7 (10)

13 (20)

10 (20)

1 (7)

No significant improvement 

40 (20)

-

1 (1.5)

27 (54)

12 (86)

aSatisfactory recovery

bGrade 1, C5, 6, 7 improvement; Grade 2, C5, 6, 7 improvement; Grade 3, panpalsy C5, 6, 7,8,9, Grade 4, panpalsy with Hornon’s syndrome.

Trials

Groups

NC

SC

ColC

Pre-SwE Exp

Post-SwE Exp

1

20.8 (0.6)

22.1 (1.8)

41.1 (1.3)b

31.9 (1.9)b

32.9 (1.8)a, b

2

10.9 (0.6)

14.9 (1.7)

37.4 (1.1)b

24.9 (2.0)b

26.8 (2.5)b

3

8.4 (0.5)

9.9 (2.0)

32.8 (1.2)b

22.0 (1.4)b

21.0 (1.4)b

4

7.8 (0.5)

10.4 (1.3)

27.6(1.1)b

12.8 (1.2)b

13.0 (1.4)b

Savings (%)c

47.7 (3.0)

33.0 (3.0)

10.0 (0.9)b

23.6 (2.7)b

18.9 (5.3)b

NC indicates normal control; SC, Sham control; ColC, colchicine control; SwE, swimming exercise exposure.

aP <0.05; bP <0.01.

cThe difference in latency scores between trials 1 and 2, expressed as the percentage of savings increased from trial 1 to trial 2

Methods
Study population
We have a specialised endocrinology outpatient clinic at Uttara, Dhaka, Bangladesh. The clinic keeps clinical and demographic details of the patients' electronic health records. We included all consecutive patients with any thyroid disorder who visited the clinic between 30 August 2022 and 15 December 2024. Of these, 1,015 patients (male and female) were identified as having thyroid disorders of any age. Among them, 217 (21.3%) patients with type 2 diabetes were reported elsewhere [5]. 

Classifications and diagnosis of thyroid disorders
The diagnosis of thyroid disorders was made either based on previous medical records or a recent investigation of thyroid function based on clinical presentations of the patients. Disorders of the thyroid gland were classified according to the ICD-11 for Mortality and Morbidity Statistics [6]. Estimation of TSH and FT4 was carried out using an indirect chemiluminescence method for newly diagnosed cases. For non-pregnant adults, a TSH range 0.35–5.5 µIU/mL, FT4: 0.78–2.19 ng/dL, and FT3: 2.30–4.20 pg/mL were considered normal. Thyroid ultrasonogram findings were used to define structural thyroid disease in suspected cases. In hyperthyroid patients, TSH receptor antibody (TRAb), thyroid scan, and radioactive iodine uptake were used as appropriate to differentiate Graves’ disease from other causes of thyrotoxicosis. We used the following criteria to diagnose different types of thyroid disorders in non-pregnant adults: 
  1. Subclinical hypothyroidism (SCH): FT4= 0.78–2.19 ng/dL and TSH =5.5 to <20.0 µIU/mL
  2. Overt primary hypothyroidism: FT4 <0.78 ng/dL and TSH =20.0 µIU/mL
  3. Secondary hypothyroidism: FT4 <0.78 ng/dL and TSH = undetectable to <20.0 µIU/mL
  4. Subclinical thyrotoxicosis: FT4 =0.78–2.19 ng/dL and TSH <0.35 µIU/mL
  5. Primary thyrotoxicosis: FT4 >2.19 ng/dL and TSH <0.35 µIU/mL
  6. Solitary thyroid nodule and multinodular goitre – diagnosed based on ultrasonogram and thyroid scan findings
  7. Thyroid malignancy- diagnosed by histopathology. In case of Pregnancy, children, and adolescents, specific laboratory values were used in this group of patients.
Statistical analysis
Data were analysed using SPSS software (version 25.0). Continuous variables were expressed as the mean ± standard deviation (SD), or median with interquartile range (IQR), depending on their distribution. Categorical variables were presented as numbers and percentages. 

Group

Didactic posttest marks (%)

Flipped posttest marks (%)

Difference in marks (mean improvement)

P

<50%

63.2 (9.4)

82.2 (10.8)

19.0

<0.001

≥50%

72.4 (14.9)

84.2 ( 10.3)

11.8

<0.001

Data presented as mean (standard deviation)

Results
We present the data of 1015 (32.3%) patients who had a functional or structural thyroid disorders. Table 1 shows the spectrum of thyroid disorders according to ICD-11. The predominant disorders were acquired hypothyroidism (83.7%), thyrotoxicosis with diffuse goitre (6.7%), and different types of nontoxic goitres (3.6%). Four patients had congenital hypothyroidism without goitre. Among 36 patients with nontoxic goitre, 14 had diffuse goitre, and the frequency of single and multinodular goitre was 11 for both. Sixteen patients presented with thyrotoxicosis; however, they were lost to follow-up.
 
Table 1 The type of thyroid disorders among patients attending an endocrine outpatient department according to International Classification of Diseases, 11th revision, ICD -11 (n= 1015)

ICD-11

Number (%)

5A00 Hypothyroidism (n=858)

 

5A00.0 Congenital hypothyroidism

 

5A00.01 Permanent congenital hypothyroidism without goitre

4 (0.4)

5A00.2 Acquired hypothyroidism (n=849)

 

5A00.2Y Other specified acquired hypothyroidism (Primary acquired hypothyroidism)

568 (56.0)

5A00.2Z Acquired hypothyroidism, unspecified (Subclinical hypothyroidism)

281 (27.7)

5A61.40 Acquired central hypothyroidism

5 (0.5)

5A01 Nontoxic goitre (n=36)

 

5A01.0 Nontoxic diffuse goitre

14 (1.4)

5A01.1 Nontoxic single thyroid nodule

11 (1.1)

5A01.2 Nontoxic multinodular goitre

11 (1.1)

5A02 Thyrotoxicosis (n=106)

 

5A02.0 Thyrotoxicosis with diffuse goitre (Graves’ disease)

68 (6.7)

5A02.1 Thyrotoxicosis with toxic single thyroid nodule

2 (0.2)

5A02.2 Thyrotoxicosis with toxic multinodular goitre

12 (1.2)

5A02.Y Other specified thyrotoxicosis (n=8)

 

Subclinical thyrotoxicosis

4 (0.4)

Gestational thyrotoxicosis (JB44.5)

4 (0.4)

5A02.Z Thyrotoxicosis, unspecified (Thyrotoxicosis under evaluation)

16 (1.6)

5A03 Thyroiditis (n=8)

 

5A03.1 Subacute thyroiditis          

8 (0.8)

JB44 Certain specified complications of the puerperium (n=1)

 

JB44.5 Postpartum thyroiditis

1 (0.1)

DA05 Cysts of oral or facial-neck region (n=1)

 

DA05.Y Other specified cysts of oral or facial-neck region (Thyroglossal duct cyst)

1 (0.1)

2D10 Malignant neoplasms of thyroid gland (n=5)

 

2D10.0 Follicular carcinoma of the thyroid gland

1 (0.1)

2D10.1 Papillary carcinoma of the thyroid gland

4 (0.4)

Total

1015

Eight patients had a diagnosis of subacute thyroiditis. Among five patients with malignant neoplasms, four had papillary carcinoma and one had follicular carcinoma of the thyroid. Uncommon disorders included subclinical thyrotoxicosis (n=4), gestational thyrotoxicosis (n=4), postpartum thyroiditis (n=1), and thyroglossal duct cyst (n=1), etc. The predominant etiologies of hypothyroidism were primary acquired hypothyroidism (n=568) and subclinical hypothyroidism (n=281).The median age of the subjects were 36 years (interquartile range,  28.0–48.0). Those with overt primary  hypothyroidism had higher age (P =0.002) as well as higher frequencies of diabetes (P =0.001) and hypertension (P <0.001) (Table 2).
 
Table 2 Number (%) of overt primary and subclinical hypothyroidism (n=849) 

Characteristics

Total

(n=849)

Overt primary

hypothyroidism

(n=568)

Subclinical hypothyroidism

(n=281)

P

Age, years

<18 years

54 (6.4)

26 (4.6)

28 (10.0)

0.002

≥18 years

795 (93.6)

542 (95.4)

253 (90.0)

 

Sex

Female

684 (80.6)

465 (81.9)

219 (77.9)

0.17

Male

165 (19.4)

103 (18.1)

62 (22.1)

 

Co-morbidities

Diabetes mellitus 

229 (27.0)

173 (30.5)

56 (19.9)

0.001

Hypertension

348 (41.0)

258 (45.4)

90 (32.0)

<0.001

The predominant causes of thyrotoxicosis were thyrotoxicosis with diffuse and nodular goitre (single or multiple). Participants with nodular goitre had a higher mean age and frequency of DM (P <0.04) than those with diffuse goitre with thyrotoxicosis (Table 3).
 
Table 3 Number (%) of goitre types (n=82)

Characteristics

All goitres

(n=82)

Diffuse goitres

(n=68)

Nodular goitres

(n=14)

P

Age, years

<18 years

2 (2.4)

2 (2.9)

0 (–)

0.99

≥18 years

80 (97.6)

66 (97.1)

14 (100.0)

 

Sex

Female

61 (74.4)

51 (75.0)

10 (71.4)

0.75

Male

21 (25.6)

17 (25.0)

4 (28.6)

 

Co-morbidities        

Diabetes mellitus 

21 (25.6)

14 (20.6)

7 (50.0)

0.04

Hypertension

30 (36.6)

26 (38.2)

4 (28.6)

0.49

Discussion
There is hardly any published database on thyroid disorders in Bangladesh. The dataset we present here is one of the few available. We believe that publication of other datasets would provide a broader evidence base for future use in generating hypotheses for further research. 

The most common thyroid disorder in the study population was acquired hypothyroidism, followed by thyrotoxicosis with diffuse goitre and various nontoxic goitre. These findings align with the global data, where acquired hypothyroidism remains the leading thyroid disorder. In general, hypothyroidism affects up to 5% of the general population, and over 99% of affected people suffer from acquired hypothyroidism. Iodine deficiency is the top cause of thyroid disorders worldwide. Yet, where iodine is sufficient, Hashimoto's thyroiditis (an autoimmune disease) is the most common cause of thyroid failure [7]. Primary acquired hypothyroidism (56%) was the most common thyroid issue in this analysis, with subclinical hypothyroidism (27.7%) also being a major contributor, highlighting the importance of detecting these often symptomless cases due to potential long-term risks. Missing data on several variables limits our effort to generate hypotheses, e.g., thyroid autoantibodies and iodine levels [8]. 

The data from Kerala, India, provides a contrasting picture, the most common type of thyroid disorder there is non-toxic multinodular goitre (48.5%), followed by hypothyroidism (18.1%) [9]. Development of nodular thyroid enlargement is multi-factorial; natural goitrogens, iodine deficiency, malnutrition, and genetic factors might contribute, and these factors probably differ from patient to patient and have geographical variation [10]. In our data, there was a relatively lower prevalence of thyrotoxicosis, including Graves' disease (diffuse goitre) and toxic multinodular goitre. The prevalence of goitre and iodine deficiency in Bangladesh has been considerably reduced over the last two decades due to the “Universal Salt Iodization Programme” and autoimmunity is currently the leading cause of thyroid disorders [4]. There is a paucity of patients with sub-acute thyroiditis, gestational thyrotoxicosis, and postpartum thyroiditis, all of which were relatively rare. Data from other outpatient endocrinology settings indicate that thyroid malignancies are relatively common [11]. 

Children predominantly presented with subclinical hypothyroidism. Hypothyroidism in children and adolescents has deleterious effects on physical growth, mental development, and school performance, which may lead to more investigations among this age group, which possibly could have contributed to more cases of undiagnosed subclinical hypothyroidism [12, 13]. Overt primary hypothyroid patients were found to be more likely to have diabetes and hypertension compared to subclinical hypothyroidism [14, 15]. Thyrotoxicosis patients with nodular goitre were predominantly older than thyrotoxicosis with diffuse goitre, which was a typical picture we are familiar with.

Limitation
The data are generated from a single outpatient clinic, which limits their generalisability. We couldn't classify hypothyroidism types due to a lack of autoantibody and urinary iodine data. There are some missing values to confirm the diagnosis. 

Conclusion
Our findings are valuable as the first large-scale report on thyroid disorders in Bangladesh, providing a foundation for future research. The one-third patients who seek services at the endocrine clinic have thyroid disorders. There is a predominance of overt hypothyroidism, following by subclinical hypothyroidism and thyrotoxicosis. 
Acknowledgements
None
Author contributions
Concept and design of the study: MRH, RS, SAM, MSM, MFA. Acquisition, analysis, and interpretation of data: MRH, RS, SAM, MSM. Manuscript drafting and revising it critically: MRH, MSM, MFA. Approval of the final version of the manuscript: MRH, RS, SAM, MSM, MFA. Guarantor accuracy and integrity of the work: MRH 
Conflict of interest
We do not have any conflict of interest.
Data availability statement
We confirm that the data supporting the findings of the study will be shared upon reasonable request. 
Supplementary file
None
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