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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

INTRODUCTION Thyroid peroxidase activity inhibiting immunoglobulins (anti-TPO Ab) is a sign of autoimmune process in the thyroid gland. Association of hyperthyroidism and diabetes mellitus has been classically described. However, hypometabolic state, as a consequence of hypothyroidism, is not frequently linked with the biological activity of insulin. CASE DESCRIPTION A 51-year old man was admitted to the Clinic with unregulated diabetes, untreated for 5 yrs. Insulin therapy was introduced one year before, with 96 units on admission. He had bowel movements every three days. BH 176cm, BW 120kg, a puffy face and swollen body. Fundus examination did not show specific diabetic leasions. Hepatic steatosis was present on ultrasound examination. Occlusion of coronary arteries and superficial femoral artreries was present on angiography, and stenosis of carotid artreies on doppler duplex examination. HbA1c 14.7%. TSH 85.7 mlU/l, FT4 1.6 pmol/l, FT3 1.4. Anti TPO Ab >600 IU/ml, triglycerides 2.26 mmol/l, HDL 1.15, cholesterolemia 10.0. Levothyroxine substitution was introduced starting with 25 mgr, gradually increasing up to 75 mgr. The need for insulin gradually decreased and finally it was switched to glibenclamide 5mg +0+2.5 mg. On discharge his FBG was 7.0 mmol/l. HOMA -B 52.3, HOMA-R 9.8. DISCUSSION We can conclude that in our patient secondary obesity caused deterioration of diabetes. After introduction of substitution therapy with levothyroxine, decrease of insulin resistance and of cholesterol level was established. The duration of undiagnosed hypothyroidism can be a matter of speculation. However, the beneficial effect of normalized metabolism on atherosclerotic process will be obvious in the future.
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PMID:[Hashimoto's hypothyroidism associated with insulin resistance in type 2 diabetes]. 1706 92

Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia.
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PMID:Hormone replacement therapy and vascular risk disorders in adult hypopituitarism. 1728 80

Acanthosis nigricans (AN) develops commonly in obese adults, yet its prevalence and metabolic significance in children and adolescents have not been determined. To address these issues, 100 obese children and adolescents enrolled in the obesity clinic at the Royal Hospital, Muscat, Oman, were chosen at random and examined. AN was observed in 43 of the study children (43%). The frequency and severity of AN increases and significantly with increasing body mass index (BMI) in these children. Twenty patients with obesity and AN and 20 age-matched nonacanthotic obese children, randomly selected from the study children, were investigated. Their oral glucose tolerance and serum C-peptide responses to IV glucagon were evaluated. Circulating concentrations of free thyroxine (FT4), TSH, basal and ACTH-stimulated cortisol, testosterone, leutinizing hormone, (LH), follicle-stimulating hormone (FSH), and prolactin were measured by radioimmunoassay (RIA). Children with AN exhibited higher basal and glucagon-stimulated C-peptide concentrations than the nonacanthotic obese group. Two hours after the oral load of glucose (1.75 g/kg), serum glucose concentration (6.3 +/- 1.4 mmol/L) was higher in the acanthotic group versus the nonacanthotic group (5.2 +/- 0.8 mmol/L). Impaired glucose tolerance was detected in two children with AN (10%), and in none of the nonacanthotic controls. Hypothyroidism was diagnosed in two (10%) children with AN (TSH = 109 and 18 mIU/mL and FT4 = 4.6 and 13.5 pmol/L respectively), while all the nonacanthotic children were euthyroid. Serum testosterone concentration was insignificantly lower in the acanthotic group (6.5 +/- 3.9 ng/dL) versus the nonacanthotic children (8.3 +/- 4.5 ng/dL). Basal serum LH, FSH and prolactin concentrations and basal and ACTH-stimulated cortisol levels did not differ between the two study groups. Plasma triglyceride concentration was significantly higher in the acanthotic group (1.43 +/- 0.5 mmol/L) versus the nonacanthotic group (1.05 +/- 0.45 mmol/L), and was correlated significantly with BMI (r = 0.446, P < 0.05). In conclusion, obesity is a significant risk factor for the development of AN in children. AN is a reliable skin marker of hyperinsulinemia in obese children and adolescents. The prevalence of impaired glucose tolerance (10%) and primary hypothyroidism (10%) appears to be higher in obese acanthotic children than in those without AN.
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PMID:Prevalence and significance of Acanthosis nigricans in children and adolescents. 1737 96

Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by Albright's hereditary osteodistrophy (AHO) and resistance to hormones that act via the alpha subunit of the Gs protein (Gsalpha) protein, ie PTH, TSH, FSH/LH, and, as recently described in limited series, GHRH. However, the current lack of data on GHRH secretion, obesity and short stature included in the AHO phenotype hampers interpretation of GH secretory status and its effects on these subjects. We evaluated GH secretion after GHRH plus arginine (Arg) stimulus, IGF-I levels and anthropometric features in an exclusively pediatric population of 10 PHP-Ia subjects. Of our PHP-Ia children, 5 out of 10 (50%) showed impaired GH responsiveness to the provocative test, with a lower prevalence than the 75-100% previously reported. A negative correlation (p=0.024) was found between GH secretion and body mass index (BMI), whereas no correlation emerged between GH and IGF-I values (p=0.948). Height and growth velocity did not significantly differ between GH-deficient and GH-sufficient subjects. In the 5 GH-deficient patients, GHRH resistance could arguably be responsible for hormonal impairment; however, 3 of them were obese, showing normal stature and IGF-I levels: the increased BMI in these subjects could influence GH secretion and its effects. In conclusion, GH deficiency is frequent among PHP-Ia children and its prevalence is variable, two factors indicating that GH secretory testing should be part of the routine management of this patient group. It could be argued that GHRH resistance is the pathogenetic mechanism in most patients, but further studies on GHRH secretion are needed to define which values can be considered as raised. Lastly, because BMI has been indicated as a major determinant of evoked adult GH response to provocative testing, GH levels related to increased BMI also in childhood could be helpful in defining GH assessment in obese or overweight PHP-Ia children.
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PMID:GH secretion in a cohort of children with pseudohypoparathyroidism type Ia. 1739 98

Obesity and metabolic syndrome are increasing dramatically worldwide, contributing to cardiovascular morbidity and mortality. There are currently few safe and efficacious therapeutics for obesity and most strategies are focused on appetite suppression. Thyroid hormones reduce adiposity via increased metabolic rate, but unfortunately they cause large changes in metabolic rate and direct cardiac acceleration, making them useless for treating obesity. Thyroid hormone receptors (TRs) work as transcription factors and two subtypes exist: TRalpha and TRbeta. TRalpha mediates tachycardia and much of the metabolic rate effect, while TRbeta mediates cholesterol and TSH lowering effects of thyroid hormones. TRbeta activation modestly increases metabolic rate such that a therapeutic window of 5-10 fold increases in metabolic rate can be seen without tachycardia. This was initially studied in TRalpha(1)(-/-) mice. Recent structure activity work has resulted in the discovery of several TRbeta selective thyromimetics such as KB-141. Studies with KB-141 show that it has a 10-fold window in which therapeutic increases in metabolic rate are seen without tachycardia or cardiac hypertrophy. This agent lowers cholesterol in rats and primates. In primates, KB-141 causes significant weight and cholesterol reduction in addition to the independent risk factor Lp(a). These effects were seen without any effect on heart rate, unlike thyroid hormone (T(3)). Further work with TRbeta selective agents is warranted and recent work suggests the possibility of developing compounds that selectively penetrate different tissues which may have an even more desirable therapeutic window. Selective thyromimetics, therefore, may be useful as adjunctive therapy to appetite suppressants along with exercise and diet restriction.
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PMID:Therapeutic potential for thyroid hormone receptor-beta selective agonists for treating obesity, hyperlipidemia and diabetes. 1743 Feb 19

The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic-pituitary-thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P<0.0001 for all). Serum total thyroxine (TT(4)), tri-iodothyronine, free T(4) (FT(4)) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT(4) fraction (FFT(4)) was calculated. Serum thyrotropin (TSH) concentrations were measured in nine animals by validating a heterologous canine TSH assay with recombinant feline TSH as a standard. FT(4), FFT(4), NEFAs, and leptin were significantly higher in obese cats. FT(4) had the strongest positive correlation with obesity indices BF, BMI, girth, NEFA, and leptin. Fatty acids oleate and palmitate were shown to inhibit T(4) binding to pooled cat serum in vitro, suggesting the possibility that this mechanism was also relevant in vivo. Serum TT(4) and TSH did not rise significantly. The implications for thyroid hormone (TH) action are not yet clear, but fatty acids have been proposed to inhibit the cellular uptake of TH and/or pituitary TH receptor binding, leading to TH resistance. Increased leptin may also alter sensitivity to negative feedback of TH. In conclusion, feline obesity is associated with a significant increase in FT(4) within the normal range; future investigation into the cellular thyroid status will be necessary to establish cause and effect in this obesity model.
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PMID:Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats. 1764 Dec 76

Case study of a young female patient with severe hypothyroidism due to autoimmune thyroiditis and multiple ovarian cysts is reported. A 14-year 7-month-old girl presented with pelvic and abdominal pain and severe asthenia. Her last menstrual period was 10 months before presentation. Physical examination showed obesity; apathetic and flat expression; periorbital puffiness; pale, cold, dry skin and slow sustained reflexes; swelling in the hands and feet; no galactorrhea; a hardly palpable thyroid gland; and ovaries with a palpable irregular surface. Her heart rate was 90 bpm with a blood pressure within the normal range (110/70 mmHg). Laboratory findings showed severe hypothyroidism (thyroid-stimulating hormone [TSH]: 960 mIU/L), gravis macrocytic anemia, hyperfibrinogenemia, and hyperprolactinemia. Imaging examinations revealed a normal-size thyroid with irregular echogenicity, strongly hypoechogenous area at the neck ultrasonography, bilateral multilocular ovarian masses with cystic components at pelvic ultrasound and computed tomography, and both anterior and posterior pericardial effusion at echocardiography. As soon as thyroid replacement therapy was initiated, all symptoms progressively disappeared and biochemical and hormonal values normalized, while the right ovary did not decrease in size during the follow-up period. For this reason, our patient underwent right ovarian wedge resection 14 months after the initiation of medication replacement. Ovarian histological examination showed a benign ovarian cyst with extensive hemorrhage and myxedematous infiltration. It is concluded that it is important to recognize early in young girls the association between large multiple ovarian cysts and high elevated levels of TSH in order to resolve this disorder with substitutive therapy.
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PMID:Multiple ovarian cysts in a young girl with severe hypothyroidism. 1802 Sep 17

Noninsulindependent diabetes mellitus is 2-4 times more prevalent in Turner subjects as compared to normal females, and tends to develop at a younger age, but it is usually mild and responsive to weight loss or monotherapy. The primary pathogenic event is beta cell dysfunction, but insulin resistance also plays a central role and is worsened by the presence of hypertension, obesity and dyslipidemia which are common in Turner syndrome. We present the case of a 30 year-old female patient with short stature, 141cm (<-- 2.5 SD), overweight 51kg, waist circumference 79cm, triangular facies, downslanting palpebral fissures, low set ears, short neck, secondary amenorrhea, palpitations, a history of polyuria, polydypsia of three months duration and a fasting morning glucose of 260 mg/dL. Cardiac and renal defects were excluded, hormonologic evaluation was consistent with hypergonadotropic hypogonadism (FSH 65 mUI/mL) and primary hypothyroidism (TSH 5.68 microUI/mL) and karyotype was 45,XO. She also had hypercholesterolemia (247 mg/dL), hypocalcemia (8 mg/dL), mild elevation of hepatic enzymes (ALAT 51 U/L) and osteopenia (Tscore--2.22). Glycaemic control was achieved with diet only; therapy consisted of hormone replacement theraphy, thyroxine and beta blockers.
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PMID:Diabetes mellitus and Turner syndrome. 1833 65

Overt hypothyroidism is associated with an increased prevalence of cardiovascular heart disease (CHD). The role of subclinical hypothyroidism as risk factor for cardiovascular diseases is supported by recent meta-analysis. However it still remains to be established whether hypothyroidism favors atherosclerosis independently of its effects on cardiovascular risk factors, such as hypercholesterolemia or hypertension. To assess whether hypothyroidism might be a risk factor per se, we analyzed carotid lesions assessed by US examination in two large populations with similar risk factors and displaying hypo- or euthyroidism. We selected, among a population of patients referred for assessment of hyperlipidemia, 794 hypothyroid patients (TSH>4mU/L), and 1588 euthyroid patients matched for the main cardiovascular risk factors (age, gender, lipid levels, hypertension, diabetes, smoking habits and obesity). All the patients had evaluation of their arterial carotid plaques, and about half of them had measurement of carotid intima-media thickness (IMT). Our hypothyroid population included 90% of patients with normal FT4 levels (subclinical hypothyroidism). We found that neither prevalence nor severity of carotid plaques nor carotid IMT were significantly different between hypothyroid patients and controls. To assess whether thyroid hormones may predict carotid atherosclerosis, we performed multivariate regression analyses, and we showed that, in both populations of hypothyroid and euthyroid patients, neither the TSH values nor the FT4 concentrations were independent risk factors for carotid atherosclerosis. In conclusion, we showed that, among a population of hyperlipidemic patients, hypothyroidism is not associated with an increased risk for carotid atherosclerosis when cardiovascular risk factors are accounted for.
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PMID:Hypothyroidism is not associated with increased carotid atherosclerosis when cardiovascular risk factors are accounted for in hyperlipidemic patients. 1864 81

Several population-based studies have shown a significant association between TSH-level and BMI (body mass index). About 30% of the rest energy expenditure are regulated by thyroid hormones, which generated the hypothesis that thyroid hormone substitution with TSH-titration into the lower reference levels may prevent body weight gain. The opposite effect of thyroid hormones is appetite stimulation, which may be responsible for body weight gain in case of substitutive medication. The association between TSH and BMI has become a complex topic in the light of the endocrine activity of adipocytes. Adipocytes are not a silent fat mass, but increase the hormone level of leptin, which influences neurones in the hypothalamus, the thyreotropic axis and TSH secretion. BMI is positively correlated with serum leptin. Elevated leptin levels, endogenous in individuals with high BMI or exogenous after leptin injection for treatment of hypothalamic amenorrhoea, shift TSH in the upper reference level. Borderline elevated TSH levels are reversible in case of body weight reduction in obese persons. It remains unclear whether high TSH levels or high leptin level are responsible for obesity or represent secondary phenomenon. Recommendation for daily practice: Borderline elevated TSH-levels in obese patients will decrease in case of body weight reduction without hormone medication. After definitive treatment of hyperthyroidism patient's history for use of carbohydrates (increased during hyperthyroidism) should be noticed and substitution with thyroid hormones aims at TSH in the lower reference level. As body weight gain is observed in all TSH groups, a special concept for prevention and therapy of obesity (diet, daily exercise, behaviour training) should be initiated early and additionally to medication.
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PMID:[Obesity, energy regulation and thyroid function: is borderline elevated TSH-level the cause or secondary phenomenon of obesity]. 1885 23


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