World J Surg DOI 10.1007/s00268-014-2646-4
Laparoscopic Sleeve Gastrectomy Leads to Reduction in Thyroxine Requirement in Morbidly Obese Patients With Hypothyroidism Sandeep Aggarwal • Shrey Modi • Toney Jose
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Background The impact of laparoscopic sleeve gastrectomy (LSG) on various co-morbidities including type II diabetes mellitus, hypertension, and sleep apnea is well established. However, its effect on hypothyroidism has not been given due attention evidenced by the scant literature on the subject. The purpose of this report is to assess the change in thyroxine (T4) requirement in morbidly obese patients with clinical hypothyroidism after LSG. Methods We conducted a retrospective review of morbidly obese patients on T4 replacement therapy for clinical hypothyroidism who underwent LSG from August 2009 to July 2012 at our institution. Results Of the 200 patients who underwent LSG during this period, 21 (10.5 %) were on T4 replacement therapy preoperatively for clinical hypothyroidism. Two patients were lost to follow-up. The remaining 19 patients were categorized into two groups. Group 1 comprised 13 patients with decreased T4 requirements after LSG. Group 2 comprised six patients in whom the T4 dose remained unaltered. The mean change in T4 requirement in group 1 was 42.07 % (12–100 %). Group 1 patients had a significantly higher mean preoperative body mass index (48.7 vs. 43.0 kg/m2; p = 0.03) than the group 2 patients. There was a significant correlation between the percentage excess weight loss and the percentage change in T4 requirement in group 1 (r = 0.607, p = 0.028). Conclusions Sleeve gastrectomy has a favorable impact on hypothyroid status as seen by a reduction in T4
S. Aggarwal (&) S. Modi T. Jose Department of Surgical Disciplines, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India e-mail: [email protected]
requirement in the majority of morbidly obese patients with overt hypothyroidism.
Introduction There is an increased prevalence of hypothyroidism among obese populations [1, 2]. Obese individuals have relative resistance to thyroxine (T4), resulting in increased levels of serum thyrotropin, TSH [2]. Another possible explanation is that such an increase may be an adaptive response to chronic nutrient surfeit because T4 increases resting energy expenditure (REE), diminishing the available energy for accumulation in fats [3]. Weight loss surgery such as laparoscopic Roux-en-Y gastric bypass (LRYGB) has been reported to result in a reduced T4 replacement dose in hypothyroid patients [4, 5]. Laparoscopic sleeve gastrectomy (LSG) has also been shown to affect thyroid hormone kinetics [6], although its impact on changes in T4 requirement has not been reported. The present report focuses on the change in T4 replacement dosage as a marker for an effect on hypothyroidism in obese patients with overt hypothyroidism undergoing LSG.
Materials and methods We conducted a retrospective cohort study with observational characteristics from the August 2009 to July 2012. Of the 200 morbidly obese patients who underwent LSG during this period, 21 patients were found to be on T4 replacement preoperatively for overt hypothyroidism. Patients determined to have subclinical hypothyroidism during preoperative evaluation were excluded from the study. Of the 21 patients, 19 were available for follow-up.
123
World J Surg
We reviewed the data for these patients regarding preoperative body weight, body mass index (BMI), percent excess weight loss (%EWL), duration of hypothyroidism, and change in T4 requirements following LSG. A multidisciplinary team evaluated all patients preoperatively. A single surgeon performed the surgery in all cases.
for relevant data using Student’s t-test. Correlation was tested using Pearson’s correlation. Analysis was done using Statistical Package for the Social Sciences version 16 (SPSS, Chicago, IL, USA).
Results Surgical technique
Parameters of a frequency distribution curve were calculated (as the mean and range). The p value was calculated
Among the 200 patients who underwent LSG for morbid obesity during the study period, 21 (10.5 %) were being treated preoperatively for overt hypothyroidism with T4. The mean length of follow-up was 18 months (range 3–36 months). Two patients were lost to follow-up. Among the remaining 19 patients, the mean age was 38.73 years (range 17–60 years), and the mean preoperative BMI was 46.96 kg/m2 (range 37.0–62.8 kg/m2). Mean preoperative excess body weight was 52.4 kg (range 31.7–93.3 kg). The T4 dose could be reduced in 13 patients (68.4 %) at varying time intervals after LSG. One patient (5.2 %), a 32-year-old woman with preoperative BMI of 48.5 kg/m2 and daily preoperative T4 requirement of 150 lg was off replacement T4 at 12 months after the surgery. Of the 19 patients, 6 (31.6 %) had no change in their T4 requirement. The mean change and percentage change in T4 requirement for the whole cohort were 36.15 ± 39.74 lg (range 0–150 lg) and 28.78 ± 28.20 % (range 0–100 %), respectively. The mean absolute change and percentage change in T4 requirement among 13 patients with postoperative reduction in T4 requirement (group 1) were 52.84 ± 37.59 lg (range 12–150 lg) and 42.07 ± 24.23 % (range 12–100 %), respectively. Characteristics of the patients with reduced T4 requirement (group 1) and those with unchanged T4 requirement (group 2) in relation to age, sex, preoperative BMI, length of follow-up, mean %EWL, duration of hypothyroidism, and preoperative T4 dose are given in Table 1. Patients in group 1 had a significantly higher mean preoperative BMI (48.7 vs. 43 kg/m2; p = 0.03) than the group 2 patients. T4 requirement did not correlate well with absolute weight loss, but there was a significant correlation between the
Table 1 Patient characteristics
Whole cohort
The sleeve was performed in a standard way. Four ports were used: three 12 mm and one 5 mm. A self-retaining liver retractor was introduced through a 5-mm incision in the epigastrium. The greater omentum was detached from a point 4 cm from the pylorus up to the angle of His using either ultrasonic shears or a bipolar sealing device. The left crus was completely exposed up to the medial border. A sleeve was created over a 36F gastric calibration tube with sequential firings of a three-row stapler. The staple line reinforcement was done as needed, not routinely. In effect, we created a narrow gastric tube by removing a major portion of the stomach along the greater curvature. Thus, using a minimally invasive technique and without altering the natural anatomy of the digestive tract, we reduced the capacity of the stomach to 100–150 mL. Follow-up The patients are followed up at 1 week, 1 month, and then at 3-month intervals for the first year and then yearly. In addition to routine nutritional screening, thyroid function tests were obtained at 3, 6, and 12 months and yearly thereafter. The T4 dose was reduced in patients with deranged thyroid function tests on follow-up in consultation with the endocrinologist. Statistical analysis
Characteristics
(n = 19)
BMI body mass index, %EWL percent excess weight loss
123
Group 1: improved thyroid status (n = 13)
Group 2: unchanged thyroid status (n = 6)
p
Age (years)
38.7
40.4
35.1
NS
Sex (F/M)
16/3
12/1
4/2
NS
BMI (kg/m2)
46.9
48.7
43
0.03
Hypothyroidism present (years)
9.5
9.6
10
NS
Follow-up (months)
18
18.6
16.5
NS
%EWL
62.2
66.9
52
NS
Preoperative thyroxine dose (lg)
111.80
121.10
91.60
NS
Postoperative thyroxine dose (lg)
75.65
68.30
91.60
World J Surg 120
Percent EWL
100 80 60
r= 0.607, p=0.028
40 20 0 0
20
40
60
80
100
120
Percent change in thyroxine
Fig. 1 Correlation between percent excess weight loss (EWL) and percent change in thyroxine in the group 1 patients
%EWL and percent change in T4 requirement in group 1 patients (Fig. 1).
Discussion Obesity is associated with increased prevalence of hypothyroidism [1, 2]. Increased levels of TSH have been found in obese persons [2, 7], which correlates positively with the percentage body fat and plasma leptin levels [7]. This can be explained by the fact that obesity is associated with increased leptin levels [7]. Leptin not only has direct excitatory effects on the hypothalamic–pituitary–thyroid axis in the fed state but also acts in a paracrine/autocrine fashion in the anterior pituitary to decrease TSH secretion. However, leptin’s stimulatory hypothalamic action on thyrotropin releasing hormone neurons overrides its direct pituitary inhibitory effect on TSH release [8]. In addition to the central interaction between thyroid and leptin physiology, there might also be a peripheral relation between them because of their involvement in mitochondrial uncoupling and thermogenesis [9]. A change in the pattern of fat deposition also alters the response of adiposity to thyroid hormones. Visceral abdominal fat has fewer T4 receptors than subcutaneous adipose tissue, contributing to the relative resistance to T4 and therefore increased TSH and T4 levels in obese patients [10]. In addition, T4 increases the basal metabolic rate and consequently the REE, leading to decreased availability of excess energy for synthesis of fat [3, 11]. Therefore, increases in thyroid hormone levels and TSH in the presence of obesity might be an adaptive process. In our series, LSG led to decreased T4 requirement in 13 patients (68.4 %). During follow-up, the thyroid function tests revealed very low TSH values (\0.3 mIU/L), and some of these patients complained of palpitations and
shakiness. The supplemental T4 dose was gradually reduced, and serial TSH assays were continued until the TSH value reached a mid-normal range (i.e., 2.0–3.0 mIU/ L; normal 0.3–5.5 mIU/L). Improved thyroid status has been reported among obese hypothyroid patients following other bariatric surgical procedures [4, 5, 12, 13]. In a series of 20 morbidly obese patients with clinical hypothyroidism who underwent LRYGB, hypothyroidism improved in 7 (35 %) and complete resolution in 5 (25 %) [4]. According to the authors, weight loss following surgery led to improved peripheral hormone resistance resulting in improved thyroid function and diabetes mellitus. Interestingly, there was worsened thyroid function in 5 (25 %) patients, all of whom had autoimmune hypothyroidism. The worsening was attributed to alleviation of immune dysfunction following weight loss after surgery. However, there was no significant difference in the mean preoperative BMI between patients whose thyroid function had improved, those in whom it was unchanged, or those in whom it had worsened. In our series, the mean preoperative BMI was higher in the patients whose T4 requirements could be reduced after LSG. In a series of 224 patients who underwent LRYGB, clinical hypothyroidism was present in 23 (10.2 %) [5]. Improvement in hypothyroidism occurred in 10 (43 %) with complete resolution in 2 (8 %) patients. No significant difference in weight loss was found between patients with improved or unchanged thyroid function, but patients with complete or nearly complete EWL had a greater reduction in T4 requirement, possibly due to improved thyroid hormone resistance following weight loss. Yashkov et al. [12], in a series of 48 morbidly obese patients who underwent vertical banded gastroplasty, noted that after EWL the TSH level dropped significantly with no changes in free triiodothyronine (FT3) and free T4 (FT4) concentration. Dall’Asta et al. [13] suggested a decrease in deiodinase level to account for the reduction in FT3 and FT3/FT4 and an alteration in the hypothalamic–thyroid axis following laparoscopic gastric banding possibly due to deficient calorie intake-induced weight loss. It has been reported that levo-T4 pharmacokinetic parameters improve following LSG, whereas they remain the same after LRYGB [6]. Lips et al., in a comparative study of weight loss induced by restrictive and malabsorption procedures concluded that weight loss directly influences thyroid hormone regulation independently of the strategy used. Their proposed mechanism was the same as discussed earlier based on leptin’s role and peripheral hormone metabolism [14]. Based on these studies, it is proposed that LSG can be a suitable weight loss procedure in clinically hypothyroid, morbidly obese individuals. In our study, there was a significant difference in the mean preoperative BMI in patients in whom T4 requirement
123
World J Surg
decreased and those in whom it remained unchanged. The possible explanation could be that the hypothyroidism in obese individuals is partly mediated by peripheral hormone resistance [15, 16]. Thus, obesity induces a state of thyroid hormone resistance similar to insulin resistance [2]. Individuals with higher preoperative BMIs have greater peripheral hormone resistance, resulting in greater T4 replacement requirements. Increased levels of nonesterified fatty acid levels are found in the presence of obesity that inhibit T4 binding in the pooled serum, as was shown in an animal model [17]. This could be another mechanism for peripheral hormone resistance that results in higher T4 levels in the circulation to counteract this effect. In our group 1 patients, the reduced T4 dose correlated well with the %EWL. This correlation has not been reported in other studies. Following LSG, obese individuals undergo substantial weight loss. It then leads to decreased peripheral hormone resistance and a resultant decrease in the need for T4 replacement. Therefore, it is appropriate to infer that in obese hypothyroid patients obesity is the cause of hypothyroidism rather than being the consequence of it. In patients with unchanged thyroid function, however, there may be other factors, including autoimmune thyroid disorders, that cause a hypothyroid state. Weight loss following LSG does not lead to alleviation of the hypothyroidism in such patients [4]. A major limitation of our study is the relatively small sample size, which accounts for the wide range of data.
Conclusions LSG has a favorable impact on hypothyroidism and results in a reduction in T4 requirement after surgery in a majority of patients with clinical hypothyroidism.
Conflict of interest The authors declare that there are no areas of potential or real conflict.
References 1. Fierabracci P, Pinchera A, Martinelli S et al (2011) Prevalence of endocrine diseases in morbidly obese patients scheduled for bariatric surgery: beyond diabetes. Obes Surg 21:54–60
123
2. Michalaki MA, Vagenakis AG, Leonardou AS et al (2006) Thyroid function in humans with morbid obesity. Thyroid 16:73–78 3. Danforth E Jr, Horton ES, O’Connell M et al (1979) Dietaryinduced alterations in thyroid hormone metabolism during overnutrition. J Clin Investig 64:1336–1347 4. Fazylov R, Soto E, Cohen S et al (2008) Laparoscopic Roux-en-Y gastric bypass surgery on morbidly obese patients with hypothyroidism. Obes Surg 18:644–647 5. Raftopoulos Y, Gagne´ DJ, Papasavas P et al (2004) Improvement of hypothyroidism after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Obes Surg 14:509–513 6. Gkotsina M, Michalaki M, Mamali I et al (2013) Improved levothyroxine pharmacokinetics after bariatric surgery. Thyroid 23:414–419 7. Pinkney JH, Goodrick SJ, Katz J et al (1998) Leptin and the pituitary thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects. Clin Endocrinol (Oxf) 49:583–588 8. Ortiga-Carvalho TM, Oliveira KJ, Soares BA et al (2002) The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol 174:121–125 9. Zimmermann-Belsing T, Brabant G, Holst JJ et al (2003) Circulating leptin and thyroid dysfunction. Eur J Endocrinol 149:257–271 10. Ortega FJ, Moreno-Navarrete JM, Ribas V et al (2009) Subcutaneous fat shows higher thyroid hormone receptor-alpha1 gene expression than omental fat. Obesity 17:2134–2141 11. Reinehr T (2010) Obesity and thyroid function. Mol Cell Endocrinol 316:165–171 12. Yashkov YI, Vinnitsky LI, Poroykova MV et al (2000) Some hormonal changes before and after vertical banded gastroplasty for severe obesity. Obes Surg 10:48–53 13. Dall’Asta C, Paganelli M, Morabito A et al (2010) Weight loss through gastric banding: effects on TSH and thyroid hormones in obese subjects with normal thyroid function. Obesity 18:854–857 14. Lips MA, Pijl H, van Klinken JB et al (2013) Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects. Eur J Endocrinol 169:339–347 15. Lacobellis G, Ribaudo MC, Zappaterreno A et al (2005) Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol (Oxf) 62:487–491 16. Rosenbaum M, Hirsch J, Murphy E et al (2000) Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr 71:1421–1432 17. Ferguson DC, Caffall Z, Hoenig M (2007) Obesity increases free thyroxine proportionally to non-esterified fatty acid concentrations in adult neutered female cats. J Endocrinol 194:267–273
Laparoscopic Sleeve Gastrectomy Leads to Reduction in Thyroxine Requirement in Morbidly Obese Patients With Hypothyroidism Sandeep Aggarwal • Shrey Modi • Toney Jose
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Background The impact of laparoscopic sleeve gastrectomy (LSG) on various co-morbidities including type II diabetes mellitus, hypertension, and sleep apnea is well established. However, its effect on hypothyroidism has not been given due attention evidenced by the scant literature on the subject. The purpose of this report is to assess the change in thyroxine (T4) requirement in morbidly obese patients with clinical hypothyroidism after LSG. Methods We conducted a retrospective review of morbidly obese patients on T4 replacement therapy for clinical hypothyroidism who underwent LSG from August 2009 to July 2012 at our institution. Results Of the 200 patients who underwent LSG during this period, 21 (10.5 %) were on T4 replacement therapy preoperatively for clinical hypothyroidism. Two patients were lost to follow-up. The remaining 19 patients were categorized into two groups. Group 1 comprised 13 patients with decreased T4 requirements after LSG. Group 2 comprised six patients in whom the T4 dose remained unaltered. The mean change in T4 requirement in group 1 was 42.07 % (12–100 %). Group 1 patients had a significantly higher mean preoperative body mass index (48.7 vs. 43.0 kg/m2; p = 0.03) than the group 2 patients. There was a significant correlation between the percentage excess weight loss and the percentage change in T4 requirement in group 1 (r = 0.607, p = 0.028). Conclusions Sleeve gastrectomy has a favorable impact on hypothyroid status as seen by a reduction in T4
S. Aggarwal (&) S. Modi T. Jose Department of Surgical Disciplines, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India e-mail: [email protected]
requirement in the majority of morbidly obese patients with overt hypothyroidism.
Introduction There is an increased prevalence of hypothyroidism among obese populations [1, 2]. Obese individuals have relative resistance to thyroxine (T4), resulting in increased levels of serum thyrotropin, TSH [2]. Another possible explanation is that such an increase may be an adaptive response to chronic nutrient surfeit because T4 increases resting energy expenditure (REE), diminishing the available energy for accumulation in fats [3]. Weight loss surgery such as laparoscopic Roux-en-Y gastric bypass (LRYGB) has been reported to result in a reduced T4 replacement dose in hypothyroid patients [4, 5]. Laparoscopic sleeve gastrectomy (LSG) has also been shown to affect thyroid hormone kinetics [6], although its impact on changes in T4 requirement has not been reported. The present report focuses on the change in T4 replacement dosage as a marker for an effect on hypothyroidism in obese patients with overt hypothyroidism undergoing LSG.
Materials and methods We conducted a retrospective cohort study with observational characteristics from the August 2009 to July 2012. Of the 200 morbidly obese patients who underwent LSG during this period, 21 patients were found to be on T4 replacement preoperatively for overt hypothyroidism. Patients determined to have subclinical hypothyroidism during preoperative evaluation were excluded from the study. Of the 21 patients, 19 were available for follow-up.
123
World J Surg
We reviewed the data for these patients regarding preoperative body weight, body mass index (BMI), percent excess weight loss (%EWL), duration of hypothyroidism, and change in T4 requirements following LSG. A multidisciplinary team evaluated all patients preoperatively. A single surgeon performed the surgery in all cases.
for relevant data using Student’s t-test. Correlation was tested using Pearson’s correlation. Analysis was done using Statistical Package for the Social Sciences version 16 (SPSS, Chicago, IL, USA).
Results Surgical technique
Parameters of a frequency distribution curve were calculated (as the mean and range). The p value was calculated
Among the 200 patients who underwent LSG for morbid obesity during the study period, 21 (10.5 %) were being treated preoperatively for overt hypothyroidism with T4. The mean length of follow-up was 18 months (range 3–36 months). Two patients were lost to follow-up. Among the remaining 19 patients, the mean age was 38.73 years (range 17–60 years), and the mean preoperative BMI was 46.96 kg/m2 (range 37.0–62.8 kg/m2). Mean preoperative excess body weight was 52.4 kg (range 31.7–93.3 kg). The T4 dose could be reduced in 13 patients (68.4 %) at varying time intervals after LSG. One patient (5.2 %), a 32-year-old woman with preoperative BMI of 48.5 kg/m2 and daily preoperative T4 requirement of 150 lg was off replacement T4 at 12 months after the surgery. Of the 19 patients, 6 (31.6 %) had no change in their T4 requirement. The mean change and percentage change in T4 requirement for the whole cohort were 36.15 ± 39.74 lg (range 0–150 lg) and 28.78 ± 28.20 % (range 0–100 %), respectively. The mean absolute change and percentage change in T4 requirement among 13 patients with postoperative reduction in T4 requirement (group 1) were 52.84 ± 37.59 lg (range 12–150 lg) and 42.07 ± 24.23 % (range 12–100 %), respectively. Characteristics of the patients with reduced T4 requirement (group 1) and those with unchanged T4 requirement (group 2) in relation to age, sex, preoperative BMI, length of follow-up, mean %EWL, duration of hypothyroidism, and preoperative T4 dose are given in Table 1. Patients in group 1 had a significantly higher mean preoperative BMI (48.7 vs. 43 kg/m2; p = 0.03) than the group 2 patients. T4 requirement did not correlate well with absolute weight loss, but there was a significant correlation between the
Table 1 Patient characteristics
Whole cohort
The sleeve was performed in a standard way. Four ports were used: three 12 mm and one 5 mm. A self-retaining liver retractor was introduced through a 5-mm incision in the epigastrium. The greater omentum was detached from a point 4 cm from the pylorus up to the angle of His using either ultrasonic shears or a bipolar sealing device. The left crus was completely exposed up to the medial border. A sleeve was created over a 36F gastric calibration tube with sequential firings of a three-row stapler. The staple line reinforcement was done as needed, not routinely. In effect, we created a narrow gastric tube by removing a major portion of the stomach along the greater curvature. Thus, using a minimally invasive technique and without altering the natural anatomy of the digestive tract, we reduced the capacity of the stomach to 100–150 mL. Follow-up The patients are followed up at 1 week, 1 month, and then at 3-month intervals for the first year and then yearly. In addition to routine nutritional screening, thyroid function tests were obtained at 3, 6, and 12 months and yearly thereafter. The T4 dose was reduced in patients with deranged thyroid function tests on follow-up in consultation with the endocrinologist. Statistical analysis
Characteristics
(n = 19)
BMI body mass index, %EWL percent excess weight loss
123
Group 1: improved thyroid status (n = 13)
Group 2: unchanged thyroid status (n = 6)
p
Age (years)
38.7
40.4
35.1
NS
Sex (F/M)
16/3
12/1
4/2
NS
BMI (kg/m2)
46.9
48.7
43
0.03
Hypothyroidism present (years)
9.5
9.6
10
NS
Follow-up (months)
18
18.6
16.5
NS
%EWL
62.2
66.9
52
NS
Preoperative thyroxine dose (lg)
111.80
121.10
91.60
NS
Postoperative thyroxine dose (lg)
75.65
68.30
91.60
World J Surg 120
Percent EWL
100 80 60
r= 0.607, p=0.028
40 20 0 0
20
40
60
80
100
120
Percent change in thyroxine
Fig. 1 Correlation between percent excess weight loss (EWL) and percent change in thyroxine in the group 1 patients
%EWL and percent change in T4 requirement in group 1 patients (Fig. 1).
Discussion Obesity is associated with increased prevalence of hypothyroidism [1, 2]. Increased levels of TSH have been found in obese persons [2, 7], which correlates positively with the percentage body fat and plasma leptin levels [7]. This can be explained by the fact that obesity is associated with increased leptin levels [7]. Leptin not only has direct excitatory effects on the hypothalamic–pituitary–thyroid axis in the fed state but also acts in a paracrine/autocrine fashion in the anterior pituitary to decrease TSH secretion. However, leptin’s stimulatory hypothalamic action on thyrotropin releasing hormone neurons overrides its direct pituitary inhibitory effect on TSH release [8]. In addition to the central interaction between thyroid and leptin physiology, there might also be a peripheral relation between them because of their involvement in mitochondrial uncoupling and thermogenesis [9]. A change in the pattern of fat deposition also alters the response of adiposity to thyroid hormones. Visceral abdominal fat has fewer T4 receptors than subcutaneous adipose tissue, contributing to the relative resistance to T4 and therefore increased TSH and T4 levels in obese patients [10]. In addition, T4 increases the basal metabolic rate and consequently the REE, leading to decreased availability of excess energy for synthesis of fat [3, 11]. Therefore, increases in thyroid hormone levels and TSH in the presence of obesity might be an adaptive process. In our series, LSG led to decreased T4 requirement in 13 patients (68.4 %). During follow-up, the thyroid function tests revealed very low TSH values (\0.3 mIU/L), and some of these patients complained of palpitations and
shakiness. The supplemental T4 dose was gradually reduced, and serial TSH assays were continued until the TSH value reached a mid-normal range (i.e., 2.0–3.0 mIU/ L; normal 0.3–5.5 mIU/L). Improved thyroid status has been reported among obese hypothyroid patients following other bariatric surgical procedures [4, 5, 12, 13]. In a series of 20 morbidly obese patients with clinical hypothyroidism who underwent LRYGB, hypothyroidism improved in 7 (35 %) and complete resolution in 5 (25 %) [4]. According to the authors, weight loss following surgery led to improved peripheral hormone resistance resulting in improved thyroid function and diabetes mellitus. Interestingly, there was worsened thyroid function in 5 (25 %) patients, all of whom had autoimmune hypothyroidism. The worsening was attributed to alleviation of immune dysfunction following weight loss after surgery. However, there was no significant difference in the mean preoperative BMI between patients whose thyroid function had improved, those in whom it was unchanged, or those in whom it had worsened. In our series, the mean preoperative BMI was higher in the patients whose T4 requirements could be reduced after LSG. In a series of 224 patients who underwent LRYGB, clinical hypothyroidism was present in 23 (10.2 %) [5]. Improvement in hypothyroidism occurred in 10 (43 %) with complete resolution in 2 (8 %) patients. No significant difference in weight loss was found between patients with improved or unchanged thyroid function, but patients with complete or nearly complete EWL had a greater reduction in T4 requirement, possibly due to improved thyroid hormone resistance following weight loss. Yashkov et al. [12], in a series of 48 morbidly obese patients who underwent vertical banded gastroplasty, noted that after EWL the TSH level dropped significantly with no changes in free triiodothyronine (FT3) and free T4 (FT4) concentration. Dall’Asta et al. [13] suggested a decrease in deiodinase level to account for the reduction in FT3 and FT3/FT4 and an alteration in the hypothalamic–thyroid axis following laparoscopic gastric banding possibly due to deficient calorie intake-induced weight loss. It has been reported that levo-T4 pharmacokinetic parameters improve following LSG, whereas they remain the same after LRYGB [6]. Lips et al., in a comparative study of weight loss induced by restrictive and malabsorption procedures concluded that weight loss directly influences thyroid hormone regulation independently of the strategy used. Their proposed mechanism was the same as discussed earlier based on leptin’s role and peripheral hormone metabolism [14]. Based on these studies, it is proposed that LSG can be a suitable weight loss procedure in clinically hypothyroid, morbidly obese individuals. In our study, there was a significant difference in the mean preoperative BMI in patients in whom T4 requirement
123
World J Surg
decreased and those in whom it remained unchanged. The possible explanation could be that the hypothyroidism in obese individuals is partly mediated by peripheral hormone resistance [15, 16]. Thus, obesity induces a state of thyroid hormone resistance similar to insulin resistance [2]. Individuals with higher preoperative BMIs have greater peripheral hormone resistance, resulting in greater T4 replacement requirements. Increased levels of nonesterified fatty acid levels are found in the presence of obesity that inhibit T4 binding in the pooled serum, as was shown in an animal model [17]. This could be another mechanism for peripheral hormone resistance that results in higher T4 levels in the circulation to counteract this effect. In our group 1 patients, the reduced T4 dose correlated well with the %EWL. This correlation has not been reported in other studies. Following LSG, obese individuals undergo substantial weight loss. It then leads to decreased peripheral hormone resistance and a resultant decrease in the need for T4 replacement. Therefore, it is appropriate to infer that in obese hypothyroid patients obesity is the cause of hypothyroidism rather than being the consequence of it. In patients with unchanged thyroid function, however, there may be other factors, including autoimmune thyroid disorders, that cause a hypothyroid state. Weight loss following LSG does not lead to alleviation of the hypothyroidism in such patients [4]. A major limitation of our study is the relatively small sample size, which accounts for the wide range of data.
Conclusions LSG has a favorable impact on hypothyroidism and results in a reduction in T4 requirement after surgery in a majority of patients with clinical hypothyroidism.
Conflict of interest The authors declare that there are no areas of potential or real conflict.
References 1. Fierabracci P, Pinchera A, Martinelli S et al (2011) Prevalence of endocrine diseases in morbidly obese patients scheduled for bariatric surgery: beyond diabetes. Obes Surg 21:54–60
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2. Michalaki MA, Vagenakis AG, Leonardou AS et al (2006) Thyroid function in humans with morbid obesity. Thyroid 16:73–78 3. Danforth E Jr, Horton ES, O’Connell M et al (1979) Dietaryinduced alterations in thyroid hormone metabolism during overnutrition. J Clin Investig 64:1336–1347 4. Fazylov R, Soto E, Cohen S et al (2008) Laparoscopic Roux-en-Y gastric bypass surgery on morbidly obese patients with hypothyroidism. Obes Surg 18:644–647 5. Raftopoulos Y, Gagne´ DJ, Papasavas P et al (2004) Improvement of hypothyroidism after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Obes Surg 14:509–513 6. Gkotsina M, Michalaki M, Mamali I et al (2013) Improved levothyroxine pharmacokinetics after bariatric surgery. Thyroid 23:414–419 7. Pinkney JH, Goodrick SJ, Katz J et al (1998) Leptin and the pituitary thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects. Clin Endocrinol (Oxf) 49:583–588 8. Ortiga-Carvalho TM, Oliveira KJ, Soares BA et al (2002) The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol 174:121–125 9. Zimmermann-Belsing T, Brabant G, Holst JJ et al (2003) Circulating leptin and thyroid dysfunction. Eur J Endocrinol 149:257–271 10. Ortega FJ, Moreno-Navarrete JM, Ribas V et al (2009) Subcutaneous fat shows higher thyroid hormone receptor-alpha1 gene expression than omental fat. Obesity 17:2134–2141 11. Reinehr T (2010) Obesity and thyroid function. Mol Cell Endocrinol 316:165–171 12. Yashkov YI, Vinnitsky LI, Poroykova MV et al (2000) Some hormonal changes before and after vertical banded gastroplasty for severe obesity. Obes Surg 10:48–53 13. Dall’Asta C, Paganelli M, Morabito A et al (2010) Weight loss through gastric banding: effects on TSH and thyroid hormones in obese subjects with normal thyroid function. Obesity 18:854–857 14. Lips MA, Pijl H, van Klinken JB et al (2013) Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects. Eur J Endocrinol 169:339–347 15. Lacobellis G, Ribaudo MC, Zappaterreno A et al (2005) Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol (Oxf) 62:487–491 16. Rosenbaum M, Hirsch J, Murphy E et al (2000) Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr 71:1421–1432 17. Ferguson DC, Caffall Z, Hoenig M (2007) Obesity increases free thyroxine proportionally to non-esterified fatty acid concentrations in adult neutered female cats. J Endocrinol 194:267–273
