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Table of Contents
Year : 2016  |  Volume : 20  |  Issue : 6  |  Page : 744-745

The rule of two-thirds in thyroid epidemiology

1 Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India
2 CEO, Chellaram Diabetes Institute, Pune, Maharashtra, India
3 Department of Endocrinology, Golden Hospital, Jalandhar City, Punjab, India

Date of Web Publication24-Oct-2016

Correspondence Address:
Sanjay Kalra
Department of Endocrinology, Bharti Hospital, Karnal, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2230-8210.192919

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How to cite this article:
Kalra S, Unnikrishnan A G, Talwar V. The rule of two-thirds in thyroid epidemiology. Indian J Endocr Metab 2016;20:744-5

How to cite this URL:
Kalra S, Unnikrishnan A G, Talwar V. The rule of two-thirds in thyroid epidemiology. Indian J Endocr Metab [serial online] 2016 [cited 2021 Sep 21];20:744-5. Available from: https://www.ijem.in/text.asp?2016/20/6/744/192919

   Rule of Halves Top

The rule of halves is accepted as a reality in chronic disease epidemiology, including diabetes, hypertension, and depression.[1],[2],[3] Broadly speaking, the rule states that only one-half of persons living with a particular chronic condition are diagnosed or known to have it; one-half of those who are diagnosed seek treatment, and one-half of those who seek treatment achieve desired therapeutic goals.

An extension of the rule of halves can also be made. We propose that “if properly defined, half of all persons with a predisease state convert to clinical disease For example, 50% of persons with prediabetes, progress to diabetes.[4]

   Indian Thyroid Epidemiology Top

In this editorial, we assess Indian epidemiological studies on thyroid disorders through the “rule of halves” mirror. There are three large-scale epidemiological studies on thyroid disorders which have been published from India.[5],[6],[7] These landmark efforts have served to highlight the heavy burden of thyroid dysfunction and disease in the country. Results from the two studies which assessed adult populations have shown a high prevalence of thyroid autoimmunity and subclinical hypothyroidism (SCH).[5],[6] Overt hypothyroidism (OH) is less frequent, through the eight-city study may have over-reported its prevalence due to bias resulting from following a camp-based strategy to recruit participants.[5]

   Known Diagnosis Top

Unnikrishnan et al. enrolled 5376 participants across eight cities in India and reported overall OH prevalence of 10.95% (n = 587). Of these 587 participants, 186 had previously undetected hypothyroidism while 401 were self-reported cases. Thus, one-third (31.7%) of all hypothyroid subjects did not know they had the condition. An equally accurate statement would be that two-thirds of all hypothyroid persons are aware of their diagnosis.

   Optimal Therapeutic Outcome Top

Of the 401 self-reported cases, accurate dosing details of thyroxine therapy were available with 379 patients. Relative to diabetes and depression, thyroid disorders are relatively easy to treat. Keeping this in mind, the rule of halves is not expected to apply to treatment outcomes in thyroidology. Rather, a law of two-thirds could operate. The mean thyroid-stimulating hormone (TSH) values reported by Unnikrishnan et al. suggest the same. Among these 379 participants, 272 had a TSH <5.5 μIU/mL, while the remaining one-third (n = 107, 28.23%) had a TSH >5.5 μIU/mL, in spite of being on a similar dose of thyroxine.

As a hypothesis, it could be proposed that another rule of two-thirds is operational in clinical thyroidology practice. The law states “of all persons who receive appropriate medical therapy for thyroid disorders, only two-thirds adhere to, or persist with treatment as advised by the physician. However, this law needs to be corroborated by further research.

   Conversion from Subclinical to Clinical Hypothyroidism Top

SCH was observed in 430 (8.02%) participants in the eight-city study. The SCH: OH ratio thus becomes 430:587 or 0.73, which is quite close to two-thirds. However, when the same ratio is assessed for SCH and newly diagnosed OH (excluding persons with a known history of hypothyroidism), it becomes 186: 430 or 0.43, which is slightly more than one-third.

   Conversion from Antibody Positivity to Hypothyroidism Top

A total of 1171 subjects tested positive for anti-thyroid peroxidase antibody. Antibody positivity is known to be a predisease state. The prevalence of (OH + SCH) as compared to all antibody-positive persons was (587 + 430): 1171 or 1017:1171 or nearly one. When we assess all SCH as a function of all antibody-positive participants, however, the ratio turns out to be 430:1171 or 0.37. Thus, the ratio of the number of antibody positive persons to individuals with SCH is approximately 2:1.

   Hyperthyroidism Top

A total of 36 (0.67%) participants were diagnosed with hyperthyroidism, while subclinical hyperthyroidism was seen in 68 (1.27%) subjects. Here, too a rule of two-thirds seems to be in operation: subclinical hyperthyroidism contributes to two-thirds (65.8%) of the total number of all hyperthyroid disorders.

   Summary Top

We, therefore, propose that a rule of thirds, rather than the rule of halves, operates in the Indian thyroid epidemiology. One-third of all antibody-positive persons convert to SCH; two-thirds of those convert to OH (one-third if only newly diagnosed OH is assessed); two-thirds of all OH are diagnosed, and two-thirds of all OH who receive thyroxine are well controlled.

The general health camp-based methodology of Unnikrishnan et al., with its inherent selection bias, is a limitation which must be noted while making such claims. The results of this study are therefore not to be used to make epidemiological presumptions in the Indian setting. At the same time, it is possible that large-scale availability of direct access testing for thyroid function [8]), and concerted efforts in social marketing of timely thyroid care [9] have led to a greater prevalence of known thyroid dysfunction, rather than the unknown disease. Larger epidemiological research with robust study design, therefore, is required to confirm this rule.

   References Top

Smith WC, Lee AJ, Crombie IK, Tunstall-Pedoe H. Control of blood pressure in Scotland: The rule of halves. BMJ 1990;300:981-3.  Back to cited text no. 1
Deepa R, Shanthirani CS, Pradeepa R, Mohan V. Is the 'rule of halves' in hypertension still valid? – Evidence from the Chennai urban population study. J Assoc Physicians India 2003;51:153-7.  Back to cited text no. 2
Pence BW, O'Donnell JK, Gaynes BN. The depression treatment cascade in primary care: A public health perspective. Curr Psychiatry Rep 2012;14:328-35.  Back to cited text no. 3
Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: A high-risk state for diabetes development. Lancet 2012;379:2279-90.  Back to cited text no. 4
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.  Back to cited text no. 5
Marwaha RK, Tandon N, Ganie MA, Kanwar R, Singh S, Garg MK, et al. Status of thyroid function in Indian adults: Two decades after universal salt iodization. J Assoc Physicians India 2012;60:32-6.  Back to cited text no. 6
Desai MP. Disorders of thyroid gland in India. Indian J Pediatr 1997;64:11-20.  Back to cited text no. 7
Kalra S, Kalra B, Sawhney K. Direct access testing in thyroidology: Perils aplenty. Thyroid Res Pract 2013;10:35.  Back to cited text no. 8
  Medknow Journal  
Kalra S, Unnikrishnan AG, Sahay R. Thyroidology and public health: The challenges ahead. Indian J Endocrinol Metab 2011;15 Suppl 2:S73-5.  Back to cited text no. 9


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