Thyroid Function Alteration in Obesity and the Effect of Bariatric Surgery.

The most common endocrine disease in obesity is hypothyroidism and secondary endocrine alterations, including abnormal thyroid function, are frequent in obesity. It is unclear whether impaired thyroid function is the cause or the consequence of increased adiposity; furthermore, there are no clear data regarding the best way to dose levothyroxine for patients with both hypothyroidism and obesity, and the effect of bariatric surgery (BS). The aim of the present article is to review some controversial aspects of the relation between obesity and the thyroid: (1) Thyroid function in obesity and the effect of BS (2) Thyroid hormone treatment (THT) in obese patients with hypothyroidism and the effect of BS. In summary: In morbidly obese patients, TSH is moderately increased. Morbid obesity has a mild central resistance to the thyroid hormone, reversible with weight loss. In morbidly obese hypothyroid patients, following weight loss, the levothyroxine dose/kg of ideal weight did not change, albeit there was an increment in the levothyroxine dose/kg of actual weight. From a clinical practice perspective, in morbid obesity, diagnosing mild hypothyroidism is difficult, BS improves the altered thyroid function and THT can be adapted better if it is based on ideal weight.

Evaluation of Thyroid Hormone Replacement Dosing in Morbidly Obese Hypothyroid Patients after Bariatric Surgery-Induced Weight Loss.

The most frequent endocrine disease in obese patients is hypothyroidism. To date, there are no clear data regarding what happens to the dose of levothyroxine (LT4) after bariatric surgery (BS). The objective of the present study was to evaluate thyroid hormone replacement dose in morbidly obese hypothyroid patients after BS-induced weight loss. We explore the best type of measured or estimated body weight for LT4 dosing. We performed an observational study evaluating patients with morbid obesity and hypothyroidism who underwent BS. We included 48 patients (three men). In morbidly obese hypothyroid patients 12 months after BS-induced weight loss, the total LT4 dose or the LT4 dose/kg ideal body weight did not change, while there was a significant increase in LT4 dose/body surface area, LT4 dose/kg weight, LT4 dose/kg adjusted body weight, LT4 dose/kg body fat, and LT4 dose/kg lean body weight. There were no differences in LT4 dose and its variation between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). The present study strongly suggests that LT4 dosing in obese hypothyroid patients can be individually adapted more precisely if it is based on ideal body weight.

Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation.

Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH-IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH-IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.

Central Resistance to Thyroid Hormones in Morbidly Obese Subjects Is Reversed after Bariatric Surgery-Induced Weight Loss.

Endocrine abnormalities are common in obesity, including altered thyroid function. The altered thyroid function of obesity may be due to a mild acquired resistance to the thyroid hormone. The aim of this study was to investigate the effect of weight loss after bariatric surgery (BS) on resistance to thyroid hormones in patients with extreme obesity compared with a control group. We performed an observational study evaluating patients with extreme obesity who underwent BS. We included 106 patients (83 women) and 38 controls (24 women). The primary endpoint was the thyrotroph thyroxine resistance index (TT4RI) and thyroid stimulating hormone (TSH) index (TSHRI). The parameters were studied before and after surgery. TSHRI and TT4RI were higher in the obese patients than in the control group. TT4RI and TSHI decreased significantly over time after surgery, with this decrease being associated with the excessive body mass index (BMI) loss and C-reactive protein (CRP). In extreme obesity, BS promotes a significant decrease in the increased TT4RI and TSHI. This decrease of TT4RI and TSHI is progressive over time after BS and significantly associated with excess BMI lost and CRP. Extreme obesity is characterized by a mild reversible central resistance to thyroid hormones.

Effect of Weight Loss after Bariatric Surgery on Thyroid-Stimulating Hormone Levels in Euthyroid Patients with Morbid Obesity.

Obesity is associated with several endocrine abnormalities, including thyroid dysfunction. The objective of this study was to investigate the effect of weight loss after bariatric surgery on thyroid-stimulating hormone (TSH) levels in euthyroid patients with morbid obesity. We performed an observational study, evaluating patients with morbid obesity submitted to bariatric surgery. We included 129 patients (92 women) and 31 controls (21 women). Clinical, anthropometric, biochemical, and hormonal parameters were evaluated. The primary endpoint was circulating TSH (µU/mL). Fasting TSH levels were higher in the obese group (3.3 ± 0.2) than in the control group (2.1 ± 0.2). The mean excessive body mass index (BMI) loss (EBMIL) 12 months after bariatric surgery was 72.7 ± 2.1%. TSH levels significantly decreased in the obese patients after surgery; 3.3 ± 0.2 vs. 2.1 ± 0.2 before and 12 months after surgery, respectively. Free thyroxine (T4) (ng/dL) levels significantly decreased in the obese patients after surgery; 1.47 ± 0.02 vs. 1.12 ± 0.02 before and 12 months after surgery, respectively. TSH decreased significantly over time, and the decrement was associated with the EBMIL. In euthyroid patients with morbid obesity, weight loss induced by bariatric surgery promotes a significant decline of the increased TSH levels. This decrement of TSH is progressive over time after surgery and significantly associated with excess BMI loss.

Oral glucose-stimulated growth hormone (GH) test in adult GH deficiency patients and controls: Potential utility of a novel test.

CONTEXT: The diagnosis of adult GH deficiency requires confirmation with a GH stimulation test. Oral glucose (OG) administration affects GH secretion, initially decreasing and subsequently stimulating GH secretion. OBJECTIVE: The aim of this study was to investigate the diagnostic efficacy and safety of a long OG test (LOGT) as a stimulus of GH secretion for the diagnosis of adult GH deficiency (AGHD). DESIGN: Prospective experimental cross-sectional study. SETTINGS: The study was conducted at the Endocrinology department of the University Hospital of a Coruña, Spain. PARTICIPANTS AND METHODS: We included 60 (40 women) AGHD patients (15) and controls (45) paired 1:3, of similar age, sex and BMI. The area under the curve (AUC) and peak were calculated for GH. The Mann-Whitney test was used to compare the different groups. ROC curve analyses were used. p-Values<0.05 were considered as statistically significant. INTERVENTIONS: The intervention consisted of orally administering 75g oral glucose administration; GH was obtained every 30min for a total of 300min. MAIN OUTCOME MEASUREMENT: Peak GH area under receiver operating characteristic curve (ROC-AUC) following LOGT. RESULTS: Peak GH (µg/L) levels were lower in the AGHD patients (0.26±0.09) than in the controls (4.00±0.45), p<0.001. After LOGT, with the ROC plot analysis the best peak GH cut-point was 1.0µg/L, with 100% sensitivity, 78% specificity, ROC-AUC of 0.9089 and 81.82% accuracy. There were no relevant adverse events during any of the LOGT. CONCLUSIONS: The LOGT could be a cheap, safe, convenient and effective test for the diagnosis of AGHD.

Circulating Levels of Irisin in Hypopituitary and Normal Subjects.

CONTEXT: The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP) is a situation characterized by decreased GH secretion and an altered body composition. OBJECTIVE: Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects. PARTICIPANTS AND METHODS: Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 µg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-ß were calculated. RESULTS: Fasting irisin levels (ng/ml) were similar in normal [208.42 (168.44-249.23)] and HP patients [195.13 (178.44-241.44)]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-ß, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-ß. CONCLUSIONS: We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH.