The study protocol was approved by the ethics committee of the institution and written informed consent was obtained from all participants. Consecutive patients attending thyroid clinic of a tertiary health care centre in the western part of India, during April to August 2005, were clinically evaluated for the presence of MNG. They could be incidentally detected or may present for goitre. On enquiry some of them may have symptoms suggestive of UAO, but it was never a presenting symptom. Fifty nine apparently asymptomatic (may have vague symptoms) euthyroid patients were screened. There were 55 females and four males with age range of 23–63 years.
A single physician evaluated all subjects with detailed history and clinical examination. Special emphasis was given to elicit symptoms of UAO like cough, exertional dyspnoea, choking sensation, worsening of symptoms, or discomfort in any position and feeling of fullness in the neck or chest. Patients were examined for intrathoracic extension of goitre, Pemberton's sign, and vocal cord palsy by indirect laryngoscopy.
Total tri-iodothyronine (T3), total thyroxine (T4), thyroid stimulating hormone (TSH) and antimicrosomal antibodies were estimated for all participants. All euthyroid MNG patients were subjected to PFT after documentation of normal chest X-ray and electrocardiogram. Non contrast CT scan of the neck and chest was performed within 12 hours of PFT evaluation. All patients underwent fine needle aspiration cytology (FNAC) of the dominant nodules of the goitre.
Patients with obstructive symptoms due to thyromegaly, cardiac disease (detected by history, clinical examination, or electrocardiogram), uncontrolled hypertension, pulmonary disease (detected by history, clinical examination, chest X-ray, or PFT), vocal cord palsy (detected by indirect laryngoscopy), and evidence of malignancy on FNAC, chronic smokers, pregnant females, and those who could not perform PFT properly were excluded. Three patients were excluded on these grounds.
Thyroid function tests
Thyroid function tests were estimated using a solid phase, two site chemiluminescent enzyme labelled immunometric assay on Immulite 1000. Intra-assay CV for T3, T4, and TSH were 5.4-13.2%, 6.3-8.4%, and 4.5–13.8%, while inter assay CV were 7.7–15.6%, 6.7–9.8%, and 8.0–17.5%, respectively. Antimicrosomal antibody titre was estimated using a semi quantitative microtitre particle agglutination test for invitro diagnostic detection and titration of microsomal antibodies in human serum. A titre of ≥1:100 was considered to be reactive.
Pulmonary function tests
Upper airway obstruction was defined based on the following parameters in PFT[6
- Forced inspiratory flow (FIF) rate at 50% of vital capacity (VC)
FIF 50% VC≤ 100 l/mt (≤ 1.67 l /s)
- Forced expiratory volume during the first second
(FEV1): Peak expiratory flow (PEF)
FEV1: PEF ≥ 8 ml/l/mt (≥0.48 l/l/s)
- Forced expiratory flow (FEF) rate at 50% of vital capacity: Forced inspiratory flow rate at 50% of vital capacity
FEF 50% VC: FIF 50% VC >1 for extra thoracic obstruction
FEF 50% VC: FIF 50% VC <1 for intra thoracic obstruction
- FEV during the first second: FEV during first 0.5 second (FEV 0.5)
FEV1: FEV 0.5 ≥1.5
- Inspection of the flow volume loop.
The subjects were diagnosed to have UAO if any one of the following combination of PFT parameters were present:
- Two separate parameters, which used flow rates at 50% of vital capacity were suggestive of UAO (combination of 1 and 3) OR
- Any one ratio which used volume was suggestive of UAO (2 or 4) OR
- The flow volume loop was showing inspiratory plateau and FEF 50% VC: FIF 50% VC >1 (variable extra thoracic obstruction) or the flow volume loop was showing expiratory plateau and the FEF 50% VC: FIF 50% VC <1 (variable intra thoracic obstruction) or flow volume loop was showing expiratory and inspiratory plateau (fixed obstruction).
Pulmonary function tests were performed using Master Screen Pneumo Machine from Jaeger (Master Pneumo Version 0.4 X) according to American Thoracic guidelines and standards,[9
] and FIF 50% VC, FEF 50% VC, FEV1, FEV 0.5, and PEF were measured. Flow volume loops were also obtained. The values were recorded as absolute value measured and percentage predicted with respect to their age, sex, weight, height using Udwadia standards.[11
] Pulmonary function tests were carried out by a qualified technician and reported by an experienced pulmonologist.
Non contrast computerised tomography scan
Contiguous axial plain CT scan images of supra and infra hyoid neck up to the carina were obtained using a Volume Zoom Siemens CT scan. The scan parameters included a slice thickness of five mm, table feed of 5-6 mm/s, scan time of 32 seconds, 120 KV, and 165 mA. Evaluation of the thyroid volume was performed on Siemens Workstation [Wizard]. Hounsfield unit of the thyroid was obtained. On each axial section the cross sectional area of the thyroid was measured by manually mapping the outer contours on the scanner's screen using a mouse controlled cursor with no inter slice gap. The data was fed to the software, which calculated the volume of the goitre.
Smallest tracheal cross sectional areas inside the goitre in deep inspiration, deep expiration and in functional residual capacity were obtained and the smallest of the three area was selected. The area was measured manually by outlining the outer counters of the tracheal air column. Smallest of the three areas was compared with the area of the trachea 2 cm above the carina to obtain a ratio. The area 2 cm above the carina was taken as the reference area because this area did not vary more than 10% from the area in the middle part of the trachea.[12
] In addition, the trachea at the level of two cm above the carina was always at maximum distance from the narrowed area. This ratio was calculated to denote the degree of tracheal narrowing.[8
] The tracheal narrowing was defined to be significant if the ratio was less than 50%.[14
] The thyroid volume and the tracheal area were calculated by a qualified radiologist.
Statistical analysis was done with SPSS version 16. Clinical features of patients with and without UAO proven on PFT were analyzed using paired t-test, while PFT parameters in symptomatic and asymptomatic patients were analyzed by Chi square test. Fisher's exact test was used to analyze clinical features and PFT parameters of patients with and without significant tracheal narrowing on CT scan. P value of <0.05 was considered to be significant.