Pituitary-thyroid Axis Research Articles

Effects of submaximal aerobic exercise on thyroid hormones in hypoxic conditions in trained young men

Background: There are many conflicting opinions regarding the effects of hypoxia on thyroid hormones in different situations. This study evaluates the effect of exercise-induced hypoxia on thyroid hormones and thyroid-stimulating hormone (TSH) in trained young men. Materials and Methods: The participants consisted of 17 healthy men, aged 20-24 years, with mean maximal oxygen uptake and body mass index of 48.6 ± 3.96 ml/kg/min and 21.6 ± 0.91 kg/m 2 , respectively. They did 30-min running on treadmill, at the intensity of 70% of maximal heart rate, in normoxia and three different levels of simulated hypoxic conditions at 2750, 3250, and 3750 m heights. The sessions were interspaced with 72-hour resting breaks. Blood samples for hormonal assays were obtained before exercise and at 0 h and 1 h after exercise. Results: Data analysis, using mixed models, showed no statistically significant hormonal difference among the hypoxic conditions (P > 0.05) except increased thyroxin levels following exercise in all sessions , which were significant only in normoxia and 2750 m height (P < 0.05), without any significant changes in serum triiodotyronine and TSH. Conclusion: With respect to different reports surrounding the effects of high-altitude-induced hypoxia on pituitary-thyroid axis (including stimulatory, inhibitory, or changeless effects), this study revealed only significant increased thyroxin level at 1200 (normoxia) and 2750 m heights, following exercise. These contradictory findings may be attributed to the degree of prescribed hypoxia, planning of natural or simulated height, activity level and type, and study duration. However, for a precise conclusion, further research is recommended.

Revisiting Thyroid Hormones in Schizophrenia

Thyroid hormones are crucial during development and in the adult brain. Of interest, fluctuations in the levels of thyroid hormones at various times during development and throughout life can impact on psychiatric disease manifestation and response to treatment. Here we review research on thyroid function assessment in schizophrenia, relating interrelations between the pituitary-thyroid axis and major neurosignaling systems involved in schizophrenia's pathophysiology. These include the serotonergic, dopaminergic, glutamatergic, and GABAergic networks, as well as myelination and inflammatory processes. The available evidence supports that thyroid hormones deregulation is a common feature in schizophrenia and that the implications of thyroid hormones homeostasis in the fine-tuning of crucial brain networks warrants further research.

Congenital Hypothyroidism with Gland in situ is More Frequent than Previously Thought

OPINION article Front. Endocrinol., 15 February 2012Sec. Thyroid Endocrinology https://doi.org/10.3389/fendo.2012.00018

Resistance to thyroid hormone is modulated in vivo by the nuclear receptor corepressor (NCOR1)

Mutations in the ligand-binding domain of the thyroid hormone receptor β (TRβ) lead to resistance to thyroid hormone (RTH). These TRβ mutants function in a dominant-negative fashion to interfere with the transcription activity of wild-type thyroid hormone receptors (TRs), leading to dysregulation of the pituitary-thyroid axis and resistance in peripheral tissues. The molecular mechanism by which TRβ mutants cause RTH has been postulated to be an inability of the mutants to properly release the nuclear corepressors (NCORs), thereby inhibiting thyroid hormone (TH)-mediated transcription activity. To test this hypothesis in vivo, we crossed Thrb(PV) mice (a model of RTH) expressing a human TRβ mutant (PV) with mice expressing a mutant Ncor1 allele (Ncor1(ΔID) mice) that cannot recruit a TR or a PV mutant. Remarkably, in the presence of NCOR1ΔID, the abnormally elevated thyroid-stimulating hormone and TH levels found in Thrb(PV) mice were modestly but significantly corrected. Furthermore, thyroid hyperplasia, weight loss, and other hallmarks of RTH were also partially reverted in mice expressing NCOR1ΔID. Taken together, these data suggest that the aberrant recruitment of NCOR1 by RTH TRβ mutants leads to clinical RTH in humans. The present study suggests that therapies aimed at the TR-NCOR1 interaction or its downstream actions could be tested as potential targets in treating RTH.

Hypothyroidism in preterm infants following normal screening

Congenital hypothyroidism is screened for in the UK using blood spot thyroid-stimulating hormone (TSH) screening at 5-8 d of age. Although standards are set by the UK Newborn Screening Programme Centre, there are variations in TSH cut-offs used. The introduction of repeat screening of preterm babies at 36 weeks' gestational age in 2005 was controversial in its utility and timing. Two cases of preterm babies are presented, who had normal blood spot TSH values on the first test and who became screen positive when re-tested at term. The first with Trisomy 21 was born at 29 + 6 weeks with an initial blood spot TSH of 3.3 mU/L rising to 263 mU/L at term-corrected gestational age (plasma TSH 476.5 mU/L). The second was born at 24 + 6 weeks' gestational age and on day 7, the heel prick blood spot TSH was <2 mU/L, rising to 6.4 mU/L at 36 weeks corrected gestational age. After a barium enema, the plasma TSH increased to 66.6 mU/L with a free thyroxine of 7.6 pmol/L at day 101. Both cases were treated with thyroxine until death due to complications of prematurity. These cases illustrate the difficulties in screening for congenital hypothyroidism in preterm infants, due to the immaturity of the hypothalamo-pituitary-thyroid axis, and the effect of intercurrent illness and drugs on thyroid function. Despite a reassuring published review of 2200 preterm infants, these cases suggest that it may be unwise not to re-screen ex-preterm infants for congenital hypothyroidism at term.

Alteration of Hypothalamic–Pituitary–Thyroid Axis Function in Non-Small-Cell Lung Cancer Patients

The aim of this study was to evaluate the hypothalamic-pituitary-thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light-dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a negative correlation in both groups. For FT4 versus IL-2, a negative correlation was found in C but not for H, whereas TSH versus TRH showed no correlation for either group. Both groups were found to be similarly synchronized to the 24-hour sleep-wake schedule, but HPT axis function was altered in patients suffering from lung cancer. When compared with healthy controls, cancer patients showed modifications of hormone serum levels overall and a negative correlation between individual TRH and FT4 levels.

Phytoestrogens and thyroid hormone levels in the cerebrospinal fluid of ewes fed red clover silage

In sheep, phytoestrogens are known to act at various levels on the hypothalamo–pituitary–gonadal axis, as well as the hypothalamo–pituitary–thyroid axis. The levels of genistein and daidzein and their metabolites, p-ethylphenol and equol, in the cerebrospinal fluid (CSF) were studied in ewes fed red clover silage. Moreover, to test the hypothesis that phytoestrogens may affect the access of thyroid hormones in the brain, the concentrations of both total (TT4) and free thyroxine (fT4) in the blood and CSF, were recorded. In the CSF, daidzein, equol and p-ethylphenol were present, but genistein absent. The total daidzein concentration increased from an undetectable level at 2h, to 0.11±0.05μM at 6h after feeding, representing 13.1% of the daidzein measured in the blood. Gradual increases in equol, from an undetectable level at 2h, to 0.24±0.13μM at 6h after feeding (5.1% of that in blood), and in p-ethylphenol, from 0.03±0.02μM at 2h to 1.7±0.74μM at 6h after feeding (0.1–5.8% of that in blood) were recorded. In sheep fed a phytoestrogen rich diet, the blood concentration of TT4 was lower (P<0.05), but the concentration and the percentage of free T4 (fT4) higher (P<0.01) than in the control sheep. In the CSF, the TT4 concentration was similar in both groups, but the concentration and percentage of fT4 was higher in sheep fed a phytoestrogen rich diet. It could be assumed that (i) in sheep, reproductive disorders, at the base of the hypothalamus, following phytoestrogen consumption are evoked by daidzein and equol, its metabolite, rather than genistein, and (ii) phytoestrogens affect the brain's ability to access T4 in the blood.

Central NPY-Y5 receptors activation plays a major role in fasting-induced pituitary–thyroid axis suppression in adult rat

Neuropeptide Y (NPY) inhibits TRH neurons in fed state, and hypothalamic NPY higher expression during fasting has been proposed to be involved in fasting-induced suppression of the hypothalamus-pituitary–thyroid (HPT) axis. We investigated the role of central Y5 receptors in the control of thyrotropin (TSH) and thyroid hormone (TH) secretion. Fed and fasting rats received twice daily central injections (3rd ventricle) of Y5 receptor antagonist (CGP71683; 15nmol/rat) for 72h. Fasted rats also received a single central injection of CGP71683 (15nmol/rat) at the end of 72h of fasting. In fed rats, Y5 receptor blockade reduced total food intake by 32% and body mass by almost 10% (p<0.01), corroborating the role of this receptor in food intake control. 72h-fasted rats exhibited a 4-fold increase in serum TSH (p<0.001), 1h after a single injection of Y5 antagonist. Also with multiple injections during 72h of fasting, Y5 blockade resulted in activation of thyroid axis, as demonstrated by a 3-times rise in serum T4 (p<0.001), accompanied by unchanged TSH and T3. In fed rats, the chronic central administration of CGP71683 resulted in reduced total serum T4 without changes in free T4 and TSH. Serum leptin and PYY were not altered by the NPY central blockade in both fed and fasted rats, suggesting no role of these hormones in the alterations observed. Therefore, the inhibition of central Y5 neurotransmission resulted in activation of thyroid axis during fasting suggesting that NPY-Y5 receptors contribute to fasting-induced TSH and TH suppression.

Chronobiologic study of neuro-endocrine axis hormone sequence signalling in healthy men

The neuro-endocrine system function is characterized by a large number of circadian processes that signal each other in sequence with different rhythm phases over 24 h. The morning peak of cortisol secretion and the nightly peak in melatonin secretion are well-known physiological phenomena. Thyroid-stimulating hormone (TSH) secretion shows higher levels at night, whereas free thyroxine (FT4) levels do not seem to change with circadian rhythmicity. Similarly, growth hormone (GH) is secreted with higher levels at night, but insulin-like growth factor (IGF)-1 production shows only minor fluctuations over 24 h. In order to look for rhythmicity and phasing (acrophase, Ø) in the dynamics of variation over 24 h, we investigated adrenal and pineal gland, pituitary-thyroid axis, and GH-IGF-1 axis secretions of cortisol, melatonin, TSH, FT4, GH and total IGF-1 in serum levels every 4 h for 24 h from 11 healthy men, age: 35–53 years. Circadian rhythmicity was evaluated for original values and for the fractional variation (FV) between single time point values that was calculated to evaluate the percentage change in rise and fall. A 24 h cosine significantly described the circadian waveform for serum levels in cortisol, melatonin, TSH and GH (Ø = 07:48 h, 01:35 h, 23:32 h, 00:00 h, respectively), while a 12 h cosine significantly described two peaks for serum levels in FT4 (Ø = 09:44 h and 21:44 h, P = 0.038), and in IGF-1 (Ø = 07:40 h and 19:40 h, P = 0.013). A 24 h cosine also significantly described the circadian waveform for FV of cortisol (02:00 h), melatonin (22:29 h), FT4 (05:14 h), and GH (21:19 h), while a 12 h cosine significantly described two peaks for FV of TSH (04:28 h for fall and 16:28 h for rise), whereas FV of IGF-1 did not show a rhythmic pattern. Thus, maximal FV estimated by 24 h Øs preceded maximal serum levels by ∼6 h for cortisol and TSH, ∼5 h for FT4, ∼3 h for melatonin, ∼2.5 h for GH, and ∼1 h for IGF-1. When comparing 24 h Øs for serum levels of hormone pairs, the peak for melatonin preceded that for cortisol by 6 h, the peak for TSH preceded the first peak of FT4 by 10.5 h, and the peak for GH preceded that for IGF-1 by 8 h. When comparing FV pairs, the peak for melatonin surge preceded that for cortisol by ∼3.5 h, the peak for TSH surge preceded that for FT4 by ∼13 h, and the peak for GH rise preceded that for IGF-1 ∼10 h. In conclusion, the neuro-endocrine system function is characterized by circadian organization, with individual components showing different phasic patterns of time-related variations, and this array of rhythms undoubtedly underlies the maintenance of stable, but rhythmic and thus predictive, homeostatic processes in the human body.

Linkage and association analysis of hyperthyrotropinaemia in an Alpine population reveal two novel loci on chromosomes 3q28-29 and 6q26-27

BackgroundThyroid hormones have important roles in growth, development and control of metabolism, and their dysregulation can lead to disease.ObjectivesTo identify genes contributing to hyperthyrotropinaemia.Design, setting, participantsLinkage and association analyses using...

Immune–endocrine interactions in treated and untreated cats naturally infected with FIV

Feline immunodeficiency virus (FIV) is a lentivirus that causes a progressive disruption of immune function in cats. The neuroendocrine and immune systems communicate bidirectionally, mediated by cytokines such as tumour necrosis factor-α (TNF), several interleukins (IL-1, IL-6, IL-10), and through signals induced by the ratio of IL-10 to IL-12. FIV can affect both pituitary adrenal and thyroid axis function. Twenty FIV-infected cats in similar stages of the disease were evaluated for six months. A cross-sectional study in which the twenty cats were divided into two groups was performed. Ten were treated with Zidovudine (ZDV: 5 mg/kg/d, PO, q12 h, for six months) and 10 were untreated. Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, T4, FT4, T3, IL-10, IL-12 and viral load (VL) were evaluated after six months. ACTH was found in significantly lower concentrations ( p < 0.0001) in the treated group whereas cortisol did not show significant differences between the two groups. Both T4 and FT4 had high values in untreated individuals ( p < 0.001) compared with Zidovudine treated cats. T3 did not show significant differences between the two groups. Both IL-10 and IL-12 were found in significantly higher concentrations in ZDV treated cats ( p < 0.001). By contrast, the IL10/IL-12 ratio values were significantly lower in untreated cats. Viral load was significantly lower in the treated cats after six months of therapy, compared with values detected pre-treatment ( p < 0.002). Untreated cats showed a significant increase of VL ( p < 0.04) compared with the values at the beginning of the study. In treated cats, VL showed lower numbers of viral copies than in untreated cats ( p < 0.01). In summary, Zidovudine treatment appeared to contribute to the normalization of both the adrenal and thyroid axes. This effect could be attributed to the decrease observed in VL, resulting in a change in cytokine patterns.

New American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidism: Significant Progress for the Clinician and a Guide to Future Research

New American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidism: Significant Progress for the Clinician and a Guide to Future Research

Thyroid hormones response in simulated laboratory sprint duathlon

Alvero-Cruz JR, Ronconi M, Carrillo de Albornoz M, Garcia-Romero JC, Rosado-Velazquez D, de Diego Acosta AM. Thyroid hormones response in simulated laboratory sprint duathlon. J. Hum. Sport Exerc. Vol. 6, No. 2, pp. 323-327, 2011. Increased activity of the pituitary-thyroid axis, plays a role in adaptations to exercise. The aim of this study was to assess changes in thyroid hormones (TH) in a simulated laboratory competition of sprint duathlon. Eight duathletes trained males [mean (SD), age 24.8 (6.8) years, height 174.4 (6.8) cm, body mass 67.12 (8.1) kg] participate in this study. The duathletes performed two graded maximal exercise in random order, one on cycle-ergometer and other on a treadmill, to determine their VO2peak. Simulated laboratory competition was carried out during 20 min Run1, 40 min Bike and 12 min Run2 sectors. A blood sample was drawn to determine serum concentrations of TSH, T4, T3 and were analyzed by chemiluminiscence. A one-way analysis of variance (ANOVA) was used to analyze differences among sectors and Pearson correlation coefficients were calculated between TH and exercise intensity. Athletes perform a high intensity exercise reaching high mean values of aerobic power (89.6 ± 6.1, 85.1 ± 8.7 and 87.1 ± 6.9 of %VO2 in Run1, Bike and Run2 respectively). TSH shown differences between -30 min and Run2 (p 0.05). Significant inverse correlations between T3 (r= -0.86) and T4 (r= -0.86) and percent VO2 (p<0.01) were found. The hormones of the hypothalamic-pituitary-thyroid axis show significant changes in TSH. Thus our results suggest, at least partly, an association between both T3 and T4 with intensity of competition as percent of VO2 in athletes with normal thyroid function during intense and submaximal exercise simulating a duathlon competition. The decrease of TH in relation to exercise intensity is due to the use of peripheral tissues. In conclusion our findings suggest that thyroid function might play a role related to exercises performed to

What should be done when thyroid function tests do not make sense?

Interpretation of thyroid function tests (TFTs) is generally straightforward. However, in a minority of contexts the results of thyroid hormone and thyrotropin measurements either conflict with the clinical picture or form an unusual pattern. In many such cases, reassessment of the clinical context provides an explanation for the discrepant TFTs; in other instances, interference in one or other laboratory assays can be shown to account for divergent results; uncommonly, genetic defects in the hypothalamic-pituitary-thyroid axis are associated with anomalous TFTs. Failure to recognize these potential 'pitfalls' can lead to misdiagnosis and inappropriate management. Here, focusing particularly on the combination of hyperthyroxinaemia with nonsuppressed thyrotropin, we show how a structured approach to investigation can help make sense of atypical TFTs.

Alterations of the thyroid structure and function in experimental hypopinealism

The pituitary-thyroid axis of young sexually mature rabbits kept under a 24-hour daylight photoperiod was shown to undergo phase-modulated variations of hormonal activity with its initial increase (during the first month) and subsequent progressive decrease (within 2-5 months after the onset of exposure to light). These changes correlated with the time-dependent fall in the blood T3, T4, and TSH levels. Simultaneously, the animals developed pathological changes in the histological structure of the thyroid gland similar to those in patients with secondary or tertiary hypothyroidism. It is concluded that hormonal and structural changes in the thyroid gland during long-term hypopinealism should be regarded as an experimental model of hypothyroidism of neuroendocrine origin.

Glutaminyl Cyclase Knock-out Mice Exhibit Slight Hypothyroidism but No Hypogonadism: IMPLICATIONS FOR ENZYME FUNCTION AND DRUG DEVELOPMENT

Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate (pGlu) residues at the N terminus of peptides and proteins. Hypothalamic pGlu hormones, such as thyrotropin-releasing hormone and gonadotropin-releasing hormone are essential for regulation of metabolism and fertility in the hypothalamic pituitary thyroid and gonadal axes, respectively. Here, we analyzed the consequences of constitutive genetic QC ablation on endocrine functions and on the behavior of adult mice. Adult homozygous QC knock-out mice are fertile and behave indistinguishably from wild type mice in tests of motor function, cognition, general activity, and ingestion behavior. The QC knock-out results in a dramatic drop of enzyme activity in the brain, especially in hypothalamus and in plasma. Other peripheral organs like liver and spleen still contain QC activity, which is most likely caused by its homolog isoQC. The serum gonadotropin-releasing hormone, TSH, and testosterone concentrations were not changed by QC depletion. The serum thyroxine was decreased by 24% in homozygous QC knock-out animals, suggesting a mild hypothyroidism. QC knock-out mice were indistinguishable from wild type with regard to blood glucose and glucose tolerance, thus differing from reports of thyrotropin-releasing hormone knock-out mice significantly. The results suggest a significant formation of the hypothalamic pGlu hormones by alternative mechanisms, like spontaneous cyclization or conversion by isoQC. The different effects of QC depletion on the hypothalamic pituitary thyroid and gonadal axes might indicate slightly different modes of substrate conversion of both enzymes. The absence of significant abnormalities in QC knock-out mice suggests the presence of a therapeutic window for suppression of QC activity in current drug development.

Thyroid gland lesions in organohalogen contaminated East Greenland polar bears (Ursus maritimus)

Thyroid gland histology was examined in 20 organohalogen contaminant (OHC)-exposed East Greenland polar bears (Ursus maritimus). OHC concentrations measured in subcutaneous adipose tissue were between 3556 and 28,670 ng g−1 lw for polychlorinated biphenyls (ΣPCB51), 9 and 3403 ng g−1 lw for the sum of organochlorine pesticides (hexachlorocyclohexanes, hexachlorobenzene, chlordanes, dichlorodiphenyltrichloroethanes, and dieldrin), and from 21 to 130 ng g−1 lw for polybrominated diphenyl ethers. Histological examinations revealed that 12 of the bears (10 males aged 3–19 years and two females aged 4–7 years) had normal thyroid tissue while eight bears (40%) of varying ages and genders (three males aged 3–9 years and five females aged 4–25 years) showed clear histological lesions including parafollicular C-cell proliferation, nodular hyperplasia, and interstitial fibrosis. No significant differences were found in prevalence of thyroid gland lesions between males and females. Similarly, no marked difference was found in mean age between individuals with and without lesions. There was no significant difference in OHC mean concentrations between males and females or between individuals with and without lesions. Despite no documented relationship to OHC concentrations in adipose tissue, it is worth noting that the lesions were similar to that of OHC exposed lab and wildlife contaminated mammals. Since the lesions were not associated with age or gender, other environmental factors such as energetic stress and autoimmunity/genetic predisposition also need to be considered. It is therefore possible that OHCs, in combination with other environmental and intrinsic factors described in the literature, may interfere with the hypothalamic–pituitary–thyroid axis (HPT axis) resulting in endocrine perturbations in East Greenland polar bears.

Effect of a combined iodine and selenium supplementation on I and Se status of cows and their calves

Iodine (I) and selenium (Se) deficiencies are commonly reported in cattle, however, there are also studies regarding a very high iodine supply. The aim of the study was to determine the long-term effect of I and Se supplementation on non-pregnant cows, pregnant cows and their calves. The hypothalamus pituitary axis was investigated (TSH, T4, T3 assays) during a TRH challenge on non-pregnant cows. Twenty-four cows, half of them pregnant, were assigned into 2 diet-groups, one group with a low I (0.45 ppm) and Se (0.15 ppm) diet (LISe), the other with a high I (5.45 ppm) and Se (0.45 ppm) diet (HISe), for a period of 120 days. Nutritional (plasma iodide, urinary I, plasma Se, I content in colostrum and foetal fluids) and functional (thyrotropin, thyroid hormones, glutathione-peroxidase activity in erythrocytes) markers of I and Se status were assayed in dams at regular intervals for 120 days and in their calves at birth. A TRH challenge was performed on 8 non-pregnant cows at day 110 of the trial. At the end of the study, I and Se nutritional markers were higher in dams in the HISe group, compared to the LISe group, except for plasma Se. At birth, I nutritional markers in calves in the HISe group were higher compared to the LISe group. Reactivity of the pituitary–thyroid-axis was not influenced by I and Se supplementation. I and Se supplementation is efficient in improving newborn status.

Prediction of early pregnancy maternal thyroid impairment in women affected with unexplained recurrent miscarriage

Proper maternal thyroid function is necessary for a successful pregnancy. In order to identify women who may experience miscarriage due to transient impairment of the pituitary-thyroid axis in early pregnancy, we aimed to investigate the ratio between basal and peak thyroid stimulating hormone (TSH) [following stimulus with thyrotrophin-releasing hormone (TRH)] in euthyroid women with unexplained recurrent miscarriage (RM). We have established a 'iTSHa index' (TSH increase after TRH adjusted for the levels of basal TSH), determining TSH serum levels at time 0 and 20 min after TRH stimulus in 463 consecutive women attending two antenatal care units for two or more miscarriages occurring within the first 10 weeks of pregnancy. The mean basal TSH serum levels were higher (P < 0.001) in RM women [2.1 μIU/ml; 95% confidence interval (CI): 2.0-2.2] compared with the controls (1.3 μIU/ml; 95% CI: 1.2-1.4). Establishing serum TSH at an individual level, a large overlap was observed and the receiver operating characteristic curves did not allow us to find an optimal cut-off point with an adequate sensitivity/specificity ratio. Therefore, we suggest a novel statistical model, the 'iTSHa index' (available on www.afar.it/tsh-trh-miscarriage), that is capable of identifying women with RM due to transient thyroid function impairment of the early pregnancy, in particular when baseline serum TSH is less than 1.5 μIU/ml, i.e. well below the conventional upper cut-off indicated as 'safe' in those who want to conceive. A transient impairment of thyroid function in early pregnancy may cause an inadequate adaptation to the increased thyroid requirement and may be implicated in RM. The evaluation of the proposed iTSHa index, if validated in a larger cohort of patients, may provide information useful to identifying a subset of healthy women, without evidence of thyroid dysfunction or autoimmunity and a TSH in the low-normal reference range, who may be at risk of RM.

The pituitary–thyroid axis during the parr–smolt transformation of Coho salmon, Oncorhynchus kisutch: Quantification of TSH β mRNA, TSH, and thyroid hormones

The objective of this investigation was to quantify pituitary thyroid stimulating hormone (TSH) β mRNA, pituitary and plasma TSH and plasma thyroid hormone levels during the parr–smolt transformation of Coho salmon that occurs in spring from February to May. The status of the pituitary–thyroid axis was assessed using an RNase protection assay for pituitary TSH β mRNA and radioimmunoassays for salmon pituitary and plasma TSH and thyroid hormones. TSH β mRNA was highest during late winter (February) (4.9 pg/μg DNA) and gradually declined during spring (2.3 pg/μg DNA). In contrast, pituitary and plasma TSH levels showed a small, but statistically non-significant change during smoltification. Despite minimal change in plasma TSH levels, characteristically large increases in plasma T4 (January-3.3 ng/ml to April-10.2 ng/ml) and significant, but modest increases in plasma T3 (February-2.4 ng/ml to April-5.8 ng/ml) were observed. Regression analysis showed a significant positive relationship between plasma T4 and T3 and negative relationship between plasma T3 and pituitary TSH β mRNA. However, all other relations were not significant. These data suggest a significant role for peripheral regulation (i.e. T4–T3 conversion, change in tissue sensitivity, hormone degradation rate) as well as evidence of central regulation via negative feedback at the level of the pituitary gland in regulation of thyroid activity in salmon. Furthermore, the increased thyroid sensitivity to TSH (shown previously), in the face of relatively constant plasma TSH levels, may be the major factor responsible for the increased thyroid activity observed during smoltification.