Biomedical subjects

J A Romijn

Publications and source records attributed to J A Romijn.

At least 19 recordsLinked to original sources

PubMed2007

Malignant paragangliomas associated with mutations in the succinate dehydrogenase D gene.

INTRODUCTION: Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene. AIM: The aim of the study was to report the different clinical expression patterns of malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution. RESULTS: Metastasis and/or local tumor invasion was documented 0 (n=2), 1, 18, and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n=2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone, and locally invasive paraganglioma of the bladder with lymph node metastases. Four of the five patients developed catecholamine excess during follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n=1), extra adrenal paraganglioma (n=2), and presumed subclinical disease (n=1). CONCLUSION: SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.

Adrenal Gland Neoplasms↗

PubMed2007

Mortality in patients treated for Cushing's disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma.

CONTEXT: Increased mortality in patients with pituitary tumors after surgical treatment has been reported. However, it is unknown to what extent excess mortality is caused by pituitary tumors and their treatment in general and to what extent by previous exposure to hormonal overproduction. OBJECTIVE: The aim of the study was to compare mortality between patients treated for Cushing's disease and nonfunctioning pituitary macroadenomas (NFMAs). DESIGN: This was a follow-up study. PATIENTS: We included 248 consecutive patients with pituitary adenomas treated by transsphenoidal surgery in our hospital for NFMAs (n = 174) and ACTH-producing adenomas (n = 74). The mean duration of follow-up after surgery was 10.1 +/- 7.2 yr for the whole cohort. OUTCOME MEASURES: The standardized mortality ratio (SMR) was calculated for the whole cohort and also for the two diseases separately. Cox regression analysis was used to compare mortality in patients with Cushing's disease with NFMA patients. RESULTS: Patients with Cushing's disease (39.1 +/- 16.1 yr) were significantly younger at time of operation than NFMA patients (55.3 +/- 13.4 yr). The SMR for the whole cohort was 1.41 [95% confidence interval (CI), 1.05-1.86]. The SMR in NFMA patients was 1.24 (95% CI, 0.85-1.74) vs. 2.39 (95% CI, 1.22-3.9) in patients with Cushing's disease. In patients with Cushing's disease, compared with NFMAs, the age-adjusted mortality was significantly increased: hazard ratio 2.35 (95% CI, 1.13-4.09, P = 0.008). CONCLUSIONS: Mortality in patients previously treated for Cushing's disease is increased, compared with patients treated for NFMAs. This implies that previous, transient overexposure to cortisol is associated with increased mortality.

Adenoma↗

PubMed2006

[Cushing's syndrome. II. New forms of treatment].

Several new therapeutic options both medicinal and surgical, have emerged for the treatment of Cushing's syndrome. In Cushing's disease caused by an adrenocorticotropin (ACTH) secreting pituitary adenoma, the introduction ofendoscopic pituitary surgery offers better visualization of the sella than does the traditional explorative surgery. However, at present it is unclear whether this will result in a better outcome. New drugs under investigation include universal somatostatin analogues such as SOM230, and a combination of a somatostatin analogue and dopamine agonist known as dopastatin. These agents may also be effective for the medicinal treatment of ectopic ACTH-secretion. Treatment with radioactive-labelled somatostatin-analogues such as 177lutetium octreotate is another option for these patients. The primary treatment for ACTH-independent Cushing's syndrome is laparoscopic adrenalectomy. In rare cases of bilateral adrenal hyperplasia, medicinal treatment aimed at new regulatory pathways of cortisol secretion can be applied.

ACTH-Secreting Pituitary Adenoma↗

PubMed2006

Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice.

AIMS/HYPOTHESIS: Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. MATERIALS AND METHODS: Chronic hepatic steatosis and hepatic insulin resistance were induced by high-fat feeding of male C57BL/6Jico mice for 6 weeks. In addition, acute hepatic steatosis in the absence of insulin resistance was induced by pharmacological blockade of beta-oxidation using tetradecylglycidic acid (TDGA). mTOR signalling was examined in liver homogenates. RESULTS: High-fat feeding caused obesity (p<0.001), hepatic steatosis (p<0.05) and hepatic insulin resistance (p<0.05). The phosphorylation of mTOR and its downstream targets p70S6 kinase and S6 ribosomal protein was two-fold higher in mice on a high-fat diet than in mice fed standard chow (all p<0.05) and associated with enhanced rates of protein synthesis. Acute induction of hepatic steatosis with TDGA had no effect on mTOR activity. The increased activity of the mTOR pathway in livers from mice on a high-fat diet could not be ascribed to diet-induced alterations in known modulators of mTOR activity such as circulating plasma leucine levels, phosphorylation of protein kinase B and AMP-activated protein kinase, and changes in mitochondrial function. CONCLUSIONS/INTERPRETATION: High-fat diet induces increase of the mTOR nutrient sensing pathway in association with hepatic insulin resistance, but not with hepatic lipid accumulation as such.

Animals↗

PubMed2006

Quality of life is decreased after treatment for nonfunctioning pituitary macroadenoma.

OBJECTIVE: Although a reduced quality of life (QoL) has been reported after long-term cure of functioning pituitary adenomas, the effect of successful treatment of nonfunctioning pituitary macroadenoma (NFMA) on QoL has not been fully addressed. Therefore, we evaluated a broad spectrum of QoL parameters in patients successfully treated for NFMA in our center. DESIGN: We conducted a case-control study. PATIENTS AND METHODS: We assessed QoL in 99 adult patients (mean age, 61.9 yr; range, 24-86 yr) in remission during long-term follow-up after surgical (n = 99) and additional radiotherapeutic (n = 37) treatment for NFMA by four validated health-related questionnaires (Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index, Nottingham Health Profile, and Short Form-36). Patient outcomes were compared with 125 controls and with age-adjusted reference values derived from the literature. RESULTS: NFMA patients reported significantly impaired QoL in all questionnaires compared with the 125 controls and the age-adjusted reference values. All subscales of fatigue, assessed using the Multidimensional Fatigue Index (general fatigue, physical fatigue, reduction in activity, reduction in motivation, and mental fatigue) were impaired. The scores in the Nottingham Health Profile pointed toward reduced energy and affected emotional reaction. In several subscales of the Short Form-36 (social functioning, role limitations due to physical problems, role limitations due to emotional problems, and general health perception), NFMA patients reported a reduced QoL. CONCLUSION: QoL is considerably reduced in patients after successful treatment of NFMA.

Adenoma↗

PubMed2006

[Acne vulgaris: endocrine aspects].

Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development of acne. The skin contains enzymes that convert precursor hormones to the more potent androgens such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be regulated locally. The effects of androgens on the skin are the result of circulating androgens and enzyme activity in local tissues and androgen receptors. Acne is a clinical manifestation of some endocrine diseases. The polycystic ovary syndrome has the highest prevalence. In women with acne that persists after puberty, in 10-200% of cases polycystic ovary syndrome is later diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the androgen-production (oestrogens) or by blocking the androgen receptor (cyproterone, spironolactone).

Acne Vulgaris↗

PubMed2006

A variable degree of intrauterine and postnatal growth retardation in a family with a missense mutation in the insulin-like growth factor I receptor.

CONTEXT: The type 1 IGF-I receptor (IGF1R) mediates the biological functions of IGF-I. Binding of IGF-I to the IGF1R results in autophosphorylation of the intracellular beta-subunit and activation of intracellular signaling. OBJECTIVE: The objective of this study was to evaluate the functional characteristics of a novel IGF1R mutation and describe the phenotypic features of two patients with this mutation. DESIGN: The study was performed in a university hospital. PATIENTS: We describe a 35-yr-old female with mild intrauterine growth failure, progressive postnatal growth retardation, severe failure to thrive, and microcephaly. Her daughter was born with severe intrauterine growth retardation and also showed postnatal failure to thrive and microcephaly. RESULTS: We found a heterozygous G3148-->A nucleotide substitution in the IGF1R gene, changing a negatively charged glutamic acid at position 1050 into a positively charged lysine residue (E1050K). E1050 is a conserved residue in the intracellular kinase domain. Dermal fibroblasts of the mother showed normal binding of iodinated IGF-I, but autophosphorylation and activation of downstream signaling cascades upon challenging with IGF-I was markedly reduced. Consequently, the maximal [(3)H]thymidine incorporation upon challenge with a dose range of IGF-I was reduced compared with a panel of control cells (3.65 +/- 1.79-fold vs. 6.75 +/- 4.7-fold stimulation; P < 0.01). These data suggest that the mutation results in the inactivation of one copy of the IGF1R gene. CONCLUSIONS: These two patients support the key role for IGF-I in intrauterine and postnatal growth. The different phenotypes of these and earlier described patients may be associated with variability in IGF-I signaling. The degree of intrauterine growth retardation may be partially determined by the presence or absence of maternal IGF-I resistance.

Adult↗

PubMed2006

Uncontrolled acromegaly is associated with progressive mitral valvular regurgitation.

INTRODUCTION: Recent cross-sectional studies have documented an association between acromegaly and regurgitant valvular heart disease. The aim of this study was to evaluate the change in prevalence of valvular heart disease in relation to the clinical activity, because the natural history of valvular changes in acromegaly is unknown. PATIENTS AND METHODS: Valvular regurgitation was assessed in 37 acromegalic patients (18 patients with active disease, and 19 with controlled disease) by conventional two-dimensional and Doppler echocardiography before and after an interval of 1.9 years (range 1.5-3.0 years). RESULTS: At baseline, valvular regurgitation (mitral and aortic sites combined) was present in 46% of the patients and increased to 67% at follow-up (P=0.008). Mitral regurgitation increased significantly from 32% to 60% (P=0.002), but no change was noted for the aortic valve (27% vs. 31%, NS). In patients with active disease, valvular regurgitation increased significantly from 56% at baseline to 88% at follow-up (P=0.031) due to a significant increase of mitral regurgitation from 39% to 78% at follow-up (P=0.016). In contrast, no increase in valvular regurgitation was found in patients with controlled disease. CONCLUSION: The prevalence of mitral, but not aortic, valvular regurgitation increased in patients with active acromegaly during follow-up. Patients with acromegaly require adequate cardiac evaluation and follow-up to establish the extent and progression of valvular involvement.

Acromegaly↗

PubMed2006

Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma.

OBJECTIVE: Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas (NFMA). In this study we evaluated the long-term effects of a treatment strategy in which postoperative radiotherapy was not routinely applied to patients with NFMA. DESIGN: This was a retrospective follow-up study. PATIENTS: We included 109 consecutive patients (age 56 +/- 13 yr) operated for NFMA between 1992 and 2004. RESULTS: Radiological imaging revealed a macroadenoma in all patients, with suprasellar extension in 96% and parasellar/infrasellar extension in 36% of cases. Visual field defects were present in 87% of the patients and improved in 84% of these patients after surgery. Only six patients received postoperative radiotherapy. Ten patients died during the follow-up period. Ninety-seven patients could be assessed for tumor regrowth or tumor recurrence after a mean follow-up period of 6.0 +/- 3.7 yr. In nine patients there was evidence for tumor regrowth, and in one patient tumor recurrence was observed. The mean time to tumor growth/recurrence after initial therapy was 6.9 (range 3-12) yr. Follow-up duration was found to be an independent predictor for tumor regrowth. CONCLUSION: Transsphenoidal surgery without postoperative radiotherapy is an effective and safe treatment strategy for NFMA, without evidence for tumor regrowth in 90% of all patients, at least for the duration of follow-up presented in this study. Additional studies are required to exclude higher regrowth and recurrence rates during prolongation of the duration of follow-up.

Adenoma↗

PubMed2006

Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice.

AIMS/HYPOTHESIS: This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin, we also determined the metabolic effects of growth hormone releasing peptide 6 (GHRP-6), a specific GHS receptor agonist. In addition, we explored the biological significance of des-ghrelin (unacylated ghrelin) in this experimental context. MATERIALS AND METHODS: Vehicle (n=8), ghrelin (n=9), GHRP-6 (n=9), des-ghrelin (n=8) or a combination of des-ghrelin and ghrelin (n=7) were infused i.v. for 3 h. Simultaneously, endogenous glucose production and glucose disposal were measured by (14)C-glucose dilution during a hyperinsulinaemic-euglycaemic clamp. Tissue-specific glucose uptake in muscle and adipose tissue was measured using (3)H-2-deoxyglucose. RESULTS: During hyperinsulinaemia, glucose disposal was 31% higher in mice treated with ghrelin than in those treated with vehicle (77+/-16 and 59+/-8 micromol kg(-1) h(-1), respectively, p<0.05). This was in accordance with enhanced 2-deoxyglucose uptake in muscle in ghrelin-treated animals. In contrast, endogenous glucose production was less effectively suppressed by insulin during ghrelin infusion (46+/-22 vs 71+/-11% in controls, p<0.05). GHRP-6 did not affect insulin action. Des-ghrelin hampered insulin's capacity to inhibit endogenous glucose production, whereas it did not affect glucose disposal. The restraining effects of des-ghrelin and ghrelin on hepatic insulin action were abolished by simultaneous administration of both peptides. CONCLUSIONS/INTERPRETATION: Ghrelin hampers insulin's capacity to suppress endogenous glucose production, whereas it reinforces the action of insulin on glucose disposal, independently of food intake and body weight. These metabolic effects are unlikely to be mediated by the GHS receptor. Furthermore, simultaneous administration of des-ghrelin abolishes the inhibitory effect of ghrelin on hepatic insulin action.

Animals↗

PubMed2006

Preterm birth and later insulin resistance: effects of birth weight and postnatal growth in a population based longitudinal study from birth into adult life.

AIMS/HYPOTHESIS: An increased risk of type 2 diabetes mellitus is associated with low birthweight after full-term gestation, including amplification of this risk by weight gain during infancy and adult body composition. Premature birth is also associated with insulin resistance, but studies conducted so far have not provided follow-up into adulthood. We studied the effects of (1) lower birthweight (as standard deviation score [SDS]) and infancy weight gain on insulin resistance in 19-year-olds born before 32 weeks of gestation, and (2) the interaction between lower birthweight SDS and infancy weight gain, as well as between lower birthweight and adult body composition, on insulin resistance. METHODS: This was a prospective follow-up study in 346 subjects from the Project on Preterm and Small-for-gestational-age infants cohort, in whom fasting glucose, insulin and C-peptide levels were measured at 19 years. Insulin resistance was calculated with homeostatic modelling (homeostatic model assessment for insulin resistance index [HOMA-IR]). RESULTS: Birthweight SDS was unrelated to the outcomes. Rapid infancy weight gain until 3 months post-term was weakly associated with higher insulin level (p=0.05). Adult fatness was positively associated with insulin and C-peptide levels and HOMA-IR (all p<0.001). On these parameters, there was a statistical interaction between birthweight SDS and adult fat mass (p=0.002 to 0.03). CONCLUSIONS/INTERPRETATION: In subjects born very preterm, rapid infancy weight gain until 3 months predicted higher insulin levels at 19 years, but the association was weak. Adult obesity strongly predicted higher insulin and C-peptide levels as well as HOMA-IR. The effect of adult fat mass on these parameters was dependent on its interaction with birthweight SDS.

Adult↗

PubMed2006

Mitochondrial diabetes and its lessons for common Type 2 diabetes.

Multiple pathogenic pathways are able to deregulate glucose homoeostasis leading to diabetes. The 3243A>G mutation in the mtDNA (mitochondrial DNA)-encoded tRNALeu,UUR gene was found by us to be associated with a particular diabetic subtype, designated MIDD (maternally inherited diabetes and deafness). This mutation causes an imbalance in the mitochondrion between proteins encoded by the nuclear and mitochondrial genomes, resulting in a gradual deterioration of glucose homoeostasis during life. Remarkably, carriers of the 3243A>G mutation are generally not obese. The mutation also results in enhanced radical production by mitochondria. We propose that this mutation leads to the development of diabetes due to an inappropriate storage of triacylglycerols within adipocytes. The result is a fatty acid-induced deterioration of pancreatic beta-cell function. In combination with an enhanced radical production in the beta-cell due to the mutation, this leads to an age-dependent, accelerated decline in insulin production. In common Type 2 (non-insulin-dependent) diabetes, which is generally associated with obesity, a decline in mitochondrial function in adipose cells seems to result in an inappropriate scavenging of fatty acids by beta-oxidation. As a consequence, a systemic overload with fatty acids occurs, leading to an enhanced decline in beta-cell function due to lipotoxicity.

DNA, Mitochondrial↗

PubMed2006

The effects of thyrotropin-suppressive therapy on bone metabolism in patients with well-differentiated thyroid carcinoma.

Patients with differentiated thyroid carcinoma (DTC) are commonly treated long-term with thyrotropin (TSH)- suppressive thyroxine replacement therapy resolving in a state of subclinical hyperthyroidism. The relationship between subclinical hyperthyroidism and osteoporosis is not clear. In this review, we systematically selected and analyzed 21 studies addressing this issue. Although multiple methodological differences between studies prevented a structured meta-analysis, our data suggest that postmenopausal women with subclinical hyperthyroidism are most at risk, whereas no increased risk was observed in men and premenopausal women. Based on these findings we believe that measurement of bone mineral density is recommended in postmenopausal women with DTC starting TSH suppressive therapy. This should be subsequently regularly measured to enable timely intervention with bone protective agents.

Adult↗

PubMed2006

Quality of life in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomized controlled trial.

OBJECTIVE: The impact of prolonged subclinical hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH-suppressive thyroxine therapy as a model for subclinical hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life. DESIGN: We performed a prospective, single-blinded, placebo-controlled, randomized trial of 6 months' duration with two parallel groups. PATIENTS AND METHODS: Twenty-four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with L-thyroxine completed the study. L-thyroxine dose was replaced by study medication containing L-thyroxine or L-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires. RESULTS: At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low-TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low-TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index-20, P = 0.003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form-36; P = 0.050) was observed. No improvement in the SDQ score was observed. CONCLUSION: In summary, quality of life in patients with DTC and long-term subclinical hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.

Fatigue↗

PubMed2006

A bioluminescence assay for thyrotropin receptor antibodies predicts serum thyroid hormone levels in patients with de novo Graves' disease.

BACKGROUND: TSH receptor antibodies (TBII) in Graves' disease (GD) may be TSH receptor stimulating (TSAb) and blocking (TBAb) antibodies. In commercially available assays however, only total TBII titres can be measured, without discriminating between TSAb and TBAb. OBJECTIVE: To design a TBII bioassay to detect of TSAb and to correlate TSAb activity with severity of hyperthyroidism in de novo GD patients. PATIENTS: Thirty-five patients with de novo GD and 27 controls. METHODS: The JP-26-26 cell line, which constitutively expresses the TSH receptor (TSHR), was stably transfected with a cyclic adenosine monophosphate responsive element--luciferase construct. The clone B1 exhibited a near linear increase in luminescence from 0.2 mU/l to 50 mU/l bovine TSH and was used as a TBII bioassay. TBII, free T4 and TSH were measured in the sera of all patients and controls. RESULTS: In the sera of 35 GD patients, TBII titres did not correlate with serum free T4 concentrations. In contrast, a strong and highly significant correlation was found between TSHR stimulating activity (luminescence) as measured with the TBII bioassay and serum free T4 levels (R = 0.80, P < 0.001). Interestingly, the luminescence/TBII ratio had a wide range at low TBII titres, whereas high TBII titres were associated with a low degree of TSHR activation. The TBII bioassay also detected TBAb in GD patients who spontaneously developed hypothyroidism. CONCLUSIONS: The B1-TBII-bioassay as developed in our laboratory has a high sensitivity for the detection of TSAb in GD and predicts the severity of hyperthyroidism in untreated GD patients. In addition, we found that high TBII titres are associated with weak TSHR activation.

Adult↗

PubMed2006

Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies.

OBJECTIVE: Lithium has been reported to increase radioactive iodine (RaI) doses in benign thyroid disease and in differentiated thyroid carcinoma (DTC). It is not known whether lithium influences the outcome of RaI therapy in DTC. We therefore studied the clinical effects of RaI without and with lithium carbonate in patients with proven metastatic DTC. Controversy also exists on the mechanism by which lithium increases RaI dose in DTC. We performed an in vitro study specifically aimed at examining the effects of lithium on the sodium iodide symporter (NIS). DESIGN: In a clinical study, 12 patients were selected with metastases of DTC who had received previous RaI therapy without lithium (control) that had not influenced tumour progression, despite RaI accumulation in metastases. The patients received 1200 mg lithium carbonate/day followed by 6000 MBq RaI. Outcome parameters were RaI uptake, serum thyroglobulin (Tg) levels and radiological dimensions of metastases compared between RaI with lithium and control. In an in vitro study, iodide uptake was studied in the benign rat thyroid cell line FRTL-5, in the polarized non-thyroid MDCK cell line, stably transfected with human sodium iodide symporter (hNIS) to study the effects of lithium on NIS in a non-thyroid background, and the human follicular thyroid carcinoma cell line FTC133-hNIS to study lithium effects in a background of DTC. Lithium chloride (LiCl) was added in concentrations up to 2 mM for 0-48 h. Both steady-state iodide uptake (30 min) and initial rate (2 min) were studied using a specific activity of 100 mCi/mmol I, the latter experiment to determine lithium effects on substrate dependency. Iodide efflux studies were performed as well. RESULTS: Despite an increased uptake of RaI in seven patients, no beneficial effect of RaI with lithium was observed on the clinical course as assessed by serum Tg measurements and radiographically. In the in vitro studies, no effects of LiCl on iodide uptake or efflux were observed. CONCLUSIONS: The addition of lithium to RaI did not have any beneficial effects on the clinical course in 12 patients with metastatic DTC. No beneficial effects of lithium on iodide uptake were observed in vitro. Therefore, the clinical value of lithium in DTC remains subject to debate.

Adjuvants, Pharmaceutic↗

PubMed2006

Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomised controlled trial.

OBJECTIVE: The impact of prolonged subclinical hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for subclinical hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism. DESIGN: We performed a prospective, single-blinded, placebo-controlled, randomised trial of 6 months duration with 2 parallel groups. PATIENTS: Twenty-five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with l-thyroxine completed the study. l-thyroxine dose was replaced by study medication containing l-thyroxine or l-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients). MEASUREMENTS: We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones. RESULTS: At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values. CONCLUSION: In summary, glucose and lipid metabolism in patients with DTC and long-term subclinical hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.

Adult↗

PubMed2006

Gut-brain axis: regulation of glucose metabolism.

Obesity and type II diabetes mellitus have reached epidemic proportions. From this perspective, knowledge about the regulation of satiety and food intake is more important than ever. The gut releases several peptides upon feeding, which affect hypothalamic pathways involved in the regulation of satiety and metabolism. Within the hypothalamus, there are complex interactions between many nuclei of which the arcuate nucleus is considered as one of the most important hypothalamic centres that regulates food intake. The neuropeptides, which are present in the hypothalamus and are involved in regulating food intake, also play a key role in regulating glucose metabolism and energy expenditure. In synchrony with the effects of those neuropeptides, gastrointestinal hormones also affect glucose metabolism and energy expenditure. In this review, the effects of the gastrointestinal hormones ghrelin, cholecystokinin, peptide YY, glucagon-like peptide, oxyntomodulin and gastric inhibitory polypeptide on glucose and energy metabolism are reviewed. These gut hormones affect glucose metabolism at different levels: by altering food intake and body weight, and thereby insulin sensitivity; by affecting gastric delay and gut motility, and thereby meal-related fluctuations in glucose levels; by affecting insulin secretion, and thereby plasma glucose levels, and by affecting tissue specific insulin sensitivity of glucose metabolism. These observations point to the notion of a major role of the gut-brain axis in the integrative physiology of whole body fuel metabolism.

Appetite Regulation↗