Zihni, Zihni, Karakose, Pülat, Ozcelik, Eken, Duran, and Uslu: An Evaluation of the Metabolic Profile in Total Thyroidectomy



Introduction

Thyroidectomy, meaning the complete or partial removal of a diseased thyroid gland, is still among the most frequently applied surgical interventions in general surgery clinics. The follow-up and treatment of complications which may develop associated with postoperative thyroid hormone changes is as important as attempting to prevent surgery-related complications following thyroidectomy [1-3].

Thyroid hormones expressed by the thyroid gland, are in a general sense, hormones which regulate basal metabolism. Thyroid hormones affect carbohydrate, protein, fat and calcium metabolism and the cardiovascular, gastro-intestinal, hematopoietic, pulmonary and neuromuscular systems. The effects of thyroid disease on the cardiovascular system have been investigated by many researchers. These studies have revealed various negative effects on the cardiovascular system of low or very high values of thyroid hormone levels [4]. In addition, there are various ongoing studies on the effects of low, normal or over-expression of these hormones on lipid metabolism and cholesterol levels. To date there have been few studies, although there is increasing interest in another subject, which is the changes observed in body weight, waist circumference and body mass index (BMI) values when there is thyroid hormone deficiency or excess [5, 6].

The definition of the collective risk factors is required for evaluation of the development of metabolic syndrome, Type 2 diabetes and cardiovascular complications. Previous prospective studies, using various definitions of metabolic syndrome, have suggested that the development of the syndrome is associated with a combination of factors. The factors focussed on are in particular insulin, obesity, lifestyle and healthcare habits. Reduced insulin sensitivity is thought to be at the forefront of the development of metabolic syndrome. Factors playing a role in the pathogenesis include obesity, insulin resistance, atherogenic dyslipidemia, inflammation due to coexisting morbidity, thrombosis and carcinogenesis [7-11].

The aim of this study was to investigate the changes in metabolic parameters and thyroid hormones despite thyroid replacement therapy following bilateral total thyroidectomy.

Material and Methods

The study comprised 36 patients who underwent bilateral total thyroidectomy in the General Surgery Clinic of Izmir Bozyaka Training and Research Hospital between October 2011 and May 2012. Informed consent was obtained from all patients. Evaluations of the patients were made preoperatively and at 6 months and 12 months postoperatively. Due to non-attendance of the 6-month follow-up appointment, 6 patients were withdrawn from the study.

All patients were evaluated preoperatively. Body mass index was calculated by recording height and weight of all patients, waist size was measured, arterial blood pressure was measured with a sphyngomanometer on the right arm after 10 mins of rest and a record was made of medications used. Peripheral blood samples were taken after 12-hour fasting for the analysis of low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TChol), triglyceride (TG), fasting glucose, fasting insulin, thyroid stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), C-reactive protein (CRP), and haemoglobin A1c (HbA1C) values. To evaluate insulin resistance, the homeostatic model assessment (HOMA-IR) test was used. The test was calculated according to the formula:

HOMA-IR = (Fasting insulin (mU/l) x fasting plasma glucose (mg/dl)) / 405

All patients started thyroid replacement therapy (L-thyroxin) 2 weeks postoperatively.

All these steps were repeated at the 6 and 12-month follow-up examinations. The data for each patient were recorded on a case report form.

Statistical Analysis

Statistical analysis was made using the SAS system program. Variance analysis was applied for the evaluation of continuous variables between groups. If the variance analysis was homogenous, repeated ANOVA was applied, and if not homgenous, the Friedman test. Subgroup analysis was made between paired groups and if the variance analysis was homogenous, repeated ANOVA was applied, and if not homgenous, the Wilcoxon score test. A value of p<0.05 was accepted as statistically significant in all the analyses.

Results

The basal characteristic properties of the patients were evaluated (Table 1). The patients were 25 females (83.3%) and 5 males (16.6%) with a mean age of 55±13.8 years. The diagnoses were hypertension in 12 (40%) patients, diabetes mellitus in 7 (23%), coronary artery disease in 2 (6.6%) and hyperlipidemia in 3 (10%). No chronic renal disease was found in any patient. Medications used by the patients were B-blockers in 4, (13.3%), ACE inhibitor or angiotensin receptor antagonist in 9 (29.9%), thyazide diuretics in 4 (13.3%), oral anti-diabetics in 6 (20%) and insulin in 1 (3.3%).

Table 1

Baseline characteristics.

Age 55 ± 13.8
Gender Female 25 (%83.3)
Male 5 (%16.6 )
Hypertension 12 (%40)
Diabetes mellitus 7 (%23)
Coronary artery disease 2 (%6.6)
Hyperlipidemia 3 (%10)
Used drugs
B-blockers 4 (%13.3)
ACEI/ARBs 9 (%29.9)
Thiazide diuretics 4 (%13.3)
Oral antidiabetic 6 (%20)
Insulin 1 (%3.3)

Note.

ACEI: angiotensin-coverting enzyme inhibitors;

ARBs: Angiotensin receptor blockers.

The patients were operated on for multinodular goitre (MNG) in 23 cases (76.6%), suspected malignancy of the nodule in 4 (13.3%) and Graves disease in 3 (10%). Preoperative and postoperative 6 and 12 months data analysis of the patients is shown in Table 2.

The TSH values were determined as pre-operative 1.20±3.45uIU/ml, postoperative 6th month, 1.28±15.3 uIU/ml and postoperative 12th month 1.65±8.4 uIU/ml, with no statistically significant difference between them.

The FT3 values were determined as preoperative 3.06±0.45 pg/ml, postoperative 6th month 2.79±0.53 pg/ml and postoperative 12th month, 2.8±0.29 pg/ml. Although a slight reduction was observed in the postoperative FT3 values, the difference between the preoperative and postoperative values was statistically significant.

The FT4 values were determined as preoperative 0.81±0.14 pg/ml, postoperative 6th month 0.96±0.27 pg/ml and postoperative 12th month, 0.98±0.2 pg/ml. Although a slight increase was observed in the postoeprative FT3 values, the difference between the preoperative and postoperative values was statistically significant (Table 2).

Table 2

Preoperative and 6th and 12th months postoperative data analysis.

Preoperative Postoperative (6th months) Postoperative (12th months) p1 p2 p3
TSH* (uIU/ml) 1.20±3.45 1.28±15.3 1.65±8.4 NS NS NS
FT3 (pg/ml) 3.06±0.45 2.79±0.53 2.8±0.29 0.02 0.006 NS
FT4 (ng/ml) 0.81±0.14 0.96±0.27 0.98±0.2 0.003 0.0002 NS
TChol (mg/dl) 191.2±31.7 204.7±32.8 203.9±27 0.008 0.02 NS
TG (mg/dl) 119.4±52.4 138±61.4 131.4±77.1 NS NS NS
HDL (mg/dl) 53.6±12.2 52.7±12.3 54±11.7 NS NS NS
LDL (mg/dl) 118±27 137.8±32.2 133.4±24.9 0.0003 0.002 NS
BMI (kg/m²) 29.2±4.8 30.05±5.05 29.9±4.9 0.0012 0.02 NS
Kilo (kg) 75.9±14.09 78.03±14.8 77.5±13.8 0.001 0.03 NS
Waist circumference (cm) 101.2±11.4 103.1±11.2 105.2±12 <0.001 <0.001 0.0019
Fasting glucose values * (mg/dl) 110.7±31.1 102±19.9 107.9±26.5 NS NS NS
Fasting insulin values * (uU/ml) 9.03±12.8 7.73±4.09 7.19±6.04 NS NS NS
HbA1c (%) 5.92±0.7 5.96±0.6 5.97±0.6 NS NS NS
HOMA-IR* 2.07±4.03 1.84±1.32 1.72±2.63 NS NS NS
CRP* (mg/dl) 1.56±3.57 0.33±0.2 0.31±0.61 0.005 <0.001 0.03
Systolic arterial blood (mmHg) 118.6±11.6 127.6±20 125.8±18.5 0.0014 0.0079 NS
Diastolic arterial blood (mmHg) 76±8.5 84.5±13.6 83.1±13.03 0.0006 0.0016 NS

Note.

p1: Preoperative - posptoperative (6th months);

p2: Preoperative- posptoperative (12th months);

p3: Postoperative (6th months) - postoperative (12th months);

NS: Not significant;

TSH: Thyroid stimulating hormone;

FT3: Free T3;

FT4: Free T4;

TChol: Total cholesterol;

TG: Triglyceride;

HDL: High-density lipoprotein;

LDL: Low-density lipoprotein;

BMI: Body mass index;

HOMA-IR: Homeostatic model assessment;

CRP: C-reaktive protein;

* Median values were used (after Friedman analysis), the average values were used for other values.

The TChol values were determined as preoperative 191.2±31.7mg/dl, postoperative 6th month 204.7±32.8 mg/dl, and postoperative 12th month, 203.9±27 mg/dl. When preoperative and postoperative values were compared, a statistically significant difference was determined, but the difference between the 6th and 12th months postoperatively was not statistically significant.

The TG values were determined as preoperative 119.4±52.4mg/dl, postoperative 6th month 138±61.4 mg/dl, and postoperative 12th month, 54±11.7 mg/dl and no statistically significant difference was determined.

The HDL values were determined as preoperative 53.6±12.2mg/dl, postoperative 6th month 52.7±12.3 mg/dl, and postoperative 12th month, 133.4±24.9 mg/dl and no statistically significant difference was determined.

The LDL values were determined as preoperative 118±27mg/dl, postoperative 6th month 137.8±32.2 mg/dl, and postoperative 12th month, 133.4±24.9 mg/dl. When preoperative and postoperative values were compared, a statistically significant increase was determined, but the difference between the 6th and 12th months postoperatively was not statistically significant.

The BMI values were determined as preoperative 29.2±4.8 kg/m2, postoperative 6th month 30.05±5.05 kg/m2 and postoperative 12th month, 29.9±4.9 kg/m2. Although a slight increase was observed in the postoperative BMI values, the difference between the preoperative and postoperative values was statistically significant. In addition, the body weights of the patients were determined as preoperative 75.9±14.09 kg, postoperative 6th month 78.03±14.8 kg and postoperative 12th month 77.5±13.8 kg. When preoperative and postoperative values were compared, a statistically significant increase was determined, but the difference between the 6th and 12th months postoperatively was not statistically significant. The waist circumference values were measured as preoperative 101.2±11.4 cm, postoperative 6th month 103.1±11.2 cm and postoperative 12th month 105.2±12 cm. The difference between preoperative and postoperative values was determined to be statistically significant (Table 2).

The fasting insulin values were determined as pre-operative 9.03±12.8uIU/ml, postoperative 6th month, 7.73±4.09 uIU/ml and postoperative 12th month 7.19±6.04 uIU/ml, with no statistically significant difference between them.

The HbA1c values of the patients were determined as pre-operative 5.92±0.7% postoperative 6th month, 5.96±0.6% and postoperative 12th month 5.97±0.6% with no statistically significant difference between them.

The HOMA-IR values were determined as pre-operative 2.07±4.03, postoperative 6th month, 1.84±1.32 and postoperative 12th month 1.72±2.63, with no statistically significant difference between them.

The CRP values were calculated as preoperative 1.56±3.57mg/dl, postoperative 6th month 0.33±0.2 mg/dl, and postoperative 12th month, 0.31±0.61 mg/dl and a statistically significant difference was determined in the comparison of the preoperative and postoperative values (Table 2).

The systolic arterial blood pressure values were measured as preoperative 118.6±11.6mmHg, postoperative 6th month 127.6±20mmHg, and postoperative 12th month, 125.8±18.5 mmHg. When preoperative and postoperative values were compared, a statistically significant increase was determined, but the difference between the 6th and 12th months postoperatively was not statistically significant.

The diastolic arterial blood pressure values were measured as preoperative 76±8.5mmHg, postoperative 6th month 84.5±13.6mmHg, and postoperative 12th month, 83.1±13.03 mmHg. When preoperative and postoperative values were compared, a statistically significant increase was determined, but the difference between the 6th and 12th months postoperatively was not statistically significant.

The fasting glucose values were determined as preoperative 110.7±31.1mg/dl, postoperative 6th month 102±19.9 mg/dl, and postoperative 12th month, 107.9±26.5 mg/dl and no statistically significant difference was determined (Table 2).

Discussion

In the this study the metabolic profiles of patients who underwent bilateral total thyroidectomy were examined preoperatively and in 6 and 12 months postoperatively. The aim of the study was to analyse changes developing in the postoerative period.

No statistically significant difference was determined between the preoperative TSH values and those at 6 and 12 months postoperatively. While a slight decrease in postoperative FT3 values was determined compared to the preoperative values, an increase was determined in the postoperative FT4 values. These changes are thought to be due to thyroid replacement therapy.

Various risk evaluation systems have been developed to be able to calculate the risk of a cardiovascular event developing in a healthy individual (myocardial infarction, stroke, atherosclerotic events which may lead to results such as sudden cardiac death). Some of these currently available systems are Framingham, SCORE, ASSIGN, Q-Risk, PROCAM and WHO [12, 13].

In a NHANES III study, 11611 healthy cases were separated into groups of low, moderate and high risk for a cardiovascular event. The Framingham risk evaluation system was developed based on the data of that study. The basis of the Framingham risk evaluation system is the evaluation of TChol, HDL, systolic blood pressure, age, gender, and cigarette use [14].

In 2004, the NHANES III study was re-analysed taking metabolic syndrome criteria into account. In cases determined with metabolic syndrome, the risk of myocardial infarction and /or stroke was determined to be significantly higher [15]. In a TEKHARF study conducted in Turkey, 53% of patients who developed coronary artery disease were determined to have metabolic syndrome [16].

In the dyslipidemia guidelines published by the European Cardiology Society (ESC) in 2011, the SCORE risk evaluation system was recommended for the prediction of cardiovascular events. By evaluating age, gender, TChol, HDL, systolic blood pressure and cigarette smoking, the 10-year development risk of an atherosclerotic event is calculated in this risk evaluation system. According to the risk scores, cases are separated into risk groups of low risk (estimated 10-year risk <1%), moderate risk (estimatd 10-year risk 1-4%), high risk (estimated 10-year risk 5-9%) and very high risk (estimated 10-year risk ≥10%). In addition, those with a previous diagnosis of coronary artery disease, or with Type 2 diabetes, or with moderate-severe chronic renal disease (glomerular filtration rate <60 ml/min/1.73 m²) are included in the very high risk group. After defining the risk levels, various treatment recommendations, primarily lifestyle changes to prevent cardiovascular events, are presented together with the treatment targets [17].

The results of the current study showed a significant increase over the postoperative year in TChol, LDL and TG levels, which have been correlated to the risk of a cardiovascular event, but no significant change was determined in HDL levels. It was also determined in the current study, that there was a significantly increasing trend in both systolic and diastolic arterial blood pressure values when preoperative values were compared with postoperative values.

Reduced sensitivity to insulin, or in other words, insulin resistance has been related in many studies with increased risk of atherosclerosis and carotid intima media thickness, even in healthy individuals [18, 19]. The method most widely used in clinical practice to determine insulin resistance is the HOMA-IR formula. In the current study, no statistically significant difference was determined between the HOMA-IR values calculated preoperatively and postoperatively. Furthermore, no significant difference was determined in respect of fasting glucose and HbA1c values in the comparison of preoperative and postoperative values. Although a slight reduction was determined in the fasting glucose levels of the patients postoperatively compared to the preoperativve levels, this was not statistically significant.

In a 2010 study by Özdemir et al, no change was determined in weight and BMI in 3 and 6 months follow-up in patients who had undergone total thyroidectomy for benign nodular goitre [20]. Similarly in the current study, no significant change was determined in BMI in the preoperative and postoperative periods. However, a significant increase was seen in the postoperative weight and waist circumference measurements compared to those of the preoperative period.

The CRP values, which had increased preoperatively because of the thyroid gland or environmental factors, showed a statistically significant fall postoperatively.

In several previous studies of hypothyroidic patients, a decrease in carotid intima media thickness and improvement in endothelial functions and the lipid profile have been shown after treatment with L-thyroxin [21-23]. In the current study, although euthyroid was achieved with L-thyroxin treatment, the disorder in the lipid profile continued in the postoperative 1-year follow-up period, systolic and diastolic arterial blood pressures increased and waist circumference values continued to increase. The negative effects of the metabolic profile of temporary hypothyroid (before starting thyroid replacement therapy) which develops in the postoperative acute period could still have an effect in the long-term despite later starting L-thyroxin therapy and this can be interpreted as L-thyroxin therapy remaining insufficient to reverse these negative effects.

Conclusion

The results of this study showed that even if euthyroid is achieved in patients following bilateral total thyroidectomy, the lipid profile, blood pressure and BMI values show negative changes in the postoperative period. Therefore, in postoperative follow-up, these parameters must be closely monitored in addition to the thyroid hormones and lifestyle changes should be implemented and where necessary, medical treatment.

References

1 

Agarwal G, Aggarwal V. Is total thyroidectomy the surgical procedure of choice for benign multinodular goiter? An evidence-based review. World J Surg. 2008;32:1313–1324. DOI: http://doi.org/10.1007/s00268-008-9579-8 [PMid: 18449595]

2 

Rios A, Rodriguez JM, Galindo PJ, Montoya MJ, Canteras M, Parrilla P. Surgical treatment of multinodular goiter in young patients. Endocrine. 2005;27:245–252. DOI: http://doi.org/10.1385/ENDO:27:3:245

3 

Delbridge L. Total thyroidectomy: the evolution of surgical technique. Aust N Z J Surg. 2003;73:761–768. DOI: http://doi.org/10.1046/j.1445-2197.2003.02756.x

4 

Dillman WH. Biochemical basis of thyroid hormone action in the heart. Am J Med. 1990;88:626–630. DOI: http://doi.org/10.1016/0002-9343(90)90530-Q

5 

Brent GA. The molecular basis of thyroid hormone action. N Engl J Med. 1994;1:847–853

6 

Chidakel A, Mentuccia D, Celi FS. Peripheral metabolism of thyroid hormone and glucose homeostasis. Thyroid. 2005;5:899–903. DOI: http://doi.org/10.1089/thy.2005.15.899 [PMid: 16131332]

7 

Knudsen N, Laurberg P, Rasmussen LB, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005;90:4019–4024. DOI: http://doi.org/10.1210/jc.2004-2225 [PMid: 15870128]

8 

Isik A, Karavas E, Peker K, Soyturk M, Yilmaz I. Male Mondor's Disease is a Rare Entity. Breast J. 2016 Nov;22(6):700–701. DOI: http://doi.org/10.1111/tbj.12657 [PMid: 27550206]

9 

Işık Arda, Fırat Deniz, Soyturk Mehmet, Demiryilmaz İsmail, Yilmaz İsmayil. İdiopatik Periportal Lenfadenopati. Gazi Medical Journal. 2016;27:51–52

10 

IŞIK Arda, SAYAR İlyas, GÜLHAN Barış, FIRAT Deniz. Fascioliasis: A Rare Case Mimicking Cholelithiasis. J Kartal TR. 2016;27(2):145–146

11 

Isik A, Eken H, Soyturk M, Firat D, Yilmaz I. A Rare Presentation of Accessory Breast in Axilla. Galician Medical Journal. 2016;23 (4):E201645 DOI: http://doi.org/10.21802/gmj.2016.4.5

12 

Cooney MT, Dudina AL, Graham IM. Value and limitations of existing scores for the assessment of cardiovascular risk. A review for clinicians. J Am Coll Cardiol. 2009;54:1209–1227. DOI: http://doi.org/10.1016/j.jacc.2009.07.020 [PMid: 19778661]

13 

Cooney MT, Dudina A, d'Agostino R, Graham IM. Cardiovascular risk estimation systems in primary prevention. Do they differ? Do they make a difference? Can we see the future? Circulation. 2010;122:300–310. DOI: http://doi.org/10.1161/CIRCULATIONAHA.109.852756 [PMid: 20644026]

14 

Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: Fourth Joint Task Force of the European Society of Cardiology and other societies. Eur J Cardiovasc Prev Rehabil. 2007;Suppl 2:S1–113. DOI: http://doi.org/10.1097/01.hjr.0000277983.23934.c9 [PMid: 17726407]

15 

İşgör A. Multinodüler guatr. In: İşgör A (Eds). Tiroid Hastalıkları ve Cerrahisi. İstanbul: Avrupa Tıp, 2000: 233-238.

16 

Arslan M, Atmaca A, Ayvaz G, et al. Metabolik Sendrom kılavuzu. Türkiye Endokrinoloji ve Metabolizma Derneği metabolik sendrom çalışma grubu 2009.

17 

Reiner Z, Catapono AL, De Backer G, et al. ESC/EAS Kılavuzları: Dislipidemilerin tedavisi. Avrupa Kardiyoloji Cemiyeti (ESC) ve Avrupa Ateroskleroz Derneği (EAS) Dislipidemilerin Tedavisi Görev Grubu. Türk Kardiyol Dern Arş. 2011;Suppl 3:10–14

18 

Kozakova M, Natali A, Dekker J, et al. Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study. Arterioscler Thromb Vasc Biol. 2013;33:1409–1417. DOI: http://doi.org/10.1161/ATVBAHA.112.300948 [PMid: 23599442]

19 

De Pergola G, Ciccone M, Pannacciulli N, et al. Lower insulin sensitivity as an independent risk factor for carotid wall thickening in normotensive, non-diabetic, non-smoking normal weight and obese premenopausal women. Int J Obes Relat Metab Disord. 2000;24:825–829. DOI: http://doi.org/10.1038/sj.ijo.0801239 [PMid: 10918528]

20 

Ozdemir S, Ozis E, Gulpinar K, Aydin TH, Suzen B, Korkmaz A. The effects of levothroxine substitution on body mass after total throidectomy for benign nodular goiter. Endocrine Regulations. 2010;44:147–153. DOI: http://doi.org/10.4149/endo_2010_04_147 [PMid: 21077724]

21 

Erbil Y, Ozbey N, Giriş M, Salmaslioğlu A, Ozarmağan S, Tezelman S. Effects of thyroxine replacement on lipid profile and endothelial function after thyroidectomy. Br J Surg. 2007;94:1485–1490. DOI: http://doi.org/10.1002/bjs.5915 [PMid: 17703499]

22 

Xiang GD, He YS, Zhao LS, Hou J, Yue L, Xiang HJ. Impairment of endothelium-dependent arterial dilation in Hashimoto's thyroiditis patients with euthyroidism. Clin Endocrinol. 2006;64:698–702. DOI: http://doi.org/10.1111/j.1365-2265.2006.02531.x [PMid: 16712674]

23 

Monzani F, Caraccio N, Kozakowa M, et al. Effect of levothyroxine replacement on lipid profile and intima–media thickness in subclinical hypothyroidism: a double-blind placebo-controlled study. J Clin Endocrinol Metab. 2004;89:2099–2106. DOI: http://doi.org/10.1210/jc.2003-031669 [PMid: 15126526]



Copyright (c) 2017 Ismail Zihni, Burcu Zihni, Oktay Karakose, Huseyin Pülat, Kazım Ozcelik, Huseyin Eken, Ali Duran, Adem Uslu

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