INTRODUCTION:

The thyroid gland is one of the largest glands in human body which is endocrine in nature. There exist synchronization between the nervous system, the endocrine and the immune system which brings about the quick and precise response to all environmental stimuli [1]. Major role of the gland is to produce thyroid hormones, also control how quickly the body uses energy and makes proteins and controls how sensitive the body is to other hormones and proteins for signal transduction; biosynthesis of some secondary metabolites and those whose function were unknown were slowly expressed [2]. Thyroid disorders are one among the most common endocrine disorders worldwide. In India too there is significant burden of thyroid diseases. According to a projection made from various studies on thyroid diseases, it has been estimated that about 42 million people in India suffer from some or the other thyroid disorders. [3]

Thyroid diseases are different from other diseases in terms of ease of diagnosis, accessibility of treatment, and also relative visibility that even a small swelling of thyroid offers to the treating physician. Early diagnosis and treatment remain as the basis of management. The prevalence and pattern of thyroid disorders depends on sex, age, ethnic and geographical factors and most importantly on iodine intake. [4] A high intake of iodine is associated with lower prevalence of goiter and hypothyroidism. Whereas low intake is related to higher prevalence of hyperthyroidism. [5] Hypothyroidism is more common in older women and 10 times more common in women than men. [6] The prevalence of hyperthyroidism is also reported to be more common in women than men. [7] Many studies conducted all over India show the high prevalence of goiter [8-11]. The overall incidence of thyroid cancer is usually not influenced by iodine intake in population but distribution of types of differentiated thyroid carcinoma may be related to intake of iodine. [12] This review will focus on the epidemiology of four different thyroid disorders in India: 1.Hypothyroidism; 2.Hyperthyroidism; 3.Goiter and Iodine deficiency disorders; and thyroid cancer (in detail). Rather than going into depth about these disorders this article will discuss about the studies made across the country and also the implications these studies bring forth.

HYPOTHYROIDISM:

Among various varieties of hypothyroidism, congenital hypothyroidism (CH) is the most important and the commonest metabolic disorder in newborn. It requires early diagnosis which has to be followed by appropriate treatment so as to prevent the onset of brain damage. CH is the major cause for preventable mental retardation in infants. Usual causes of primary CH are commonly grouped together as thyroid dysgenesis which includes maldevelopment (aplasia, hypoplasia) and maldescent (ectopia); also dyshormonogenesis and thyroiditis. [13,14]

Studies from Mumbai suggest that CH is common in India, the disease seen in 1 out of 2640 neonates, in comparison with the worldwide average of 1 in 3800 subjects. [14] There is often a delay in the diagnosis of this disease in the country and the main reason behind this delay is the lack of awareness and also lack of facilities, screening program and tests for this illness. Hypothyroidism is also commonly observed in children. It is reported that from the study carried out in a clinic in Mumbai, out of 800 children with thyroid disease, 79% had hypothyroidism [14]. Among the adult population in India, the prevalence of hypothyroidism has been recently studied. In this population-based study performed in Cochin on 971 adult subjects, the prevalence of hypothyroidism was 3.9% [15]. The prevalence of subclinical hypothyroidism was also high, the value being 9.4%. In women, the prevalence was higher, at about 11.4%, when compared to men, in whom the prevalence was lesser at about 6.2%. This prevalence of subclinical hypothyroidism increased with age. Averages of about 53% of the subjects with this disease were positive for anti-TPO antibodies. This was a population-based study which used the strategy of cluster sampling. [15] The low degree of awareness about the thyroid diseases lead to severe manifestations resulting in reports of rare presentations like multicystic ovaries in girls with hypothyroidism [16, 17].

HYPERTHYROIDISM:

The prevalence of hyperthyroidism has been studied in several studies. In an epidemiological study carried out from Cochin, subclinical and overt hyperthyroidism were present in about 1.6% and 1.3% respectively of the subjects who took part in the survey [15]. In a hospital-based study conducted in Pondicherry among the women population, subclinical and overt hyperthyroidism were present in 1.6% and 1.2% of subjects [18]. More than 33% of the community who were diagnosed with hyperthyroidism has positive anti-TPO antibodies, and about 39% of these subjects have goiter. ]. Regular use of coconut and its products in meals is a factor associated with hyperthyroidism. Since coconut has stimulating effects on thyroid and thereby it may cause hyperthyroidism says Chaturvedi [19]. Overt hyperthyroidism induces a hyperdynamic cardiovascular state which is associated with increased heart rate, enhance left ventricular systolic and diastolic function and increase in prevalence of atrial fibrillation, whereas the opposite changes occur in overt hypothyroidism [20]. In hyperthyroidism, patients with toxic multinodular goiter and Graves’ disease have an option of surgical management for permanent remission. Considering the high cost and limited availability of radioactive iodine, thyroidectomies are common in India. A demonstrative study of 325 cases of hyperthyroidism managed by surgery showed that the predominant cause was Graves’ disease(185) followed by toxic MNG(105), and autonomously functioning thyroid nodules(AFTN)(35). The complications include temporary hypocalcemia(24%), permanent hypocalcemia(3%), and permanent vocal-cord palsy(1%). Cost effectiveness of thyroid surgery with low complication rates should encourage this modality of treatment in Indian population [21].

GOITER AND IODINE DEFICIENCY:

Recent population studies have shown that about 12% of adults have palpable goiter [15]. Autoimmune thyroid disorders are commoner when compared to iodine deficiency as a cause of goiter in areas that are now iodine sufficient. However given that iodine deficiency is a huge problem in India, its importance cannot be underestimated in the Indian context. Several eminent Indian researchers have worked to find the link between endemic goiter and iodine deficiency, and this has led to the publication of various reports [22-24]. Critical research has reported the prevalence of endemic goiter from Himalayan and sub-Himalayan regions [3]. Researches from New Delhi shown that this was linked to iodine deficiency and that this resulted in decompensated hypothyroidism in many cases [3]. This led to a landmark study which showed that iodine deficiency was associated with hypothyroidism in neonates, setting the scene for a salt iodization program conducted by Government of India [3]. Subsequent to this program, it was shown that in some regions of Uttar Pradesh, the prevalence of congenital hypothyroidism had come down from 100 in 1000 to 18 in 1000 [3]. Several landmark studies have been carried out in many regions to assess the iodine deficiency disorders in the country [22-24]. In the post iodization phase in order to examine the prevalence of goiter several studies were conducted [25]. About 14,762 children from all over India were studied for the following characteristics: goiter prevalence, urinary iodine and thiocyanate excretion, functional status of the thyroid, as well as serological and cytopathological markers for thyroid autoimmunity. About 23% of subjects had a goiter. The authors suggested that despite of iodization, the prevalence of goiter has not dramatically declined [25].

Iodine deficiency diseases (IDD) refer to all the clinical and subclinical effects of iodine deficiency and can be prevented by adequate intake of iodine [26]. The effects of iodine deficiency are related to the adaptations of the thyroid gland to reduced iodine intake in diet, and the neurological and developmental defects related to reduce thyroid hormone synthesis by the gland.

THYROID CANCER:

Thyroid cancer starts in the thyroid gland. Increasing cancer incidence is typically interpreted as an increase in the true occurrence of the disease but may also reflect changing pathological criteria or increased diagnostic examination. Changes in the diagnostic approach to thyroid nodules may have resulted in an increase in the apparent incidence of thyroid cancer [27]. Head and neck squamous cell carcinoma (HNSCC) is highly invasive, frequently metastasizing to cervical lymph nodes and corresponds with poor prognosis [28]. Metastasis is the final stage of cancer and is still associated with high mortality despite breakthroughs in recent years [29]. Collaborations between physicians and laboratory researchers working to identify key clinical issues and translating the biological insights into novel therapeutic approaches are crucial to significant progress in the field [30]. Thyroid cancer constitutes a heterogeneous group of malignancies which exceeds half a million cases annually, ranking it as the fifth most common cancer worldwide [31]. The distribution of primary tumor sites is: Oral cavity (49%), Pharynx (23%) and Larynx (28%). Patients with recurrent, metastatic disease have a poor prognosis, with a median survival of around 6-7 months in addition, patients failing first-line therapeutic options [32]. As papillary micro-carcinomas can represent up to 30 % of all papillary cancers seen in thyroid surgeon’s practice, they are an important group [33]. Follicular thyroid cancer of the thyroid gland accounts for between 4% and 39%of all malignant thyroid tumors. Follicular carcinoma is more common in women who are affected over a broad age range [34]. Cancer is basically a cell disease, characterized by a loss in the mechanisms which drive the proliferation and cellular differentiation [35]. Cells were cultured and the proliferation was assessed by cell counting using a haemocytometer after trypsin digestion [36].

The Indian Council of Medical Research established the National Cancer Registry Program, and the NCRP has collected the data of more than 3, 00,000 cancer patients between the periods 1984 and 1993 [37]. Among these patients, the NCRP noted 5614 cases of thyroid cancer, and this included 3617 females and 2007 males. The six centres considered under the study were at Mumbai, Delhi, Thiruvananthapuram, Dibrugarh, Chandigarh, and Chennai. Among them, Thiruvananthapuram had the highest relative frequency of thyroid cancers among all the cancer cases enrolled in the hospital, 1.99% among male and 5.71% among females. The nationwide relative frequency of thyroid cancer among all the cancer cases was 0.1%-0.2%. The age-adjusted incidence rates of thyroid cancer per 100,000 are about 1 for males and 1.8 for females as per the Mumbai Cancer Registry, which covered a population of 9.81 million subjects. The histological types of thyroid cancer were studied in Hospital Cancer Registry of 1185 “new cases” of thyroid cancer [38]. The commonest cancer type was papillary, followed by follicular type.

A study by Bal et al was based on the prevalence of thyroid malignancies in children.85% of 122 patients had papillary carcinoma of thyroid. The disease was found to be more aggressive and widespread in younger age groups (< or = 10 years), with male predominance and high mortality. Cervical lymph node involvement was seen in 66% of patients, and distant metastasis, mainly pulmonary, in 29%. In children less than 10 years of age, 75% of patients had distant metastasis at the time of presentation [39]. Although the distribution of malignancy according to the types is similar to world literature, the incidence of distant metastasis is significantly more than that reported from iodine sufficient areas of the world [40]. Whether these differences are due to iodine deficiency per se or is contributed by a referral bias and late presentation in India is not clear. Epidemiological studies of cancer in India show an increased incidence of thyroid cancers in females in southwest coastal districts and also in Kerala [41, 42]

Surgery is the most effective treatment for thyroid cancer; however, in some subsets of patients, the role of radiotherapy (RT) is important. The main indication for external-beam RT is incomplete surgery. When neoplastic tissue is left behind at operation, RT must be considered, but only if an experienced surgeon feels that everything that can be done has been done. Generally, in those patients, the neoplastic tissue involves the larynx, trachea, oesophagus, blood vessels or mediastinum [43]. Cancer chemotherapy aim is to minimize the tumor burden at the end of the treatment period while maintaining a normal cell population above a lower level as a limit of toxicity [44]. Tumor cell invasion and metastasis is a compounding problem in cancer management, with therapeutic intervention of tumor invasion becoming recognized as an increasingly relevant clinical factor [45].

CONCLUSION:

In summary, there is a high burden of thyroid diseases in India. There is a scarcity of data on the epidemiology of thyroid disease. Due to lack of resources, screening for thyroid diseases in the general population is not cost effective. However, ensuring adequate iodine nutrition of pregnant women and children and screening for congenital hypothyroidism are interventions that require a priority in the Indian population. Iodine nutrition should be ensured in all women of reproductive age group especially in areas identified to be endemic for iodine deficiency disease. Aggressive case finding in pregnant women at risk for thyroid disease should be done. Targeted screening for thyroid diseases in high risk population in all age groups can be carried out. In the view of low incidence of thyroid cancers, community screening for thyroid cancer is not warranted. Congenital hypothyroidism screening for all the new born and establishment of a national screening program can be done. Family screening for first degree relatives in all patients with juvenile autoimmune thyroiditis should be conducted. All the above suggestions are based on evidence from Indian and Western literature and clinical guidelines of various organizations. Implementing these measures would go a long way in improving the thyroid health of our population.

REFERENCES:

1 Dronca RS, Markovic SN, Holtan SG, Porrata LF (2011) Neuroendocrineimmune Crosstalk and Implications for Cancer Therapy. J Cell Sci Ther 2:102e.

2 Ying J, Quanjun W, Jinglan W, Songfeng W, Gang C, et al. (2008). Profiling of Phosphorylated Proteins in Human Fetal Liver. J Proteomics Bioinform 1:437-457.

3 Last accessed on 2011 April 2. Available from:http://www.ias.ac.in/currsci/oct252000/n%20kochupillai.PDF.

4 N. Kochupillai, “Clinical endocrinology in India” in Current Science. Vol 79, P. Balram, Ed. India: Current science Association, 2000, pp. 1061-7.

5 P. Laurberg, K. M. Pedersen, A. Hreidarsson, N. Sigfusson, E. Iversen and P. R. Knudsen, “Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark” in The Journal of Clinical Endocrinology and Metabolism. Vol 83, 1998, pp. 765-9

6 M. P. Vanderpump and W. M. Tunbridge, “Epidemiology and prevention of clinical and subclinical hypothyroidism” in Thyroid. Vol 12, H. E. Charles, Ed. USA, Mary Ann Liebert, Inc, 2002, pp. 839-47

7 W. M. Tunbridge and M. P. J. Vanderpump, “Population Screening for autoimmune thyroid disease” in Endocrinology and Metabolism Clinics of North America. Vol 29, Elsevier, 2000, pp. 239-53

8 Directorate General of Health Services (DGHS). Ministry of Health and Family Welfare, Govt. of India. Policy Guidelines on National Iodine Deficiency Disorders Control Programme. New Delhi; 2003; p. 1-10.

9 ICMR. Epidemiological survey of endemic goiter and endemic cretinism. New Delhi: Indian Council of Medical Research; 1989.

10 Indicators for Assessing Iodine Deficiency Disorders andtheir Control Programmes. Report of a Joint WHO/UNICEF/ICCIDD Consultation, Geneva: World HealthOrganization; 1992. p. 22-29.

11 Control of iodine deficiency through safe use of iodizedsalt. ICMR Bull. 1996; 26: 41-46.

12 Rasmussen-Ulla Feldt. Iodine and cancer. Thyroid 2001:11;483-486.

13 Mesai MP , The Thyroid Gland in Pediatric Endocrine Disorders Orient Longman Ed Desai MP, Bhatia V, Menon PSN. 1st Edition pp 183- 202

14 Desai PM. Disorders of the Thyroid Gland in India. Indian J Pediatr. 1997;64:11–20. PubMed

15 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. PubMed

16 Dhanwal D, Tandon N. Isolated menarche and multicystic ovaries in a 7 1/2 year girl with hypothyroidism. Indian Pediatr. 2001 Apr; 38(4): 432-3.

17 Bandgar T, Mappa P, John M, Multani SK, Shah NS, Menon PS Primary hypothyroidism: unusual presentations. Abstract in Annual Conference of Indian Thyroid society 2004, Cochin.

18 Abraham R, Murugan VS, Pukazhvanthen P, Sen SK. Thyroid Disorders In Women of Puducherry.Indian J Clin Biochem. 2009;24:52–9. PMC free article PubMed

19 Chaturvedi S , Sanjay M, Pushpa Gupta and et al Assesment of iodine induced Disorders. JIMA, 2006;94:127-35.

20 Jayakumar RV, Nisha B, Unnikrishnan AG, Nair V, Kumar H. Thyroidstatus in metabolic syndrome – a clinical study. Thyroid Researchand Practice,2010;366-370

21 Pradeep PV, Agarwal A, Baxi M, Agarwal G, Gupta SK,Mishra SK. Safety and efficacy of surgical management of hyperthyroidism: 15-year experience from a tertiary care center in a developing country. World J Surg. 2007 Feb; 31(2):306-12

22 Karmarkar MG, Deo MG, Kochupillai N, Ramalingaswami V. Pathophysiology of Himalayan endemic goiter. Am J Clin Nutr. 1974;27:96–103. PubMed

23 Sooch SS, Deo MG, Karmarkar MG, Kochupillai N, Ramachandran K, Ramalingaswami V. Prevention of endemic goitre with iodized salt. 1973. Natl Med J India. 2001;14:185–8. PubMed

24 Pandav CS, Karmarkar MG, Kochupillai N. Recommended levels of salt iodation in India. Indian J Pediatr. 1984;51:53–4. PubMed

25 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. PubMed

26 Hetzel BS.Iodine Deficiency Disorders (IDD) and their eradication. Lancet 1983; 2: 1126-1129.

27 Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States. JAMA 295: 2164-2167.

28 Ammer AG, Kelley LC, Hayes KE, Evans JV, Lopez-Skinner LA, et al. (2009) Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function. J Cancer Sci Ther 1: 052-061.

29 Pierre M, DeHertogh B, DeMeulder B, Bareke E, Depiereux S, et al. (2011) Enhanced Meta-analysis Highlights Genes Involved in Metastasis from Several Microarray Datasets. J Proteomics Bioinform 4: 036-043.

30 Thomas SM (2011) Otolaryngology Research: A New frontier in Head and Neck Cancer Genomics. Otolaryngology 1:102e.

31 Hamed RH, Elzahaf E (2011) Low Dose Weekly Paclitaxel Versus Low Dose Weekly Cisplatin with Concomitant Radiation in Locally Advanced Head andNeck Cancers. J Cancer Sci Ther 3: 166-171.

32 Mesía R, Vilajosana E, Lozano A, Esteller L, Silvia V (2009) Management of Cutaneous Toxicity and Radiation Dermatitis in Patients with Squamous Cancer of the Head and Neck Undergoing Concurrent Treatment with Cetuximab and Radiotherapy. J Cancer Sci Ther 1: 028- 033.

33 Bramley MD, Harrison BJ (1996) papillary microcarcinoma of the thyroid gland. Br J Surg 83: 1674-1683.

34 Thompson LD, Wieneke JA, Paal E, Frommelt RA, Adair CF (2001) A clinic pathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature. Cancer 91: 505-524.

35 Ferreira AK, Meneguelo R, Neto SC, Chierice GO, Maria DA (2011) SyntheticPhosphoethanolamine Induces Apoptosis Through Caspase-3 Pathway by Decreasing Expression of Bax/Bad Protein and Changes Cell Cycle in Melanoma. J Cancer Sci Ther 3: 053-059.

36 Zhu W, Masaki T , Cheung AK, Kern SE (2009) In-vitro Release of Rapamycin from a Thermosensitive Polymer for the Inhibition of Vascular Smooth Muscle Cell Proliferation. J Bioequiv Availab 1: 003-012.

37 Rao DN. Thyroid Cancer- An Indian Perspective. In: Shah AH, Samuel AM, Rao RS, editors.Thyroid Cancer- An Indian Perspective. Mumbai: Quest Publications; 1999. pp. 3–16.

38 Gangadharan P, Nair MK, Pradeep VM. Thyroid Cancer in Kerala. In: Shah AH, Samuel AM, Rao RS, editors. Thyroid Cancer- An Indian Perspective. Mumbai: Quest Publications; 1999. pp. 17–32.

39 Bal CS, Kumar A Differentiated thyroid cancer Indian JPediatr. 2003 Sep; 70(9): 707-13

40 Wiersinga WM, Differentiated Thyroid Carcinoma in Pediatric Age In Krassas GE, Rivkees SA, Kiess W (eds):Diseases of the Thyroid in Childhood and Adolescence.Pediatr Adolesc Med. Basel, Karger, 2007, vol 11, pp 210–224.

41 Nandakumar A, Gupta PC, Gangadharan P, Visweswara RN,Parkin DM. Geographic pathology revisited: development of an atlas of cancer in India. Int J Cancer. 2005 Sep 20; 116(5):740-54.

42 Jayalekshmi P, Gangadharan P, Mani KS Cancer in women in Kerala--a transition from a less-developed state. Asian Pac J Cancer Prev. 2006 Apr-Jun; 7(2): 186-90

43 Tubiana M, Haddad E, Schlumberger M, Hill C, Rougier P (1985) External radiotherapy in thyroid cancers. Cancer 55: 2062-2071.

44 Murray JM (1990) Optimal control for a cancer chemotherapy problem with general growth and loss functions. Math Biosci 98: 273-287.

45 Ammer AG, Kelley LC, Hayes KE, Evans JV, Lopez-Skinner LA, et al. (2009) Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function. J Cancer Sci Ther 1: 052-061.

Received on 04.03.2014 Modified on 05.06.2014

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