Biomedical subjects

Eric Fliers

Publications and source records attributed to Eric Fliers.

At least 19 recordsLinked to original sources

PubMed2006

"Diabetes of the elderly" and type 2 diabetes in younger patients: possible role of the biological clock.

The increased prevalence of type 2 diabetes in the aged has been recognized for a long time. Within the last decades, a growing number of younger subjects and even children are prone to develop type 2 diabetes. In both groups, aged and young, the biological clock, located in the suprachiasmatic nucleus of the hypothalamus (SCN) is malfunctioning as evidenced by disturbed sleep cycles and altered circadian rhythms. While elderly patients have an impaired function of the SCN due to the degeneration of neurons, we propose that in younger subjects the clock loses its "feeling" for internal and external rhythms caused by the modern lifestyle. Sleeping late and less coupled with constant metabolic excess alter both internal and external environmental stimuli to the brain. In response to these alterations, the rhythm of the biological clock is disrupted which may lead to the metabolic syndrome and type 2 diabetes.

Adult↗

PubMed2006

Prediction of treatment response by HPA-axis and glucocorticoid receptor polymorphisms in major depression.

OBJECTIVE: We investigated whether treatment response is predicted by hypothalamus-pituitary-adrenal (HPA) axis parameters, or by genetic polymorphisms in the glucocorticoid receptor (GR), that regulates its feedback. METHODS: Ninety-eight outpatients completed 8 weeks of paroxetine treatment. Treatment response was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD) ratings. At baseline, 24h urinary cortisol excretion, and cortisol and ACTH concentrations in a DEX/CRH test were measured. The presence of polymorphisms in the GR DNA sequence (BclI, ER22/23EK, N363S) was determined. Prediction of treatment response was analysed by calculating response rates per tertile of an HPA-axis parameter and per GR genotype. RESULTS: The response rate in the high ACTH tertile was significantly lower as compared to the intermediate tertile, but not compared to the low tertile (response rates from high to low tertile: 33%, 67% and 42%). Carriers of the BclI polymorphism had higher ACTH values than non-carriers (baseline ACTH: 3 versus 5ng/l, p=0.02) and showed a trend towards lower decrease of HRSD rates than non-carriers (HRSD decrease: 8 versus 11, respectively, p=0.07). In a subgroup of BclI carriers, patients in the high ACTH tertile had a lower decrease in HRSD and lower response rates than patients in the low ACTH tertiles (HRSD decrease from high to low tertile: 5, 9 and 11, p<0.01). CONCLUSION: The results suggest that hyperactivity of the HPA-axis predict worse treatment outcome. The BclI polymorphism explains, in part, DEX/CRH test results and tends to be associated with worse treatment outcome.

Adolescent↗

PubMed2006

Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes.

BACKGROUND: Kallmann's syndrome (KS) is a clinically and genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Mutations in KAL1 causing the X-linked form of KS have been identified in 10% of all KS patients and consistently result in a severe reproductive phenotype. KAL1 gene encodes for anosmin-1, a key protein involved in olfactory and GnRH neuronal migration through a putative interaction with FGFR1. Heterozygous mutations in the FGFR1 gene accompanied by a high frequency of cleft palate and other facial dysmorphisms were recently identified in 8% of a large KS cohort, yet the reproductive phenotype of KS patients harboring FGFR1 mutations has not been described. RESULTS: One hundred and fifty probands with KS (130 males and 20 females) were studied to determine the frequency and distribution of FGFR1 mutations and their detailed reproductive phenotypes. Fifteen heterozygous mutations in unrelated probands were identified. Twelve missense mutations (p.R78C, p.V102I, p.D224H, p.G237D, p.R254Q, p.V273M, p.E274G, p.Y339C, p.S346C, p.I538V, p.G703S and p.G703R) were distributed among the first, second and third immunoglobulin-like domains (D1-D3), as well as the tyrosine kinase domain (TKD). The mutations Y339C and S346C are located in exon 8B and code for the isoform FGFR1c. Additionally, two nonsense mutations (p.T585X and p.R622X) were documented in the TKD of the protein. A wide spectrum of reproductive function was observed among KS probands including: (1) a severe phenotype demonstrated by microphallus, cryptorchidism, no pubertal development, undetectable serum gonadotropins and low serum testosterone (T) and inhibin B; (2) partial pubertal development; (3) the fertile eunuch variant of IHH with normal testicular size and active spermatogenesis with a reversal of HH after T therapy. In addition, we found an even wider spectrum of reproductive function within pedigrees carrying an FGFR1 mutation ranging from IHH to delayed puberty to normal reproductive function (anosmia only or asymptomatic carriers). These observations strongly suggest a role for other genes that modify the phenotype of FGFR1 mutations. CONCLUSION: KS patients and family members carrying an FGFR1 mutation present a broad spectrum of pubertal development in contrast to the almost uniform severe clinical phenotype described in KS subjects with a KAL1 mutation. Additionally, this report implicates the isoform FGFR1c in the pathogenesis of KS.

Adolescent↗

PubMed2006

Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland.

A major change in thyroid setpoint regulation occurs in various clinical conditions such as critical illness and psychiatric disorders. As a first step towards identifying determinants of these setpoint changes, we have studied the distribution and expression of thyroid hormone receptor (TR) isoforms, type 2 and type 3 deiodinase (D2 and D3), and the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the human hypothalamus and anterior pituitary. Although the post-mortem specimens used for these studies originated from patients who had died from many different pathologies, the anatomical distribution of these proteins was similar in all patients. D2 enzyme activity was detectable in the infundibular nucleus/median eminence (IFN/ME) region coinciding with local D2 immunoreactivity in glial cells. Additional D2 immunostaining was present in tanycytes lining the third ventricle. Thyrotropin-releasing hormone (TRH) containing neurons in the paraventricular nucleus (PVN) expressed MCT8, TRs as well as D3. These findings suggest that the prohormone thyroxine (T4) is taken up in hypothalamic glial cells that convert T4 into the biologically active triiodothyronine (T3) via the enzyme D2, and that T3 is subsequently transported to TRH producing neurons in the PVN. In these neurons, T3 may either bind to TRs or be metabolized into inactive iodothyronines by D3. By inference, local changes in thyroid hormone metabolism resulting from altered hypothalamic deiodinase or MCT8 expression may underlie the decrease in TRH mRNA reported earlier in the PVN of patients with critical illness and depression. In the anterior pituitary, D2 and MCT8 immunoreactivity occurred exclusively in folliculostellate (FS) cells. Both TR and D3 immunoreactivity was observed in gonadotropes and to a lesser extent in thyrotropes and other hormone producing cell types. Based upon these neuroanatomical findings, we propose a novel model for central thyroid hormone feedback in humans, with a pivotal role for hypothalamic glial cells and pituitary FS cells in processing and activation of T4. Production and action of T3 appear to occur in separate cell types of the human hypothalamus and anterior pituitary.

Critical Illness↗

PubMed2006

Changes within the thyroid axis during critical illness.

Pronounced alterations in plasma thyroid stimulating hormone and thyroid hormone levels occur during critical illness without any evidence for thyroid disease. Plasma T3 decreases and plasma rT3 increases within a few hours after the onset of disease, and the magnitude of these changes is related to the severity and the duration of the disease. This article reviews the mechanisms behind the observed changes, and focuses on the regulation of thyroid hormone deiodination and transport, as well as the potential positive or negative effects for both the acute and the chronic phase of critical illness.

Acute Disease↗

PubMed2006

Hypothalamic thyroid hormone feedback in health and disease.

The role of the human hypothalamus in the neuroendocrine response to illness has only recently begun to be explored. Extensive changes in the hypothalamus-pituitary-thyroid (HPT) axis occur within the framework of critical illness. The best-documented change in the HPT axis is a decrease in serum concentrations of the biologically active thyroid hormone triiodothyronine (T3). From studies in post-mortem human hypothalamus it appeared that low serum T3 and thyrotropin (TSH) during illness (nonthyroidal illness, NTI) are paralleled by decreased thyrotropin-releasing hormone (TRH)mRNA expression in the hypothalamic paraventricular nucleus (PVN), pointing to a major alteration in HPT axis setpoint regulation. A strong decrease in TRHmRNA expression is also present in the PVN of patients with major depression as well as in glucocorticoid-treated patients. By inference, hypercortisolism in hospitalized patients with severe depression or in critical illness may induce down-regulation of the HPT axis at the level of the hypothalamus. In order to start defining the determinants and mechanisms of these setpoint changes in various clinical conditions, it is important to note that an increasing number of hypothalamic proteins appears to be involved in central thyroid hormone metabolism. In recent studies, we have investigated the distribution and expression of thyroid hormone receptor (TR) isoforms, type 2 and type 3 deiodinase (D2 and D3), and the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the human hypothalamus by a combination of immunocytochemistry, mRNA in situ hybridization and enzyme activity assays. Both D2 and D3 enzyme activities are detectable in the mediobasal hypothalamus. D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence region and in tanycytes lining the third ventricle. Combined D2, D3, MCT8 or TR immunocytochemistry and TRHmRNA in situ hybridization indicates that D3, MCT8 and TRs are all expressed by TRH neurons in the PVN, whereas D2 is not. Taken together, these results suggest that the prohormone thyroxine (T4) is taken up in glial cells that convert T4 into the biologically active T3 via the enzyme D2; T3 is subsequently transported to TRH producing neurons in the PVN where it may bind to TRs and/or may be degraded into inactive iodothyronines by D3. This model for thyroid hormone action in the human hypothalamus awaits confirmation in future experimental studies.

Animals↗

PubMed2006

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary.

OBJECTIVE: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry. RESULTS: We found TR isoforms to be expressed most prominently in gonadotropes and - although to a lesser extent - in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression. CONCLUSIONS: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T(4)).

Aged↗

PubMed2006

Thyrotropin, but not a polymorphism in type II deiodinase, predicts response to paroxetine in major depression.

OBJECTIVE: The determinants of response to antidepressant treatment in major depression are unknown at present. The aim of the present study was to establish whether response is predicted by Hypothalamus-Pituitary-Thyroid (HPT) axis parameters or by a recently discovered polymorphism in the enzyme type II deiodinase (DII), which catalyzes the production of T3 in the brain. DESIGN: We analyzed prediction of response to paroxetine treatment by calculating response rates per tertile of HPT-axis parameters and per DII genotype. METHODS: Ninety-eight outpatients with major depression (DSM-IV) were included. Serum concentrations of TSH, FT4 and delta TSH in a DEX/CRH-TRH test were measured. In addition, the presence of a polymorphism in the DII sequence (Thr92Ala) was determined. RESULTS: The overall treatment response was 48 of 98 patients (49%). After exclusion of patients with subclinical hypothyroidism and/or TPO antibodies (n = 16), higher serum TSH significantly predicted response (response rate per tertile from low to high TSH: 36%, 42%, and 67%). Heterozygous patients for the DII polymorphism (44%) had slightly lower serum TSH (P = 0.03) as compared to patients with the wild-type DII (47%). The polymorphism was unrelated to treatment response. CONCLUSION: Higher serum TSH was associated with response to paroxetine in patients with major depression.

Adult↗

PubMed2006

The effects of sex-steroid administration on the pituitary-thyroid axis in transsexuals.

OBJECTIVE: Estrogen and androgen administration modulate the pituitary-thyroid axis through alterations in thyroid hormone-binding globulin (TBG) metabolism, but the effects of sex steroids on extrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion in humans are unknown. DESIGN AND METHODS: We studied 36 male-to-female and 14 female-to-male euthyroid transsexuals at baseline and after 4 months of hormonal treatment. Male-to-female transsexuals were treated with cyproterone acetate (CA) 100 mg/day alone (n = 10) or in combination with either oral ethinyl estradiol (or-EE) 100 microg/day (n = 14) or transdermal 17beta-estradiol (td-E) 100 microg twice a week (n = 12). Female-to-male transsexuals were treated with i.m. testosterone 250 mg twice a week. A t-test was used to test for differences within groups and ANOVA with post hoc analysis to test for differences between the groups. RESULTS: Or-EE increased TBG (100 +/- 12%, P < .001) and testosterone decreased TBG (-14 +/- 4%, P = 0.01), but free T4 did not change. Td-E and CA did not affect TBG concentrations. TSH was not different between groups at baseline or after treatment. CA decreased T3/T4 ratios (-9 +/- 3%, P = 0.04), suggesting that T4 to T3 conversion was lower. Testosterone increased T3/T4 ratios (30 +/- 9%, P = 0.02), which probably reflects higher T4 to T3 conversion. CONCLUSION: Oral but not transdermal estradiol increases TBG, whereas testosterone lowers TBG. Testosterone increases T3/T4 ratios. Estradiol does not affect T3/T4 ratios, irrespective of the route of administration.

Adult↗

PubMed2005

Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression).

BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether dexamethasone/corticotropin-releasing hormone (DEX/CRH) test parameters were related to the occurrence of relapse in 45 outpatients with clinically remitted major depression. The DEX/CRH test was administered before and after 8 weeks of antidepressant treatment. RESULTS: Posttreatment maximal adrenocorticotropic hormone (ACTH) and maximal cortisol levels, as well as delta ACTH and delta cortisol levels, were significantly higher (all p < .05) among patients who relapsed (n = 22) compared with patients in whom no relapse occurred (n = 23). Higher posttreatment maximal cortisol response on the DEX/CRH test was associated with shorter "relapse-free survival" (p = .05). CONCLUSIONS: In outpatients with clinically remitted major depression, higher posttreatment maximal cortisol levels on the DEX/CRH test were associated with relapse of major depression.

Adolescent↗

PubMed2005

Tracing from fat tissue, liver, and pancreas: a neuroanatomical framework for the role of the brain in type 2 diabetes.

The hypothalamus uses hormones and the autonomic nervous system to balance energy fluxes in the body. Here we show that the autonomic nervous system has a distinct organization in different body compartments. The same neurons control intraabdominal organs (intraabdominal fat, liver, and pancreas), whereas sc adipose tissue located outside the abdominal compartment receives input from another set of autonomic neurons. This differentiation persists up to preautonomic neurons in the hypothalamus, including the biological clock, that have a distinct organization depending on the body compartment they command. Moreover, we demonstrate a neuronal feedback from adipose tissue that reaches the brainstem. We propose that this compartment-specific organization offers a neuroanatomical perspective for the regional malfunction of organs in type 2 diabetes, where increased insulin secretion by the pancreas and disturbed glucose metabolism in the liver coincide with an augmented metabolic activity of visceral compared with sc adipose tissue.

Adipose Tissue↗

PubMed2005

Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3'-triiodothyronine therapy.

INTRODUCTION: Some patients on levothyroxine replacement display significant impairment in psychological well-being, compared with sex- and age-matched controls. Levothyroxine-treated patients can be assumed to derive T3 exclusively from deiodination of T4, which, in the central nervous system, is regulated by type II deiodinase (DII). OBJECTIVE: We investigated whether two recently identified polymorphisms in the DII gene (DII-ORFa-Gly3Asp and DII-Thr92Ala) are determinants of well-being and neurocognitive functioning and associated with a preference for replacement with a combination of T3 and T4. METHODS: Genotypes for both polymorphisms were determined in 141 patients with primary autoimmune hypothyroidism, adequately treated with levothyroxine monotherapy and participating in a randomized clinical trial comparing T4 therapy with T4/T3 combination therapy. Questionnaires on well-being and neurocognitive tests were performed at baseline. RESULTS: Allele frequencies in patients with primary hypothyroidism were similar to those of healthy blood bank donors (32.0 vs. 33.9% for DII-ORFa-Gly3Asp and 40.4 vs. 38.8% for DII-Thr92Ala). DII polymorphisms were not associated with measures of well-being, neurocognitive functioning, or preference for combined T4/T3 therapy. CONCLUSION: The DII-ORFa-Gly3Asp and DII-Thr92Ala polymorphisms do not explain differences in well-being, neurocognitive functioning, or appreciation of T4/T3 combination therapy in patients treated for hypothyroidism.

Adult↗

PubMed2005

Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus.

CONTEXT: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. OBJECTIVE: The aim of this study was to report the distribution of type II and type III deiodinase (D2 and D3) as well as the recently identified T(3) transporter, monocarboxylate transporter 8 (MCT8), in the human hypothalamus. DESIGN: The study included enzyme activity assays, immunocytochemical studies, and mRNA in situ hybridizations in postmortem human hypothalamus (n = 9). RESULTS: D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence, blood vessels, and cells lining the third ventricle. By contrast, both D3 and MCT8 are expressed by neurons of the paraventricular (PVN), supraoptic, and infundibular nucleus (IFN). In support of these immunocytochemical data, D2 and D3 enzyme activities are detectable in the mediobasal human hypothalamus. Combined D2, D3, MCT8, and thyroid hormone receptor immunohistochemistry and TRH mRNA in situ hybridization clearly showed that D3, MCT8, and thyroid hormone receptor isoforms are all expressed in TRH neurons of the PVN, whereas D2 is not. CONCLUSIONS AND IMPLICATIONS: Based on these findings, we propose three possible routes for thyroid hormone feedback on TRH neurons in the human PVN: 1) local thyroid hormone uptake from the vascular compartment within the PVN, 2) thyroid hormone uptake from the cerebrospinal fluid in the third ventricle followed by transport to TRH neurons in the PVN or IFN neurons projecting to TRH neurons in the PVN, and 3) thyroid hormone sensing in the IFN of the mediobasal hypothalamus by neurons projecting to TRH neurons in the PVN.

Adult↗

PubMed2005

Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial.

Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5:1 or 10:1 with LT4 monotherapy. We conducted a double-blind, randomized, controlled trial in 141 patients (18-70 yr old) with primary autoimmune hypothyroidism, recruited via general practitioners. Inclusion criteria included: LT4 treatment for 6 months or more, a stable dose for 6 wk or more, and serum TSH levels between 0.11 and 4.0 microU/ml (mU/liter). Randomization groups were: 1) continuation of LT4 (n = 48); 2) LT4/LT3, ratio 10:1 (n = 46); and 3) LT4/LT3, ratio 5:1 (n = 47). Subjective preference of study medication after 15 wk, compared with usual LT4, was the primary outcome measure. Secondary outcomes included scores on questionnaires on mood, fatigue, psychological symptoms, and a substantial set of neurocognitive tests. Study medication was preferred to usual treatment by 29.2, 41.3, and 52.2% in the LT4, 10:1 ratio, and 5:1 ratio groups, respectively (chi2 test for trend, P = 0.024). This linear trend was not substantiated by results on any of the secondary outcome measures: scores on questionnaires and neurocognitive tests consistently ameliorated, but the amelioration was not different among the treatment groups. Median end point serum TSH was 0.64 microU/ml (mU/liter), 0.35 microU/ml (mU/liter), and 0.07 microU/ml (mU/liter), respectively [ANOVA on ln(TSH) for linear trend, P < 0.01]. Mean body weight change was +0.1, -0.5, and -1.7 kg, respectively (ANOVA for trend, P = 0.01). Decrease in weight, but not decrease in serum TSH was correlated with increased satisfaction with study medication. Of the patients who preferred combined LT4/LT3 therapy, 44% had serum TSH less than 0.11 microU/ml (mU/liter). Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.

Adolescent↗

PubMed2005

Sympathetic and parasympathetic innervation of adipose tissue: metabolic implications.

PURPOSE OF REVIEW: Adipose tissue is of fundamental importance for the integrative physiology of the body by serving metabolic and endocrine functions. The purpose of this review is to evaluate the functions of the autonomic innervation of adipose tissue. RECENT FINDINGS: Different lines of evidence from studies on the sympathetic or parasympathetic innervation of adipose tissue have indicated that the autonomic nervous system modulates the fundamental properties of adipose tissue function and biology at the cellular and molecular level. This is reflected in the modulation of lipolysis/lipogenesis, local insulin sensitivity of glucose and fatty acid uptake, the expression levels of several adipokines in adipose tissue, and the modulation of fat cell number. In general, the function of the sympathetic nervous system can be described in terms of catabolism, whereas the function of the parasympathetic system can be described as anabolic. SUMMARY: Innervation by autonomic nerves modulates glucose and fat metabolism in adipose tissue. It is very tempting to speculate on the effects of shifts in the balance between sympathetic and parasympathetic activity in adipose tissue in (patho)physiological conditions, such as lipodystrophy, type 2 diabetes mellitus, dyslipidemia and other insulin-resistant states.

Adipose Tissue↗

PubMed2005

Thyroid and adrenal axis in major depression: a controlled study in outpatients.

OBJECTIVE: Major depressive disorder has been associated with changes in the hypothalamus-pituitary-thyroid (HPT) axis and with hypercortisolism. However, the changes reported have been at variance, probably related to in- or outpatient status, the use of antidepressant medication and the heterogeneity of depression. We therefore conducted a controlled study in unipolar depressed outpatients who had been free of antidepressants for at least 3 months. DESIGN: We assessed endocrine parameters in 113 depressed outpatients and in 113 sex- and age-matched controls. METHODS: Patients were included if they had a major depression according to a Structural Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM), fourth edition (SCID-IV) and if they had a 17-item Hamilton rating scale for depression (HRSD) score of > or =16. Endocrine parameters contained serum concentrations of TSH, (free) thyroxine, tri-iodothyronine, cortisol, thyroid peroxidase (TPO) antibody titre and 24-h urinary excretion of cortisol. RESULTS: The serum concentration of TSH was slightly higher in depressed patients as compared with controls (P < 0.001), independent of the presence of subclinical hypothyroidism and/or TPO antibodies (n = 28). All other HPT axis parameters were similar in both groups. The 24-h urinary cortisol excretion was similar in patients and controls. In atypical depression, serum cortisol was lower than in non-atypical depression (P = 0.01). Patients with neither melancholic depression nor severe depression (HRSD > or =23) had altered endocrine parameters. Finally, serum TSH values could not be related to cortisol values. CONCLUSION: When compared with matched control subjects, outpatients with major depression had slightly higher serum TSH, while urinary cortisol levels were similar. Furthermore, we observed lower serum cortisol in atypical depression than in non-atypical depression.

Adrenal Glands↗

PubMed2005

Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism.

OBJECTIVE: Hypothyroidism is associated with neurocognitive impairment. Sparse data suggest that treatment of hypothyroidism, resulting in a return to euthyroidism, may be associated with only partial recovery of overall neurocognitive functioning. The aim of this study was to assess neurocognitive functioning and well-being in euthyroid patients with primary hypothyroidism on adequate thyroxine (T4) treatment. We also investigated whether serum TSH and thyroid antibodies are determinants of neurocognitive functioning and well-being. DESIGN: We assessed neurocognitive functioning and well-being in 141 patients with primary hypothyroidism. METHODS: Neurocognitive test results and scores on questionnaires measuring well-being of 141 patients were compared with the reference values for these tests as published and used in Dutch clinical neuropsychological practice. Assessment of neurocognitive functioning included tests for cognitive or psychomotor speed, attention, working memory as well as learning and memory. Well-being was measured with the Symptom Check List-90 total score and the Rand 36-item Health Survey subscales for 'mental health' and 'vitality'. RESULTS: Patients showed poor performance on various domains of neurocognitive functioning compared with mean standard reference values, especially on a complex attention task and on verbal memory tests. Levels of well-being were significantly lower for patients compared with those of the general population. Neither serum TSH nor thyroid antibodies were determinants of neurocognitive functioning and well-being. CONCLUSION: The results of this study suggest that neurocognitive functioning as well as psychological well-being may not be completely restored in patients with hypothyroidism, despite T4 treatment.

Adult↗

PubMed2004

Thyroid hormone receptor expression in the human hypothalamus and anterior pituitary.

In the present study, we describe for the first time the distribution of thyroid hormone receptor (TR) isoforms in the human postmortem hypothalamus and anterior pituitary using immunocytochemistry. We used a set of polyclonal antisera raised against the specific isoforms of the human TR. The distribution of TR alpha 1, alpha 2, beta 1, and beta 2 was studied in consecutive sections of six hypothalami and pituitaries. Staining intensity showed strong interindividual variation but was consistently present in the infundibular nucleus, paraventricular nucleus, and supraoptic nucleus. In addition, strong TR immunoreactivity was observed in the anterior pituitary. Neuropeptide Y and proopiomelanocortin mRNA-positive cells in the infundibular nucleus, which were studied in three other hypothalami, appeared not to express TRs, and thus, the neurons expressing TRs in the human mediobasal hypothalamus remain to be characterized.

Aged↗