|Year : 2018 | Volume
| Issue : 3 | Page : 113-116
Postprandial decline in thyroid-stimulating hormone is significant but not its correlation with postprandial change in plasma glucose
T V S Pradeep, Sree Harsha Varma, Sunanda Tirupati, Vijaya Sarathi, K Dileep Kumar
Department of Endocrinology, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India
|Date of Web Publication||15-Nov-2018|
Dr. Sunanda Tirupati
Department of Endocrinology, Narayana Medical College and Hospital, Nellore - 524 003, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: There are limited data on postprandial change in serum thyroid-stimulating hormone (TSH), especially on its correlation with postprandial change in plasma glucose. Hence, we evaluated the postprandial changes in thyroid function tests (TFTs) and their correlation with postprandial changes in plasma glucose.
Materials and Methods: This prospective, cross-sectional study was conducted at a tertiary care hospital from South India. The study included 200 participants: 75 healthy volunteers without known thyroid dysfunction (Group A), 65 healthy pregnant women (Group B), and 60 patients who were known hypothyroid (clinical and subclinical hypothyroid) on levothyroxine therapy (Group C). All participants underwent biochemical investigations including plasma glucose and TFTs in fasting and 2-h postprandial states.
Results: Serum TSH was significantly lower in the postprandial state than fasting sample in all the three groups, whereas the free triiodothyronine and free thyroxine levels were not significantly different in fasting and postprandial states. There was no significant correlation between change in plasma glucose and the change in TFT in any group. In pregnant women (Group B), the prevalence of hypothyroidism was significantly higher in fasting than postprandial while using a cutoff of 2.5 μIU/ml (41.5% vs. 18.4%, P = 0.004) as well as 4 μIU/ml (12.3% vs. 1.5%, P = 0.03) but not in other groups (Group A and Group C).
Conclusion: Our study reports significant TSH decline in the postprandial state but no significant correlation between postprandial changes in plasma glucose and TSH.
Keywords: Correlation with glucose, fasting, postprandial, thyroid function tests
|How to cite this article:|
Pradeep T V, Varma SH, Tirupati S, Sarathi V, Kumar K D. Postprandial decline in thyroid-stimulating hormone is significant but not its correlation with postprandial change in plasma glucose. Thyroid Res Pract 2018;15:113-6
|How to cite this URL:|
Pradeep T V, Varma SH, Tirupati S, Sarathi V, Kumar K D. Postprandial decline in thyroid-stimulating hormone is significant but not its correlation with postprandial change in plasma glucose. Thyroid Res Pract [serial online] 2018 [cited 2022 May 17];15:113-6. Available from: https://www.thetrp.net/text.asp?2018/15/3/113/245565
| Introduction|| |
Primary hypothyroidism is one of the most common endocrine disorders affecting many millions around the world. Subclinical hypothyroidism (SCH, 4.3%) is more common than overt hypothyroidism (0.3%). Although SCH is a milder form of hypothyroidism, it is associated with several long-term effects such as dyslipidemia, hypertension, and subfertility and may be an independent risk factor for cardiovascular morbidity. SCH in pregnancy has greater effect on maternal health as it is associated with increased risk of gestational hypertension, anemia, abruptio placentae, and postpartum hemorrhage as well as on fetal health due to its association with miscarriages, preterm delivery, stillbirth, and decreased IQ in children. Hence, appropriate diagnosis of SCH is essential, and accurate estimation of thyroid-stimulating hormone (TSH) is critical in the diagnosis of SCH.
Few studies have demonstrated postprandial decline in TSH.,, Underestimation of the prevalence of SCH using postprandial TSH has been demonstrated in general population as well as in pregnant women. However, the data are limited. In addition, the effect of using postprandial TSH in the optimization of levothyroxine replacement in patients with hypothyroidism is not studied.
Diurnal variations and fed status have been claimed to alter TSH levels, and diurnal variation in TSH is a main confounding factor in the assessment of effect of postprandial state on changes in TSH.,, Hence, the exact cause for postprandial TSH decline remains obscured. Postprandial somatostatin release has been proposed as the cause of postprandial TSH decline. Postprandial rise in plasma glucose is the most likely cause for postprandial somatostatin release, but the data on correlation of postprandial TSH change with postprandial change in plasma glucose are limited. Evaluation of correlation between the two may enhance pathophysiological understanding of postprandial TSH decline. Hence, this study was conducted to verify the postprandial alteration in thyroid function tests (TFTs) in different groups of population and to find correlation of change in plasma glucose levels with those in TFT.
| Materials and Methods|| |
This is a cross-sectional study conducted in the Department of Endocrinology, Narayana Medical College and Hospital, Nellore, during the period from September 2016 to September 2017. In this study, 200 participants comprising into 3 groups were included after obtaining a written informed consent. The study was approved by the Institutional Ethics Committee.
- Group A: 75 healthy volunteers without known thyroid dysfunction
- Group B: 65 healthy pregnant women (including all trimesters)
- Group C: 60 patients who are known hypothyroid (clinical and subclinical hypothyroid) on levothyroxine therapy were included in the study.
Participants who were hyperthyroid and had history suspected thyroiditis, radioiodine treatment, recent hospitalization for critical illness, and use of drugs interfering with thyroid function such as amiodarone, iodine-containing drugs, and glucocorticoids, within last 6 months, were excluded from the study. History of diabetes mellitus and hypertension and family history of thyroid dysfunction were obtained from all patients. Examination included measurement of blood pressure and thyroid examination.
Venous blood samples for fasting and postprandial plasma glucose, fasting lipid profile, fasting, and postprandial thyroid profile (free triiodothyronine [FT3], free thyroxine [FT4], and TSH) were collected after an overnight fast. Biochemical investigations were performed using HumaStar 600, whereas hormonal investigations were performed using Beckman Coulter Access 2. For all the above parameters, any value more than the upper limit of the laboratory reference range was used as abnormal. For serum TSH assay, analytical sensitivity, reference range, and precision were 0.003, 0.34–5.60, and 0.015 μIU/ml, respectively, with intra-assay coefficient of variation (CV) of 6.5%, whereas for serum FT3 and FT4 assay, analytical sensitivity is 0.25 ng/ml and 0.88 pg/ml, respectively, reference range is 0.61–1.12 ng/dl and 2.5–3.9 pg/ml, respectively, and precision value is 0.9 ng/dl and 2.0 pg/ml, respectively, with intra-assay CV of 5.3% and 5.7%, respectively.
All the data were entered into MS Excel worksheet. Statistical analysis was done by using SPSS version 21.0, IBM, Armonk, NY. Categorical variables were represented as frequencies and percentages. For continuous variables, the data values were shown as mean and standard deviation. Paired sample t-test was used to compare the variables in fasting and postprandial states. One-way ANOVA was used compare the differences between the three groups. To test correlation between the variables, Pearson's correlation coefficient was used. P < 0.05 was considered as statistically significant.
| Results|| |
The study included a total of 200 participants. The mean age of the study population was 44 ± 15, 24 ± 4.5, and 43 ± 13 years in Groups A, B, and C, respectively. Diabetes mellitus, hypertension, and family history of thyroid dysfunction were present in 34 (55%), 12 (16%), and 7 (9.3%) in Group A, 4 (6.2%), 4 (6.2%), and 13 (20%) in Group B, and 16 (27%), 13 (22%), and 24 (40%) in Group C, respectively. Goiter was observed in 9 (12%), 21 (32%), and 29 (47%) participants in Groups A, B, and C, respectively.
TSH was significantly higher in the fasting state than in postprandial state in all the three groups. FT3 and FT4 were not different in the fasting and postprandial states in any of the groups [Table 1]. Postprandial plasma glucose was significantly higher than fasting plasma glucose. Although the absolute change in TSH was significantly more in the hypothyroid group, percentage change in TSH was significantly more in the pregnant women than healthy volunteers.
|Table 1: Thyroid function tests and plasma glucose in fasting and postprandial state|
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There was no significant correlation between change in plasma glucose and change in TFT in any of the three groups [Table 2].
|Table 2: Correlation of change in plasma glucose with change in thyroid function tests|
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Using the hospital-based TSH reference ranges (cutoff: 5.6 μIU/ml) for fasting and postprandial values, the prevalence of hypothyroidism was not significantly different (9.3% vs. 6.7%, P = 0.54) in healthy volunteers (Group A). In pregnant women (Group B), the prevalence of hypothyroidism was significantly higher in fasting than postprandial while using a cutoff of 2.5 μIU/ml (41.5% vs. 18.4%, P = 0.004) as well as 4 μIU/ml (12.3% vs. 1.5%, P = 0.03). Among known hypothyroidism patients (Group C), the prevalence of patients with supranormal TSH was not significantly different using fasting and postprandial TSH (33.3% vs. 23.3%, P = 0.22).
| Discussion|| |
In our study, we observed that FT3 and FT4 would not alter significantly, whereas TSH values were lower in postprandial state than those in fasting state. None of the previous studies which studied postprandial changes in TFTs have reported significant changes in the postprandial FT3 and FT4, whereas most of the previous studies have reported postprandial TSH decline.,, Although the TSH declined significantly in all the three groups, percentage postprandial decline in TSH was significantly more in the pregnant women than healthy volunteers; however, the reason for this observation is not known.
Secretion of TSH is mainly regulated by TSH-releasing hormone and somatostatin; the former stimulating and the latter inhibiting TSH secretion. Elevation of circulating somatostatin associated with food intake has been proposed to be responsible for postprandial TSH suppression. Rise in plasma glucose is the most likely factor causing postprandial elevation of somatostatin. However, in our study, there was no significant correlation between them. Hence, postprandial change in factors other than plasma glucose such as cytokines or interleukins which may act either directly or by increasing somatostatin release might have caused postprandial TSH decline., Otherwise postprandial TSH may be due to physiological diurnal variation.
Circulating TSH shows a normal circadian rhythm with a peak between 2300 and 0500 and a nadir between 0900 and 1200 h. Secretory pulses occur every 90 min and are interspersed with periods of tonic nonpulsatile TSH secretion. Although the TSH secretion is pulsatile, the low amplitude of the pulses and the long half-life of TSH results in only a modest variation in serum TSH levels. However, it is generally observed that TSH in early morning fasting states was higher than TSH levels measured later in the same day. Changes in TSH level due to this diurnal rhythm may be the physiological reason for the postprandial TSH fall seen in our study. Few studies report comparable TSH fall in postprandial and extended fasting states suggesting that postprandial TSH fall is related to circadian rhythm rather than fed status.,,, Hence, the time of sampling may be more important than the fed status for accurate estimation of TSH.
In routine clinical practice, much importance is not given to the timing of the sample or the fasting/nonfasting status of the patient. However, an entity like SCH which heavily relies on TSH values may be under- or over-diagnosed based on a single value. The use of postprandial sample underestimated the prevalence of SCH in all groups of our study but was significant only in pregnant women. More pronounced effect in pregnant women may be due to overlapping of TSH cutoff to define hypothyroidism in pregnancy with normal reference ranges for nonpregnant adults. Pregnant women are the special population where accurate measurement of TSH is most important since the approach to elevated TSH during pregnancy varies significantly over a narrow margin; no intervention for TSH <2.5 μIU/ml, testing thyroid antibodies for TSH between 2.5 and 4 μIU/ml and initiating levothyroxine for TSH more than 4 μIU/ml. Hence, for the diagnosis of SCH in pregnancy, sampling for TSH should be done in the early morning which typically happens in the fasting state.
Although insignificant, lesser number of healthy volunteers were diagnosed as hypothyroidism and lesser number of hypothyroidism patients on levothyroxine met the criteria for increase in replacement dose using postprandial TSH than using fasting TSH. It suggests that the use of postprandial TSH may lead to underdiagnosis of hypothyroidism in few healthy volunteers and under replacement of levothyroxine in few hypothyroid patients. Hence, diagnosis of SCH in healthy volunteers and optimum replacement of levothyroxine in hypothyroidism patients may also require TSH measurement in the early morning, fasting sample.
Assuming an alpha error of 0.05, the study had a statistical power of 80% to rule out a correlation of 0.2 or more between postprandial change in plasma glucose and TSH. Hence, larger studies may be required to rule out a minor correlation between the two. Effect of extended fasting on TSH helps to adjust for the diurnal variation; however, it was not evaluated in our study.
| Conclusion|| |
Our study reports significant postprandial TSH decline in all the three groups with significant underestimation of hypothyroidism using postprandial TSH level in pregnancy. Hence, sampling for TSH, especially in pregnant women, should be done in the early morning which typically happens in the fasting state. Postprandial change in plasma glucose did not correlate with that in TSH suggesting other possible mechanisms for postprandial TSH decline.
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[Table 1], [Table 2]