Impact of Laparoscopic Sleeve Gastrectomy on Obese Patients with Subclinical Hypothyroidism

Abstract

Background:

This study aims to evaluate the incidence of subclinical hypothyroidism (SCH) among studied obese patients. The effects of laparoscopic sleeve gastrectomy (LSG) and loss of weight on thyroid hormones level and the impact of adding thyroxine treatment is described.

Patients and Methods:

Obese patients undergoing LSG at the university hospital between June 2016 and January 2018 were included. Weight loss and changes in body mass index (BMI), serum thyroid stimulating hormone (TSH), and FT4 were evaluated. SCH patients were randomly divided into group “A” received thyroxine treatment and group “B” received no treatment.

Results:

There were 554 patients studied (mean age 41 ± 12 years); the mean preoperative BMI, serum TSH, and FT4 were 45 ± 6.8 kg/m², 3.91 ± 1 μU/mL, and 1.32 ± 1 ng, respectively. Incidence of SCH was 12.9%. Significant post-LSG decrease in BMI (30.8 ± 4.6 kg/m²) was associated with significant decrease in serum TSH (1.99 ± 1.1 μU/mL) in all patients; changes were more prominent in SCH group and in patients with higher BMI. SCH patients had normalization of mean serum TSH at 12 months post-LSG. Results of groups “A” and “B” were not significantly different.

Conclusion:

The incidence of SCH was 12.9%. The significant decrease in BMI was associated with a significant decrease in serum TSH after LSG; this was more evident in SCH and in patients with higher BMI. Complete resolution of SCH occurred at 12 months post-LSG. Adding thyroxine treatment in obese SCH patients did not improve outcome and should be reserved to specific clinical and laboratory indications.

Introduction

The metabolic disturbance in morbid obesity is reflected on many of the body physiological systems. Although the role of thyroid hormones in regulating body metabolism is well known, yet the relations between thyroid hormones and obesity is not well understood and have been the subject of many publications during the past two decades.^1,2

A positive correlation between thyroid stimulating hormone (TSH) level and body mass index (BMI) is reported in several studies^2,3; in these studies, high BMI levels were associated with increased TSH within the normal range but with no change in Free T4.

According to the American Thyroid Association, subclinical hypothyroidism (SCH) is diagnosed when serum TSH is greater than the normal range and serum FT4 is within the normal range.^4,5 This is contrary to clinical hypothyroidism where the TSH is increased above the normal range and FT4 is below the normal range. The incidence of SCH in general population varies between 4% and 9% and is associated with many cardiovascular comorbidities.⁶ In obese patients the incidence of SCH is higher.⁴ Recent data suggest that SCH may be secondary to obesity and not a true hypothyroidism hence the debatable question: To add hormonal treatment or not?

In this study we aim to evaluate the incidence of SCH in obese patients who underwent laparoscopic sleeve gastrectomy (LSG) during the study period and the impact of LSG and postoperative weight loss on serum thyroid hormone levels in these patients. The effect of adding hormone treatment in SCH patients on the outcome is evaluated.

Patients and Methods

After institutional review board approval, this study was conducted at the university main hospital between June 2016 and January 2018. All obese patients candidate for LSG according to international federation for surgery of obesity (IFSO) guidelines were included. Patients with history of thyroid disease or taking thyroid hormones, birth control pills, or any medications that might alter thyroid hormones levels were excluded.

Patients' baseline demographics and BMI were measured. Preoperative laboratory assessment included all the routine laboratory tests performed for Bariatric surgery including serum TSH and FT4; thyroid hormones were measured using the electro-chemi-luminescence Immunoassay method.⁵ In our laboratories the normal range for TSH and FT4 are 0.27–4.2 μU/mL and 0.93–1.71 ng/dL, respectively. SCH patients were randomly divided into two groups: group “A” received oral levothyroxine treatment 25–75 μg (weight adjusted dose 1.5 μ/kg) and group “B” received no treatment. At 6, 12, and 18 months post-LSG serum TSH, FT4 levels, and BMI, % excess weight loss (%EWL) were reassessed for all patients. Moreover, we divided the study cohort according to their BMI: <40 kg/m², 40–50 kg/m², and >50 kg/m²; the mean serum TSH and free T4 changes in the three BMI groups were evaluated at 12 months post-LSG.

Statistical analysis

Descriptive data are presented as mean (standard deviation) for continuous normally distributed variables, and frequency with proportions for nominal variables as appropriate. Continuous variables were compared using independent-sample t test for parametric variables. Categorical variables were compared using χ² test. A two-tailed level of significance of 0.05 was used for all analyses. All analyses were performed with SPSS version 17.0.

Results

During the study period 587 morbidly obese patients had LSG. Thirty-three patients (5.62%) were excluded as they had one or more of the exclusion criteria. The demographic characteristics of the remaining 554 patients showed that there were 430 women (77.61%) and 124 men (22.38%). The mean age was 41 ± 12 years (range 28–64 years) and the mean BMI was 45 ± 6.8 kg/m² (range 37–68 kg/m²). The mean serum TSH and FT4 were 3.91 ± 1 μU/mL and 1.32 ± 1 ng/dL, respectively.

Preoperative thyroid hormone assay revealed 72 patients (12.9%) with SCH and 482 (87%) euthyroid patients. In the SCH group there were 63 (87.5%) women, the mean age was 40.9 ± 4 years (range 29–65), and the mean BMI was 44.3 ± 4.1 kg/m². After LSG 35 of the SCH patients (gp A) were randomly chosen and given thyroid hormone (as mentioned earlier) and the remaining 37 patients (gp B) received no treatment. The pre- and postoperative mean serum TSH (μU/mL) and free T4 (ng/dL) levels for all studied patients are illustrated in Table 1. The follow-up rate varied between 80.55% and 91.6% during the postoperative visits.

Table 1.

Mean Serum Thyroid Stimulating Hormone and FT4 Levels Before and After Laparoscopic Sleeve Gastrectomy

	All patients (n = 554)	Euthyroid patients (n = 482)	All SCH patients (n = 72)	SCH group A (n = 35)	SCH group B (n = 37)	Group A/B (P)
TSH
Preoperative	3.91 ± 1	3.70 ± 0.9	5.31 ± 0.61	5.29 ± 0.71	5.35 ± 0.58	>.05
6 months	2.5 ± 0.9	2.3 ± 1.2	3.91 ± 0.8	3.88 ± 0.62	3.92 ± 0.71	>.05
6 months	P = .04	P = .04	P = .02	P = .02	P = .02	>.05
12 months	1.99 ± 1.1	1.92 ± 0.98	2.10 ± 0.8	2.09 ± 0.7	2.19 ± 0.61	>.05
12 months	P = .03	P = .03	P = .01	P = .01	P = .01	>.05
18 months	1.98 ± 1.1	1.95 ± 1	2.09 ± 0.79	2.09 ± 0.6	2.10 ± 0.62	>.05
18 months	P = .03	P = .03	P = .01	P = .01	P = .01	>.05
FT4
Preoperative	1.32 ± 1	1.31 ± 0.9	1.30 ± 0.17	1.31 ± 0.17	1.28 ± 0.17	>.05
6 months	1.26 ± 1.1	1.25 ± 0.98	1.18 ± 0.4	1.19 ± 0.11	1.19 ± 0.2	>.05
6 months	P = .4	P = .4	P = .03	P = .03	P = .03	>.05
12 months	1.24 ± 0.99	1.22 ± 0.98	1.19 ± 0.39	1.21 ± 0.19	1.18 ± 0.18	>.05
12 months	P = .2	P = .2	P = .03	P = .04	P = .04	>.05
18 months	1.24 ± 1.1	1.22 ± 0.99	1.19 ± 1.1	1.22 ± 0.2	1.20 ± 0.19	>.05
18 months	P = .2	P = .2	P = .03	P = .04	P = .04	>.05

Group A, received hormone treatment; Group B, received no treatment; Group A/B, significance between groups A and B (significant = P < .05).

Bold values indicate statistical significance.

n, number; SCH, subclinical hypothyroidism; TSH, thyroid stimulating hormone.

After LSG there was a gradual and significant decrease in serum TSH in all the study cohort. At 6 months post-LSG, resolution of SCH occurred in 63 (95.45%) of the 66 patients who attended for follow-up, mean TSH and FT4 were within the normal range. In 3 patients, however (1 in group “A” and 2 in group “B”), serum TSH decreased but was still above normal; these patients had a high preoperative TSH (between 6.1 and 7.1 ± 3.7 kg/m²). At 12 months a significant decrease in serum TSH occurred in all patients, and this decrease was more evident in SCH patients (from 5.31 ± 0.61 to 2.10 ± 0.8 μU/mL, P = .01); this was maintained during the 18 month follow-up visit as given in Table 1. The mean serum FT4 showed a significant decrease only in the SCH patients from 1.30 ± 0.17 to 1.19 ± 0.39 ng/dL (P = .03). There was no significant difference in the postoperative mean serum TSH and FT4 in the SCH patients between those who received hormone treatment and those who did not receive as shown in Table 1.

BMI decreased significantly after LSG in all the patients studied. The significant postoperative decrease in BMI was associated with a significant decrease in the mean serum TSH in all groups of patients: at 12 months in all the study cohort the mean BMI change from 45 ± 6.8 to 30.8 ± 4.6 was associated with decrease in TSH from 3.91 ± 1 to 1.99 ± 1.1 (P = .03); this relation was not, however, present with FT4 (Table 2). The decrease in mean serum TSH was more significant in patients with higher BMI (Table 3). The mean serum FT4 significantly decreased in SCH patients from 1.30 ± 0.17 to 1.19 ± 0.39 (P = .04), whereas in the euthyroid patients the decrease from 1.31 ± 0.9 to 1.22 ± 0.98 was nonsignificant (P = .2). No significant relation between the decrease in BMI and FT4 was found.

Table 2.

Relation Between Mean Body Mass Index, % Excess Weight Loss, Serum Thyroid Stimulating Hormone and FT4 Levels Before and 12 Months After Laparoscopic Sleeve Gastrectomy

	SCH Patients				Euthyroid patients		All patients
	Preoperative n = 72	12 months n = 62	Group A	Group B	Preoperative n = 482	12 months n = 422	Preoperative n = 554	12 months n = 484
BMI kg/m²	44.3 ± 4.1	30.9 ± 4.6	29.6 ± 8.1	31.1 ± 7	46.3 ± 48	31.3 ± 5.1	45 ± 6.8	30.8 ± 4.6
BMI kg/m²	44.3 ± 4.1	P = .01				P = .02		P = .02
TSH μU/mL	5.31 ± 2.5	2.10 ± 0.8	2 ± 0.4	2.2 ± 0.6	3.70 ± 0.9	1.92 ± 0.98	3.91 ± 1	1.99 ± 1.1
TSH μU/mL	5.31 ± 2.5	P = .01				P = .03		P = .03
FT4 ng/dL	1.30 ± 0.17	1.19 ± 0.39	1 ± 0.38	1.0 ± 0.2	1.31 ± 0.9	1.22 ± 0.98	1.32 ± 1	1.24 ± 0.99
FT4 ng/dL	1.30 ± 0.17	P = .04				P = .2		P = .2
%EWL	67.5 ± 16.3				69.4 ± 22.3		69.1 ± 1.4

n, number of patients seen LSG.

Group A, received hormone treatment; Group B, received no treatment; %EWL, excess weight loss (significant = P < .05).

Bold values indicate statistical significance.

BMI, body mass index; SCH, subclinical hypothyroidism; TSH, thyroid stimulating hormone.

Table 3.

Correlation Between Body Mass Index and Thyroid Hormones Changes at 12 Months After Laparoscopic Sleeve Gastrectomy

	Group I		Group II		Group III
	<40		40–50		>50
BMI (kg/m²)	Preoperative n = 64	12 months n = 55	Preoperative n = 448	12 months n = 390	Preoperative n = 42	12 months n = 36
TSH μU/mL	3.1 ± 1.4	1.1 ± 0.9	3.9 ± 1.3	1.99 ± 1	4.1 ± 1.9	1.89 ± 0.98
TSH μU/mL	3.1 ± 1.4	P = .04		P = .03		P = .01
FT4 ng/dL	1.30 ± 0.98	0.99 ± 0.67	1.30 ± 1.1	1.3 ± 0.99	1.28 ± 0.88	1.1 ± 0.71
FT4 ng/dL	1.30 ± 0.98	P > .05		P > .05		P > .05

Significant = P < .05.

Bold values indicate statistical significance.

BMI, body mass index; TSH, thyroid stimulating hormone.

Discussion

The incidence of SCH in the normal population varies between 4% and 9%, and is more common in women than in men^7,8; in morbidly obese patients this incidence is higher (10.5%, 25%).^9,10 Among the 554 morbidly obese patients studied in this work there were 72 patients (12.9%) with SCH; this incidence confirms results described in several previous studies.^2,3,9

Some suggested that the increase in serum TSH in SCH cases is a progression to develop a symptomatic hypothyroidism and that weight loss after bariatric surgery can lead to either resolution or improvement in thyroid hormones levels.^9–11 Our study confirms this hypothesis and 1 year after LSG our SCH patients had a significant decrease in serum TSH and FT4 to within the normal range. The improvement in thyroid hormone levels after bariatric surgery and loss of weight is attributed to the decrease in serum leptin after weight loss.¹² High leptin levels appears to play a role in obesity-related SCH may be by resetting of the central thyrostat.¹³ Serum leptin has a close relationship with the hypothalamic–pituitary–thyroid axis and a suppressive effect on thyroid hormones synthesis and secretion.^10,13 The improvement in thyroid function after bariatric surgery is possibly due to resolution of these obesity-related adipokines. Euthyroid patients in this study had also a significant decrease in serum TSH levels at 12 months post-LSG, whereas the change in serum FT4 was insignificant. The drop in TSH levels in euthyroid patients could be explained by a possible alteration in the feedback regulation of the thyroid system.

At 6 months post-LSG resolution of SCH occurred in 63 of the 66 patients who attended for follow-up, the remaining three cases just improved (these had significantly higher preoperative serum TSH and BMI, but thyroid antibodies were within normal). At 12 months complete resolution of SCH occurred in all our cases. Our results are comparable with previously published results that showed normalization of serum TSH after bariatric surgery. A remission rate of 100% was previously noted after banding and Roux-en-y gastric bypass (RYGB).^9,10 Janssen et al. study on morbidly obese patients with a mean BMI of 45 kg/m² reported 14% incidence of SCH and normalization of serum TSH in 90% of these cases 1 year after RYGB.⁸ comparable results were described after Roux-en-Y gastric bypass^9,10 and LSG.¹¹

At 12 months post-LSG in this study there was a significant decrease in the mean BMI in the SCH and in the euthyroid patients. The postoperative %EWL was also significant and comparable with the results reported in the literature.¹⁴ A statistically significant positive relation between BMI and serum TSH levels was noticed in all the study cohort, and patients with higher BMI (>40) had a significantly higher mean serum TSH compared with patients with BMI (<40). The relation between BMI and FT4 was, however, insignificant. These results confirm the results obtained in previous studies.^2,3,10

When we examined the outcome of our SCH patients after LSG in this study there was no significant difference in the postoperative changes in BMI, serum TSH, and FT4 between SCH patients who received weight adjusted dose of levothyroxine (35 patients) and those who did not receive any treatment (37 patients); adding thyroxine treatment did not improve outcome after LSG and weight loss.

Thyroxine treatment for SCH cases is a subject of debates. Theoretical reasons for treatment were to avoid progression to symptomatic hypothyroidism and avoid the increased level of TSH, which is linked to decreased lipid and carbohydrate metabolism with its negative impact on obesity.¹⁰ Other reasons for treatment is the increased mortality and cardiovascular risks (10%–20%) associated with SCH,^8,15 as well as the fear that SCH patients may not lose weight after bariatric surgery similar to euthyroid patients because of the positive correlation between TSH and BMI. Another concern in favor for thyroxine treatment is that the increase in serum TSH may be due to underlying Hashimoto thyroiditis; all these fears were not present in this study. In contrast, in favor of giving no treatment is that most SCH were controlled at 12 months after LSG as in the present and previous studies. Villar et al. found that thyroxine treatment for SCH in general population did not improve survival or decrease cardiovascular comorbidity.^7,16 Also in favor of giving no treatment is the fact that weight loss after bariatric surgery for SCH and euthyroid patients is comparable and there is no increased risk of Hashimoto disease in SCH cases (thyroid antibodies prevail equally in SCH and in euthyroid cases).^8,17 The high rate of TSH normalization after bariatric surgery found in the present and previous studies suggest that SCH is a consequence and not a cause of obesity.¹²

Currently, the suggested practical approach is routine levothyroxine therapy for persons with a persistent serum TSH of >10.0 μU/mL, these patients have 75% chance to develop symptomatic hypothyroidism; greater TSH level predicts higher rate of progression to overt hypothyroidism, whereas patients with lower TSH levels are less likely to progress.¹⁸ Treatment for patients with serum TSH between 5 and 10 μU/mL, however, remains controversial (80% of SCH patients have TSH <10 μU/mL); decision for levothyroxine therapy for this group should be individualized (on a case-by-case basis) and depends on the age of the patient, degree of TSH elevation, persistence and gradual increase of TSH, positive antithyroid antibodies, and presence of goiter.

One can thus suggest that apart from specific clinical situation where it is better to start thyroxine treatment (positive antithyroid antibodies, dyslipidemia, and progressive TSH increase) thyroxine treatment in SCH may play a role if TSH is >10 mU/L and in patients who do not improve after bariatric surgery. The balance of risk and benefit is thus influenced by the degree of TSH elevation, associated risk factors, and comorbidities.¹⁶ Our findings could be a little contribution to previously published data showing that weight loss after bariatric surgery may help in resolution of SCH.

The limitations in this study are the small number of SCH cases. A larger study with longer follow-up will be valuable to confirm our results and to assess the persistence of these results. Some factors such as leptin were not assessed.

Conclusion

The incidence of SCH in the studied morbidly obese patients was 12.9%. LSG leads to significant decrease in BMI associated with a significant decrease in serum TSH. Postoperative normalization of serum TSH was more pronounced in SCH patients and those with higher preoperative BMI. At 6 months post-LSG, SCH resolved in 95.45% and complete resolution occurred at 12 months. Adding levothyroxine treatment in obese SCH patients did not improve outcome and should be reserved to specific clinical and laboratory indications. Follow-up for these cases rather than active hormonal treatment could be suggested.

Author's Contributions

Data analysis and article writing was done by all authors. Laboratory investigations were supervised and analyzed by M.B.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received.

References

Pucci

, Chiovato

, Pinchera

. Symposium 8. Thyroid function and iodothyronine and peripheral action and metabolism: Thyroid and lipid metabolism. Int J Obes, 2000; 24:S10912.

Nyrnes

, Jorde

, Sundsfjord

. Serum TSH is positively associated with BMI. Int J Obes, 2006; 30:100–105.

Iacobellis

, Ribaudo

, Zappaterreno

, et al. Relationship of thyroid function with body Mass Index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol, 2005; 62:487–491.

Adlin

. Subclinical hypothyroidism: Deciding when to treat. Am Fam Physician, 1998; 57:776–780.

Ekins

, Ellis

. The radioimmunoassay of free thyroid hormones in serum. In: Robins

, Braveman

(eds). Thyroid research. Proceedings of the Seventh International Thyroid Conference, Boston. Amsterdam: Excepta Medical, 1975, p. 597.

Rodondi

, Newman

, Vittinghoff

, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med, 2005; 165:2460–2466.

Villar

, Saconato

, Valente

, Atallah

. Thyroid hormone replacement for Subclinical hypothyroidism. Cochrane Database Syst Rev, 2007; 18:CD003419.

Janssen

, Homan

, Schijns

, et al. Subclinical hypothyroidism and its relation to obesity in patients before and after Roux-en-Y gastric bypass. Surg Obes Relat Dis, 2015; 11:1257–1263.

Moulin de Moraes

, Mancini

, de Melo

, et al. Prevalence of subclinical hypothyroidism in a morbidly obese population and improvement after weight loss induced by Roux-en-Y gastric bypass. Obes Surg, 2005; 15:1287–1291.

10.

Chikunguwo

, Brethauer

, Nirujogi

, et al. Influence of obesity and surgical weight loss on thyroid hormone levels. Surg Obes Relat Dis, 2007; 3:631–635; discussion 5–6.

11.

Ruiz-Tovar

, Boix

, Galindo

, et al. Evolution of subclinical hypothyroidism and its relation with glucose and triglycerides levels in morbidly obese patients after undergoing sleeve gastrectomy as bariatric procedure. Obes Surg, 2014; 24:791–795.

12.

Rosenbaum

, Nicolson

, Hirsch

, Murphy

, Chu

, Leibel

. Effects of weight change on Plasma leptin concentrations and energy expenditure. J Clin Endocrinol Metab, 1997; 82:3647–3654.

13.

Flier

, Harris

, Hollenberg

. Leptin, nutrition, and the thyroid: The why, the wherefore, and the wiring. J Clin Invest, 2000; 105:859–861.

14.

Deitel

, Gagner

, Erickson

, Crosby

. Third International Summit: Current status of sleeve gastrectomy. Surg Obes Relat Dis, 2011; 7:749–759.

15.

Rotondi

, Leporati

, La Manna

, et al. Raised serum TSH levels in patients with morbid obesity: Is it enough to diagnose subclinical hypothyroidism?. Eur J Endocrinol, 2009; 160:403–408.

16.

Jebasingh

, Naik

, Thomas

. Subclinical hypothyroidism. Curr Med Issues, 2018; 16:39–41.

17.

Ochs

, Auer

, et al. Meta-analysis: Subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med, 2008; 148:832–845.

18.

Vahab

. Subclinical hypothyroidism: An update for primary care physicians. Mayo Clin Proc, 2009; 84:65–71.