|Year : 2017 | Volume
| Issue : 2 | Page : 63-70
Prevalence of hypothyroidism in Assam: A clinic-based observational study
Anindita Mahanta1, Sushmita Choudhury2, Sarojini Dutta Choudhury3
1 Department of Physiology, Gauhati Medical College, Guwahati, Assam, India
2 Department of Pulmonary Medicine, Tezpur Medical College, Tezpur, Assam, India
3 (Retd.) Department of Endocrinology, Gauhati Medical College, Guwahati, Assam, India
|Date of Web Publication||26-May-2017|
Department of Physiology, Gauhati Medical College, Guwahati - 781 032, Assam
Source of Support: None, Conflict of Interest: None
Introduction: Hypothyroidism is a common functional disorder of the thyroid gland. Despite extensive research, data on this subject are lacking from the northeastern part of India, which falls in the Sub-Himalayan goitrogenic belt. Therefore, we decided to study the profile of hypothyroidism in Assam, a northeastern state with the following objectives: to determine the prevalence of hypothyroidism and to describe the various modes of clinical presentation.
Materials and Methods: The study was conducted at a clinic-cum-radioimmunoassay laboratory in Guwahati, Assam, from January to November 2011. Two thousand and four hundred fifty-six patients referred to our center from different parts of Assam were evaluated clinically and their thyroid profile was estimated. Antithyroid peroxidase (TPO) antibody was estimated in 1950 patients.
Results: The prevalence of overt hypothyroidism was 10.9% (n = 267) and that of subclinical hypothyroidism was 13.1% (n = 321). Male:female ratio was 1:3. Among the cases of overt hypothyroidism, 247 (92.51%) were adult hypothyroids, 15 (5.62%) juvenile hypothyroids, and 5 (1.87%) cretins. The common presenting features of hypothyroidism were weakness (98%), lethargy (95%), dry and coarse skin (87%), and body ache (85%). Uncommon modes of presentation were pleural and pericardial effusion, low body weight, frequent motions, and palpitations. Postthyroidectomy and drug-induced hypothyroidism accounted for 2.38% cases each and postpartum hypothyroidism for 3.74% cases. Thirteen percent cases presented with goiter. The prevalence of anti-TPO antibody in the study population was 8.41%.
Conclusion: Hypothyroidsm is no longer a rarity, and Assam is no exception to this phenomenon. A population-based epidemiological study of thyroid disorders in Northeast India is an urgent need.
Keywords: Antithyroid peroxidase, goiter, hypothyroidism, thyroid disorder
|How to cite this article:|
Mahanta A, Choudhury S, Choudhury SD. Prevalence of hypothyroidism in Assam: A clinic-based observational study. Thyroid Res Pract 2017;14:63-70
|How to cite this URL:|
Mahanta A, Choudhury S, Choudhury SD. Prevalence of hypothyroidism in Assam: A clinic-based observational study. Thyroid Res Pract [serial online] 2017 [cited 2018 Oct 20];14:63-70. Available from: http://www.thetrp.net/text.asp?2017/14/2/63/207135
| Introduction|| |
Among various endocrine problems, thyroid disorders are the most common worldwide. It has been reported that in India alone, about 42 million people suffer from thyroid disorders. Worldwide, iodine deficiency is the most common cause of hypothyroidism. As the northeastern part of India is situated in the Sub-Himalayan goitrogenic belt, hypofunction of the thyroid gland is expected to be a common problem among the general population. Clinically, hypothyroidism is a syndrome manifested by a collection of symptoms and signs. They are influenced by the age of the patient, the rate at which the hypothyroidism develops and the presence of other disorders. In very young infants, hypothyroidism can result in irreversible mental and physical retardation, unless treatment is initiated within weeks after birth, whereas, in children and adults, the effects of hypofunction of thyroid though profound are reversible.
Since the syndrome of myxedema was described more than a century ago, the criteria for the diagnosis of hypothyroidism have evolved from clinical observation to bioassays, increasingly specific measurements of thyroid hormones in serum and quantitation of endogenous thyrotropin (thyroid-stimulating hormone [TSH]) production. An accurate diagnosis of hypothyroidism requires awareness of the clinical features that define a patients risk for thyroid hormone deficiency and proper use of the two tests usually required to confirm the disorder: serum TSH and free thyroxine (T4) assays. With the increasing use of thyroid hormone assays, many more subclinical cases have been detected. Measurement of antithyroid antibody helps to confirm the diagnosis of lymphocytic thyroiditis and aids in the prediction, of which patient with mild failure will progress to overt hypothyroidism.
Hypothyroidism may be overt or subclinical. Overt hypothyroidism is defined as high serum TSH concentrations and low serum free T4 concentrations, subclinical hypothyroidism is defined as high serum TSH (usually <10 mU/L) and normal serum free T4 concentrations. The prevalence of hypothyroidism increases with age and is nearly 10 times more common in females than in males. The prevalence and incidence of hypothyroidism are variable because existing studies have differed significantly in regard to population age range, geographic location, environmental factors such as dietary iodine and goitrogen intake, genetic characteristics of study population, and criteria used to define presence and degree of thyroid failure. Various large population-based screening studies have reported the prevalence of overt hypothyroidism to be around 1%–3%.,,
Subclinical hypothyroidism is much more prevalent having been found in 4%–10% in multiple populations.,,,,,,,,,, The Colorado Thyroid Disease Prevalence Study of 25,862 state residents reported an elevated serum TSH concentration in 9.5% of all subjects and in 8.9% of those who were not already taking thyroid hormone; nearly 75% of these individuals had serum TSH values between 5 and 10 mU/L and more than 95% had normal serum total T4 levels. The National Health and Nutritional Examination Survey III screened 17,353 adults and children in the United States and found elevated serum TSH levels (>4.5 mU/L) in 1.4%–8.1%.
In India, a population-based study done in Cochin  on 971 adult subjects estimated the prevalence of hypothyroidism to be 3.9% and that of subclinical hypothyroidism to be 9.4%. In women, the prevalence was higher (11.4%), whereas it was 6.2% in men. The prevalence of subclinical hypothyroidism increased with age. About 53% of the subjects with subclinical hypothyroidism were positive for antithyroid peroxidase (TPO) antibodies. In this study, urinary iodine status was studied in 954 subjects; the median value was 211 μg/L. This suggested that this population was iodine-sufficient. Unnikrishnan et al. conducted an epidemiological study in eight cities in India and found a high prevalence of hypothyroidism (10.95%), affecting approximately 1 in 10 adults in the population. Female gender and older age were found to be associated significantly with hypothyroidism. About 8.02% of the study population were found to have subclinical hypothyroidism. Among all cities, Kolkata recorded the highest prevalence of hypothyroidism (21.67%) while others showed comparable rates ranging from 8.88% (Hyderabad) to 11.07% (Delhi). Cities located in the inland regions of India (Delhi, Ahmedabad, Kolkata, Bengaluru, and Hyderabad) reported a significantly higher prevalence of hypothyroidism (11.73%) than those (Mumbai, Chennai, and Goa) in the coastal areas (9.45%).
Progression from subclinical to overt hypothyroidism has been reported to occur in 5%–18% of patients per year.,,,,, Individuals most likely to undergo progression are those with higher initial serum TSH levels, positive antithyroid antibodies, and a prior history of radio-iodine or external beam radiation therapy.,, On the other hand, individuals with minimal TSH elevation may remain stable for years without developing overt hypothyroidism ,,, and up to 37% may have their TSH values return to within population reference range.,
Although there has been a lot of research work on hypothyroidism, few papers on this subject have been published from the northeastern region of India. Assam, being a part of the Sub-Himalayan goitrogenic belt, deserves a discussion on this problem of public health importance. As there is a radioimmunoassay (RIA) laboratory in Guwahati, Assam approved by the Bhabha Atomic Research Centre, Mumbai where many patients are referred to/from different parts of Northeast India for evaluation of thyroid functions, therefore, we took the opportunity to carry out this referral clinic-based registry study with the following objectives:
- To find out the prevalence of hypothyroidism
- To describe the various modes of clinical presentations in hypothyroidism.
| Materials and Methods|| |
This referral clinic-based registry study was designed as a cross-sectional observational study. The study was conducted at a clinic-cum-RIA laboratory in Guwahati, Assam, India. The study period was from January 1 to November 30, 2011. During the study, 2456 patients were evaluated clinically and their thyroid profile was estimated. This included 14 cases of drug-induced hypothyroidism (hyperthyroid patients treated with antithyroid drugs) and 14 cases of postthyroidectomy hypothyroidism. Known hypothyroid patients on T4 treatment were not included in the study. Patients with a history of thyrotropic medications were also excluded from the study.
Serum total T3 and total T4 were measured by RIAK 4/4A and RIAK5/5A kits, respectively, by RIA method. The kits were obtained from Bhabha Atomic Research Centre, Mumbai, India. Serum TSH was measured by immunoradiometric assay. The sensitivity of the T3 assay was 0.22 ng/ml that of T4 was 0.5 μ/dl and for TSH was 0.016 μIU/ml. Of the total 2456 samples, anti-TPO antibody levels were measured in 1950 samples by RIA method using the anti-TPO kit obtained from M/S Beckman Coulter through Anand Brothers, New Delhi, India.
The reference values of our laboratory were 0.7–2.0 ng/ml for serum T3, 5.5–13.5 μg/dl for serum T4 and 0.3–5.0 μIU/ml for serum TSH. Patients with serum TSH >5.0 μIU/ml and serum T4 <5.5 μg/dl were diagnosed as overt hypothyroidism, and those with serum TSH >5.0 μIU/ml with serum T4 and T3 being within the normal reference level were diagnosed as subclinical hypothyroidism. Anti-TPO antibody was taken to be positive when the value was >12 IU/ml.
The values of serum TSH, T3, and T4 were expressed as mean ± standard deviation. The various modes of clinical presentation were expressed as the total number of patients presenting with a particular presenting feature and then calculated as a percentage of the total number of patients. All statistical analysis was done using Microsoft Office Excel (Windows 7).
| Results|| |
Out of the 2456 samples analyzed, frank or overt hypothyroidism was detected in 267 (10.9%) samples and subclinical hypothyroidism in 321 (13.1%) samples. [Figure 1] shows the breakup of the study population according to thyroid status. Out of the total 588 hypothyroid cases (overt as well as subclinical), 147 (25%) were male, and 441 (75%) were female, giving a male:female (M:F) ratio of 1:3. [Figure 2] shows the breakup of different types of overt hypothyroidism as observed in the present study. [Table 1] shows the age and sex distribution of all the cases of hypothyroidism (overt and subclinical, n = 588).
The most common presenting clinical feature of hypothyroidism in the present study was weakness (98%), followed by lethargy (95%), and dry and coarse skin (87%). Less common presenting clinical features were protrusion of tongue and primary amenorrhea with galactorrhea (2 cases each, 0.34%), umbilical hernia (4 cases, 0.68%), delayed milestones (10 cases, 1.7%), mental retardation (11 cases, 1.8%), and stunted growth (12 cases, 2%). Among these patients, there were 22 cases (3.74%) of postpartum hypothyroidism and 14 cases each (2.38%) of postthyroidectomy and drug-induced hypothyroidism. Thirteen percent cases presented with goiter (n = 77).
Among the subclinical hypothyroids, the most common clinical feature was body ache (80%), followed by fatigue (77%), and general weakness (75%). Uncommon modes of presentation observed in the present study were pleural and pericardial effusion (2 cases each, 0.34%), low body weight (52%), frequent motions (24%), and palpitations (41%).
[Table 2] shows the thyroid hormone profile of the 2456 cases included in the present study. This includes 1868 euthyroid cases, 321 subclinical hypothyroids, and 267 cases of overt hypothyroidism.
Anti-TPO antibody was found to be positive in 164 out of 1950 samples tested, giving a prevalence of 8.41%.
In the present study, among the 588 cases of hypothyroidism, 238 (40.48%) had hemoglobin value >11 g/dl, 305 (51.87%) had values between 9 and 11 g/dl, and 45 (7.65%) had values <9 g/dl. The total cholesterol level was <250 mg% in 324 cases (55%), between 250 and 350 mg% in 132 cases (22%), and >350 mg% in 132 cases (22%).
| Discussion|| |
In the present study, out of the 2456 samples analyzed, overt or frank hypothyroidism was detected in 267 cases (10.9%) and subclinical hypothyroidism in 321 cases (13.1%). The high prevalence of overt hypothyroidism as found in the present study is probably due to referral bias as this is a referral clinic-based registry study; hence, this figure may be higher than the actual prevalence in the general population. In an epidemiological study conducted in eight cities of India, Unnikrishnan et al. reported the overall prevalence of hypothyroidism to be 10.95%, which included 7.48% self-reported hypothyroidism and that of subclinical hypothyroidism to be 8.02%. Self-reported hypothyroidism has not been included as a separate entity in the present study. A study conducted in Mumbai by Deshmukh et al. found the prevalence of subclinical hypothyroidism to be 11.3%. Hak et al. reported a prevalence of 10.8% for subclinical hypothyroidism.
The present study found a female preponderance among the cases of both overt as well as subclinical hypothyroidism, with a M:F ratio of 1:3 for hypothyroid cases (both overt and subclinical) and 1:3.79 for subclinical hypothyroidism. Takashi et al. reported a M:F ratio of 1:6 for hypothyroidism, which is higher than that found in the present study, whereas John et al. reported the ratio to be 1:4, which is comparable to the present study. Deshmukh et al. reported a M:F ratio of 1:3.7 for subclinical hypothyroidism, which is comparable to the present study.
The present study found that the prevalence of hypothyroidism overall as well as subclinical cases were maximum in the age group of 55–64 years. Minimum prevalence was noted in the age-group of 2–12 years for hypothyroidism overall and 13–24 years for subclinical hypothyroidism. Unnikrishnan et al. reported that the prevalence of overt hypothyroidism was highest in the age group of 46–54 years and lowest in the age-group of 18–24 years whereas subclinical hypothyroidism was most prevalent in the age group of >55 years and least prevalent in the age-group of 18–24 years.
The most common presenting clinical features of hypothyroidism in the present study are weakness (98%), lethargy (95%) and dry, coarse skin (87%). [Table 3] compares the common presenting clinical features of the present study with that of early and recent studies. Among the cases of subclinical hypothyroidism, the most common symptoms were body ache 80%, fatigue 77%, and general weakness 75%. [Table 4] compares the common symptoms of subclinical hypothyroidism found in the present study with those reported by other authors.
Our study found the prevalence of anti-TPO positivity to be 8.41%, which is quite low compared to other studies. Iodine deficiency could be an underlying etiological factor for the low anti-TPO positivity and data on urinary iodide levels of the study population may offer an interesting insight. Iodine has been incriminated in inducing or precipitating thyroid autoimmunity. This is based on animal studies suggesting a strong relationship between iodine intake and development of autoimmune thyroiditis.,,, In addition, epidemiological studies suggest that autoimmune thyroiditis is more common in areas with adequate iodine intake rather than in iodine-deficient areas.,, On the other hand, some studies have not confirmed the above relationship., This discrepancy is not only due to the different populations examined but also due to the different interpretation of result in each study. Deshmukh et al. found anti-TPO positive in 23.6% euthyroid population and in 47.6% of subclinical hypothyroids. Unnikrishnan et al. reported anti-TPO positivity in 21.8% of the study population. Among the eight cities of India, which they surveyed, lowest prevalence of anti-TPO antibody was seen in Ahmedabad (13.26%) and highest prevalence was in Chennai (25.81%). Females showed greater prevalence of anti-TPO antibody compared to males (26.04% vs. 16.81%).
Postpartum hypothyroidism was reported in 3.7% cases in the present study. Noboyuku et al. and Lervang et al. have reported a lower prevalence of 2.5% and 1.8%, respectively, whereas Carlé et al. has reported a higher prevalence (4.7%). Hypothyroidism was found in 2.38% of postthyroidectomy cases in the present study as opposed to 1.8% cases in a Danish population reported by Carlé et al. and 5% cases reported by Chetri.
Thirteen percent cases presented with goiter in the present study compared to 11.5% reported by Takashi et al. and 12.5% by Goslings et al. Recent population studies have shown that 12% of adults have a palpable goiter. Endemic goiter has been reported from all over the country and not just from the Himalayan and Sub-Himalayan region. Researchers from New Delhi have shown that this was linked to iodine deficiency and this has resulted in decompensated hypothyroidism in many cases. This led to landmark studies which showed that iodine deficiency was associated with hypothyroidism in neonates, setting the scene for the salt iodization program. In the postiodization era, a study of 14,762 children from all over India found that 23% subjects had a goiter with a significantly higher level of median urinary thiocyanate excretion compared with controls, suggesting that despite iodization, the prevalence of goiter has not dramatically declined.
About 2.5% cases presented with hypothyroidism following treatment with antithyroid drugs in the present study. A lower prevalence has been reported by both Carlé et al. (1.6%) and Chetri  (1.06%). Two cases presented with galactorrhea and primary amenorrhea. Highly variable incidence of hyperprolactinemia (5%–39%) has been reported in cases of untreated primary hypothyroidism by Honbo et al. and Seshadri et al. The high incidence in other studies may be due to the fact that they were female-oriented studies. Kumkum. stated that amenorrhea occurs in hypothyroidism due to hyperprolactinemia, which results from a defect in the positive feedback of estrogen on luteinizing hormone (LH) and because of the suppression of LH and follicle-stimulating hormone. Clinical and experimental studies have suggested a close relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-ovarian axis. The influence of estrogen at higher levels of the HPT axis seems to integrate the reciprocal relationship between these two major endocrine axes.
The present study found pleural and pericardial effusion as a mode of presentation (two cases each). Pleural and pericardial effusion is a rare complication of severe hypothyroidism in children but can be present in 10%–30% adults. Martinez-Soto et al. reported six cases of pericardial effusion in children with severe hypothyroidism. The effusions resolved completely in 2–12 months after initiation of T4 replacement. Hypothyroidism should be considered in any child with unexplained pleural or pericardial effusion. Thirone et al. also reported a case of massive pericardial effusion as initial manifestation of hypothyroidism in a 21-year-old female patient. Therapy with levo-T4 resulted in clinical improvement without pericardiocentesis. Koo et al. have reported a chylous pleural effusion in a 37-year-old woman with severe hypothyroidism who improved after thyroid hormone replacement therapy. Martí et al. reported the case of a 43-year-old female who was diagnosed with hypothyroidism and presented with bilateral pleural effusion and a massive pericardial effusion, both of which regressed following thyroid hormone substitution. Gottehrer et al. reviewed the medical records of 128 patients with hypothyroidism and found that majority of effusions in patients with hypothyroidism were due to other causes. However, effusions solely due to hypothyroidism appeared to be a real entity. These effusions were borderline between exudates and transudates and showed little evidence of inflammation.
The unusual features observed in the present study were low body weight, frequent motions, and palpitations, observed in 52%, 77%, and 41% subclinical hypothyroidism cases, respectively. Our patients with unusual symptoms were referred to our center by either gastroenterologists or psychiatrists. Gastroenterologists diagnosed the cases with frequent motions as irritable bowel syndrome. The patients responded well with institution of T4 therapy. The occurrence of psychological and cognitive changes in adults with primary hypothyroidism was first described in the late 19th century., These early reports described myxedematous patients with a wide range of mental disturbances, from mild irritability to melancholia or “myxedematous madness.” In the present study, 45% cases of subclinical hypothyroidism reported feeling depressed.
Anemia (hemoglobin values <11 g/dl) was evident in about 60% cases, of which about 8% cases had severe anemia, and 52% cases had mild to moderate anemia. Das et al. have also reported similar findings. Nekrasova et al. reported anemia in 28.3% of subclinical hypothyroidism cases as compared to 11.1% in controls.
The present study had a short duration. Furthermore, being a cross-sectional type of observational study, no follow-up of the study participants was done. In addition, anti-TPO antibody status was not estimated in all the study participants. Moreover, being a referral clinic-based registry study, the study results are subject to referral bias, which may account for the high prevalence of overt hypothyroidism found in our study.
| Conclusion|| |
The present study was carried out to find out the prevalence of hypothyroidism, modes of clinical presentation, biochemical profile, and thyroid hormone profile among the patients attending a referral clinic in the northeastern state of Assam. The present study found a high prevalence of both overt and subclinical hypothyroidism, which could be due to referral bias. Majority of the overt hypothyroidism cases were of adult hypothyroidism, with cretins (untreated cases of congenital hypothyroidism presenting with mental retardation) being the least. The study found a low prevalence of anti-TPO antibody, which could be due to iodine deficiency and warrants a further study of the urinary iodide levels of the study population. In view of the findings of the present study and keeping in mind its limitations, a long-term population-based follow-up study of thyroid disorders in the northeast region of India is the need of the hour.
The authors are grateful to the technical staff of the radioimmunoassay laboratory, NL Medicare and Research Institute for their help during the study. The authors also acknowledge the cooperation of the patients who participated in the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kochupillai N. Clinical endocrinology in India. Curr Sci 2000;79:1061-7.
Braverman LE, Cooper DS, editors. Introduction to hypothyroidism. In: Werner and Ingbar's the Thyroid: A Fundamental and Clinical Text. Wolters Kluwer (India) Pvt. Ltd., New Delhi, Lippincott, Willams and Wilkins; 2013. p. 523.
Ladenson PW. Diagnosis of hypothyroidism. In: Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. Wolters Kluwer (India) Pvt. Ltd., New Delhi: Lippincott, Williams and Wilkins; 2013. p. 526.
Flynn RW, MacDonald TM, Morris AD, Jung RT, Leese GP. The thyroid epidemiology, audit, and research study: Thyroid dysfunction in the general population. J Clin Endocrinol Metab 2004;89:3879-84.
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al.
The spectrum of thyroid disease in a community: The Whickham survey. Clin Endocrinol (Oxf) 1977;7:481-93.
Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: An update. American College of Physicians. Ann Intern Med 1998;129:144-58.
Ross DC. Subclinical hypothyroidism. In: Bravermen LE, Utiger RD, editors. Werner and Ingbar's the Thyroid. 7th
ed. Philadelphia, PA: Lippencott-Raven; 1996. p. 1010-105.
Bagchi N, Brown TR, Parish RF. Thyroid dysfunction in adults over age 55 years. A study in an urban US community. Arch Intern Med 1990;150:785-7.
Geul KW, van Sluisveld IL, Grobbee DE, Docter R, de Bruyn AM, Hooykaas H, et al.
The importance of thyroid microsomal antibodies in the development of elevated serum TSH in middle-aged women: Associations with serum lipids. Clin Endocrinol (Oxf) 1993;39:275-80.
Sawin CT, Chopra D, Azizi F, Mannix JE, Bacharach P. The aging thyroid. Increased prevalence of elevated serum thyrotropin levels in the elderly. JAMA 1979;242:247-50.
Rosenthal MJ, Hunt WC, Garry PJ, Goodwin JS. Thyroid failure in the elderly. Microsomal antibodies as discriminant for therapy. JAMA 1987;258:209-13.
Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991;34:77-83.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al.
Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-99.
Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine sufficient adult South Indian population. J Indian Med Assoc 2009;107:72-7.
Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari N. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013;17:647-52.
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al.
The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham survey. Clin Endocrinol (Oxf) 1995;43:55-68.
Tunbridge WM, Brewis M, French JM, Appleton D, Bird T, Clark F, et al.
Natural history of autoimmune thyroiditis. Br Med J (Clin Res Ed) 1981;282:258-62.
Kabadi UM. Subclinical hypothyroidism. Natural course of the syndrome during a prolonged follow-up study. Arch Intern Med 1993;153:957-61.
Huber G, Staub JJ, Meier C, Mitrache C, Guglielmetti M, Huber P, et al.
Prospective study of the spontaneous course of subclinical hypothyroidism: Prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002;87:3221-6.
Díez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: An analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab 2004;89:4890-7.
Díez JJ, Iglesias P, Burman KD. Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 2005;90:4124-7.
Meyerovitch J, Rotman-Pikielny P, Sherf M, Battat E, Levy Y, Surks MI. Serum thyrotropin measurements in the community: Five-year follow-up in a large network of primary care physicians. Arch Intern Med 2007;167:1533-8.
Deshmukh V, Behl A, Iyer V, Joshi H, Dholye JP, Varthakavi PK. Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai. Indian J Endocrinol Metab 2013;17:454-9.
Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam study. Ann Intern Med 2000;132:270-8.
Takashi Y, Tomomichi T, Kenji I, Yaichiro Y, Masanobu K. Volume of Sella Turcica in normal subjects and in patients with primary hypothyroidism and hyperthyroidism. J Clin Endocrinol Metab 1976;42:817-22.
John L, Kangasabapathy AS, Koshi G, Koshi TS. Comparison of clinical profile with various laboratory tests in thyroid disorders. JAPI 1979;27:137-41.
Papanastasiou L, Vatalas IA, Koutras DA, Mastorakos G. Thyroid autoimmunity in the current iodine environment. Thyroid 2007;17:729-39.
Bagchi N, Brown TR, Urdanivia E, Sundick RS. Induction of autoimmune thyroiditis in chickens by dietary iodine. Science 1985;230:325-7.
Allen EM, Appel MC, Braverman LE. The effect of iodide ingestion on the development of spontaneous lymphocytic thyroiditis in the diabetes-prone BB/W rat. Endocrinology 1986;118:1977-81.
Mooij P, de Wit HJ, Bloot AM, Wilders-Truschnig MM, Drexhage HA. Iodine deficiency induces thyroid autoimmune reactivity in Wistar rats. Endocrinology 1993;133:1197-204.
Rasooly L, Burek CL, Rose NR. Iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. Clin Immunol Immunopathol 1996;81:287-92.
Furszyfer J, Kurland LT, McConahey WM, Woolner LB, Elveback LR. Epidemiologic aspects of Hashimoto's thyroiditis and Graves' disease in Rochester, Minnesota (1935-1967), with special reference to temporal trends. Metabolism 1972;21:197-204.
Inoue M, Taketani N, Sato T, Nakajima H. High incidence of chronic lymphocytic thyroiditis in apparently healthy school children: Epidemiological and clinical study. Endocrinol Jpn 1975;22:483-8.
Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab 1994;78:393-7.
Szabolcs I, Podoba J, Feldkamp J, Dohan O, Farkas I, Sajgó M, et al.
Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake. Clin Endocrinol (Oxf) 1997;47:87-92.
Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen PR. Iodine intake and the pattern of thyroid disorders: A comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. J Clin Endocrinol Metab 1998;83:765-9.
Nobuyuki A, Kiyoshi M, Toshio O, Takuma H, Kayoko A, Kaichiro I, et al
. Transient hypothyroidism after delivery in autoimmune thyroiditis. JCEM 1976;42:296-301.
Lervang HH, Pryds O, Ostergaard Kristensen HP. Thyroid dysfunction after delivery: Incidence and clinical course. Acta Med Scand 1987;222:369-74.
Carlé A, Laurberg P, Pedersen IB, Knudsen N, Perrild H, Ovesen L, et al.
Epidemiology of subtypes of hypothyroidism in Denmark. Eur J Endocrinol 2006;154:21-8.
Chhetri MK, De B, Nandi SM, Banerjee PK. Observations of hypothyroidism (based on 94 cases). JAPI 1968;16;709-19.
Goslings BM, Djokomeljanto R, Doctor R, Van Hardefeld C, Hennemann G, Smeenk D, et al
. Hypothyroidism in an area of endemic goitre and cretinism in Central Java, Indonesia. JCEM 1977;44:481-90.
Marwaha RK, Tandon N, Gupta N, Karak AK, Verma K, Kochupillai N. Residual goitre in the postiodization phase: Iodine status, thiocyanate exposure and autoimmunity. Clin Endocrinol (Oxf) 2003;59:672-81.
Honbo KS, van Herle AJ, Kellett KA. Serum prolactin levels in untreated primary hypothyroidism. Am J Med 1978;64:782-7.
Seshadri MS, Samuel BU, Kanagasabapathy AS, Cherian AM. Clinical scoring system for hypothyroidism: Is it useful? J Gen Intern Med 1989;4:490-2.
Kumkum A. Hyperprolactinema and its correlation with hypothyroidism in infertile women. J Obstet Gynecol India 2006;56:68-71.
Doufas AG, Mastorakos G. The hypothalamic-pituitary-thyroid axis and the female reproductive system. Ann N
Y Acad Sci 2000;900:65-76.
Martinez-Soto T, Deal C, Stephure D, Trussell R, Boutin C, Djemli A, et al.
Pericardial effusion in severe hypothyroidism in children. J Pediatr Endocrinol Metab 2010;23:1165-8.
Thirone AC, Danieli RV, Ribeiro VM. Massive pericardial effusion as initial manifestation of hypothyroidism. Arq Bras Endocrinol Metabol 2012;56:383-7.
Koo KS, Barnard R, Kagawa FT, Chen W, Hinojosa I. Chylous effusion presenting in a 37-year-old woman with severe hypothyroidism: A case report. J Med Case Rep 2010;4:336.
Martí V, Guarinos J, Domínguez de Rozas JM. Massive pericardial effusion and cardiac tamponade as the presentation form of hypothyroidism. Rev Med Chil 2001;129:1191-4.
Gottehrer A, Roa J, Stanford GG, Chernow B, Sahn SA. Hypothyroidism and pleural effusions. Chest 1990;98:1130-2.
Gall WW. On a cretinoid state supervening in adult life in women. Trans Clin Soc (Lond) 1873;7:180.
Report of a Committee of the Clinical Society of London. Report on Myxedema. Trans Clin Soc (Suppl) (Lond) 1888;21:18.
Asher R. Myxoedematous madness. Br Med J 1949;2:555-62.
Das KC, Mukherjee M, Sarkar TK, Dash RJ, Rastogi GK. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism. J Clin Endocrinol Metab 1975;40:211-20.
Nekrasova TA, Strongin LG, Ledentsova OV. Hematological disturbances in subclinical hypothyroidism and their dynamics during substitution therapy. Klin Med (Mosk) 2013;91:29-33.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]