Changes in whole body concentrations of thyroid hormones and cortisol in metamorphosing conger eel

Summary To clarify the hormonal regulation of metamorphosis of the conger eel (Conger myriaster), changes in whole body concentrations of thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), and cortisol during metamorphosis were examined, as well as the changes in the histological activity of the thyroid gland. In larvae before metamorphosis, T₄ and T₃ levels were less than 5 and 0.15 ng·g^-1 respectively. Levels of T₄ increased to about 30 ng·g^-1 during early metamorphosis, and decreased subsequently. Levels of T₃ increased gradually in early metamorphosis, and then increased abruptly to about 2.0 ng·g^-1 in late metamorphosis. Before metamorphosis, cortisol levels of the leptocephali less than 11 cm in total length were greater than 200 ng·g^-1. Cortisol levels decreased rapidly in larger premetamorphic leptocephali, and low levels were maintained throughout the metamorphic period. Histological observation revealed an activation of the thyroid gland in early metamorphosis; thyroid follicle epithelial cells became columnar and their nuclei larger. Active uptake of colloid by these cells and intensive vascularization of the gland were also observed. By the end of metamorphosis, follicle epithelial cells became squamous, indicating a low level of glandular activity. These results suggest that thyroid hormone plays an important role in regulation of conger eel metamorphosis.Abbreviations AL anal length - TL total length - T ₃ triiodothyronine - T ₄ thyroxine     

The effect of ACTH therapy on serum dehydroepiandrosterone, androstenedione, testosterone and 5 alpha-dihydrotestosterone in infants

Serum concentrations of dehydroepiandrosterone (DHEA), androstenedione, testosterone, 5 alpha-dihydrotestosterone and cortisol were measured in 10 infants (age 5-22 months) before, during and after 6-weeks of ACTH therapy for infantile spasms. During therapy, their mean DHEA concentrations increased 2.3-fold, androstenedione 12.3-fold, testosterone 2.7-fold, 5 alpha-dihydrotesterone 2.5-fold and cortisol 2.9-fold compared to pre-therapy values. Serum dehydroepiandrosterone sulphate (DHEA-S) concentrations were also increased during ACTH therapy above the normal prepubertal range. Three days after the cessation of ACTH treatment, all androgens had returned to the pre-therapy level. We conclude: At least in pharmacologic doses ACTH alone stimulates adrenal androgen secretion in infants, excluding the necessity of a separate adrenal androgen stimulating hormone.     

Dynamics of Thyroid Hormones at Early Stages of Development of the Sturgeon Acipenser güldenstadti

Using radioimmunological method, the level and dynamics of thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃) were studied in eggs, embryos, and pre-larvae of the Russian sturgeon Acipenser güldenstadti L. The level of hormones in eggs was higher than in the individuals at the stage of hatching. In embryogenesis the content of T₄ and T₃ hormones changed simultaneously, while in pre-larvae, synchronization was absent. The maximal T₄ values in sturgeon pre-larvae were recorded not long before transition to active nutrition. The T₄ level was statistically significantly higher in eggs and larvae developed from the eggs with a high degree of fertility. The problem of participation of thyroid hormones in processes of development and formation of adaptive mechanisms in early ontogenesis of sturgeons is discussed.     

Diagnostic Confusion Attributable to Spurious Elevation of Both Total Thyroid Hormone and Thyroid Hormone Uptake Measurements in the Setting of Autoantibodies: Case Report and Review of Related Literature

ObjectiveTo review the effect of thyroid autoantibodies on thyroid function assays and to present a case in which thyroid autoantibodies resulted in spurious assay readings for both total thyroid hormone levels and thyroid hormone uptake measurements.MethodsWe present a detailed case, including serial laboratory data, and review the relevant literature.ResultsA 61-year-old man with a history of autoimmune disease presented for evaluation of abnormal results of thyroid function tests. The patient had been treated for hypothyroidism with levothyroxine and was noted to have an elevated total thyroxine (T₄) level in the setting of a low total triiodothyronine (T₃) value and a mildly elevated thyrotropin concentration. He had been referred for evaluation of a presumed deiodinase deficiency that impaired conversion of T₄ to T₃. During treatment with levothyroxine, these test results were confirmed, and the patient was also found to have an elevated T₄ uptake. These findings were initially thought to be due to an excess of transthyretin; however, more extensive testing revealed that the patient had an autoantibody to T₄ that interfered with the assays for both T₄ and T₄ uptake.ConclusionAutoantibodies to both T₃ and T₄ have been described. Such antibodies are not uncommon in patients with thyroid disease. On rare occasions, these antibodies may cause spurious assay readings and obscure the diagnosis. To our knowledge, this is the first report in which both the total T₄ level and the T₄ uptake were elevated because of the presence of autoantibodies. Thyroid hormone autoantibodies must be considered when clinicians encounter patients with unexplained abnormal results of thyroid function tests. (Endocr Pract. 2008; 14:738-742)     

Diurnal rhythms of plasma growth hormone,somatostatin, thyroid hormones,cortisol and glucose concentrations in rainbow trout,Oncorhynchus mykiss,during progressive food deprivation

Abstract

The diurnal patterns of changes in plasma cortisol, growth hormone (GH), somatostatin‐14 (SRIF), thyroid hormones (L‐thyroxine, T₄ and triiodo‐L‐thyronine, T₃) and glucose were investigated in rainbow trout, Oncorhynchus mykiss, both during single meal‐feeding and during a progressive fast of 13 weeks. All measured variables exhibited a diurnal pattern in fed rainbow trout, most of which appeared to be correlated with the time of feeding (30–60 min after the onset of light), while additional changes, associated with the scotophase were also found for cortisol. Although fasting had no affect on mean daily plasma cortisol or SRIF concentrations, there was a progressive increase in mean daily plasma GH concentrations and a progressive decrease in mean daily plasma thyroid hormone and glucose concentrations associated with fasting. However, for GH, significant changes were not evident until week 10 of the fast. In addition, fasting appeared to phase‐shift the diurnal patterns of plasma GH, cortisol and glucose concentrations; the consequence of such a shift is that conclusions as to the effects of fasting, if based on a single time of sampling, may be flawed.     

Effects of cortisol administration on development of the thyroid and adrenal axes in rats

Intraperitoneal (IP) injections of cortisol were administered to neonatal male rats on postnatal days 1 to 4. Plasma triiodothyronine (T₃), thyroxine (T₄) and corticosteroids were determined on days 5, 10, 13, 16, 20, 30 and 60 of age, and all animals were weighed weekly. Neonatal cortisol treatment resulted in depressed body weight gain and transient depression in plasma T₄. These results indicate that while body weight is significantly affected by cortisol treatment ontogenic patterns of plasma T₃, T₄ and corticosteroids develop normally.     

Effects of early neonatal thyroxine treatment on development of the thyroid and adrenal axes in rats

Neonatal male rats were treated with intraperitoneal (IP) injections of thyroxine on postnatal days 1 to 4. Plasma triiodothyronine (T₃), thyroxine (T₄), and corticosteroids were determined on days 5, 10, 13, 16, 20, 30, and 60 of age, and all animals were weighed weekly. Neonatal thyroxine treatment resulted in reduced body weight throughout the entire test period, decreased T₃ and T₄ until day 60 of age, and elevated corticosteroids on days 5 to 13 of age. These results demonstrate that early neonatal T₄ treatment affects the ontogeny of both thyroid and adrenocortical hormones, and suggest that these developmental changes should be considered when evaluating the consequences of T₄ treatment during the early neonatal period.     

Changes in the hypothalamo-pituitary-adrenocortical and hypothalamo-pituitary-thyroid axes in diabetic rats acclimated to moderate hyperthermic environment

We examined the effect of acclimation to moderate hyperthermic environment on the ACTH, TSH, T₃, T₄ and corticosterone level, as well as the relative weight of hypophysis, thyroid and adrenal glands in streptozotocin-diabetic rats. Increased activity of the hypothalamo-pituitary-adrenocortical (HPA) axis has been demonstrated in diabetic animals, whereas insulin treatment restores the changes. Heat acclimation reduces the level of ACTH and corticosterone in control animals and moderates the hormonal disturbances caused by diabetes. Simultaneously, our study revealed impairment in the activity of the hypothalamo-pituitary-thyroid (HPT) axis. Acclimation to 35±1 °C resulted in significantly lower T₃ and T₄ levels in control, diabetic and insulin-treated animals. Relative weight of the hypophysis, thyroid and adrenal glands is decreased in heat-acclimated rats. Our assumption is that there might be a cross tolerance between diabetes and heat acclimation on a hormonal level.     

The influence of inorganic silicon (Si) on pituitary-thyroid axis

The influence of silicon-treatment on the levels of TSH and thyroid hormones was studied in rats. Concentrations of thyrotropin (TSH), triiodothyronine (T₃), and thyroxine (T₄) were estimated in sera of rats receiving per os a soluble silicon compound—sodium metasilicate nonahydrate (Na₂SiO₃·9H₂O), dissolved in the animals' drinking water. An increase in the TSH level in the tested group was observed, without statistically significant differences in T₃ and T₄ concentrations between the two groups of animals. The results provide evidence for the influence of silicon on the endocrine balance. They could also prove that this chemical element is capable of modifying the rate of some hormones' synthesis.     

Dietary selenium status and plasma thyroid hormones in chicks

Experiments were conducted to study the effect of marginal levels of selenium and vitamin E on plasma thyroid hormones of meattype chicks. Plasma thyroxine (T₄) was significantly increased when a semipurified diet was supplemented with either selenium or vitamin E. Triiodothyronine (T₃) was also significantly increased by vitamin E and in one experiment with selenium supplementation. No significant increase in these hormones was observed in birds fed a corn-soybean-meal diet supplemented with these nutrients. Plasma corticosterone level was reduced and weight of the bursa of Fabricius increased by selenium or vitamin E supplementation. These nutrients may be necessary for providing the optimum thyroid conditions for activity of thyroid peroxidase.     

Serum thyroxine levels in patients receiving L-thyroxine suppression or replacement therapy

Serum thyroxine (T₄) and protein-bound iodine (PBI) levels were measured in 140 adult patients receiving L-thyroxine, 0.2 or 0.3 mg. daily for at least six months, as suppression or replacement therapy. All were judged to be clinically euthyroid at the time of the measurements. The mean PBI was 8.3 μg./100 ml. and the mean T₄ was 10.8 μg./100 ml. The range of values for the PBI was 3.5 to 13.2 and for the T₄ was 3.1 to 17.0. Because of the wide range of values, it is considered that the judgement of whether a patient is euthyroid on L-thyroxine therapy should be based primarily on clinical evaluation and only secondarily on serum T₄ or PBI levels.     

Effects of exogenous cortisol and seawater adaptation on thyroid hormone receptors in the smolt stage of the sockeye salmon,Oncorhynchus nerka

The objective of this investigation was to quantify how thyroid hormone receptors of the sockeye salmon, Oncorhynchus nerka, respond to salinity changes from freshwater (FW) to seawater (SW) conditions. Thyroid hormone receptors (TRs) mRNA and protein expressions levels significantly increased when the fish were transferred from FW to SW, and the plasma T₃ and T₄ levels were significantly highest at 50 % SW and then maintained as control. Moreover, these parameters were significantly lower in the cortisol-injected groups than in the control. Hence, TRs, T₃, and T₄ may play a role in SW adaptation, when the fish migrate from FW to SW environments. We showed a negative correlation between cortisol and thyroid hormone levels, and a significant increase in plasma K⁺ levels in the kidney when the fish were transferred to SW, with levels being significantly lower in the cortisol-injected group. Hence, cortisol appears to be a stress hormone, and the plasma Na⁺ and Cl^- levels significantly increased when the fish were transferred to SW, with levels being significantly lower in the cortisol-injected group. These results indicate that cortisol modulates ion transportation in the plasma.     

Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with excessive iodine exposure

The effects of supplementing selenium on thyroid hormone metabolism were studied on mice with excessive iodine exposure. The serum concentrations of thyroxine (T₄) and triiodothyronine (T₃) and the activities of iodothyronine 5′ and 5-deiodinase (D2, D3) were measured in the brain of filial mice to study the influence of selenium on thyroid hormone metabolism. Measurements were carried out on postnatal day 0, 14, and 28. It was found that selenium supplementation alleviated the adverse effects of excessive iodine on progeny. The serum TT₄ level as well as TT₄ and TT₃ concentrations and D3 activity in cerebrum of progeny decreased, whereas D2 activity increased in the cerebrum of progeny on postnatal day 0 and 14. Selenium supplementation exerted some favorable effects on thyroid hormone metabolism in cerebrum of progeny of dam with excessive iodine intake.     

Response of the interrenal to adrenocorticotropic hormone after short-term thyroxine treatment of coho salmon (Oncorhynchus kisutch)

The effects of experimentally elevated plasma thyroxine levels on the subsequent response of interrenals of coho salmon (Oncorhynchus kisutch) to adrenocorticotropic hormone (ACTH) in vitro were examined. Animals were treated with thyroxine by immersion (200 micrograms/L) for 3 days, which resulted in physiological elevations in circulating thyroxine. In animals treated before the parr-smolt transformation was completed (early smolts), thyroxine had no effect on plasma cortisol levels but significantly enhanced the sensitivity of the interrenal to ACTH in vitro. In animals treated after the period of smoltification (postsmolts), plasma cortisol levels were significantly higher than those of controls; both experimental and control animals had plasma cortisol levels higher than normally observed at this stage of development. The response of the interrenals of thyroxine-treated postsmolts to ACTH in vitro was significantly lower than that of controls. Results from the experiments using early smolts are in agreement with studies in other vertebrates showing that thyroid hormones are involved in maintaining the normal functioning of corticosteroidogenic tissue and suggest that thyroid hormones may be involved in the activation of the interrenal that occurs during smoltification. The results obtained using postsmolts are more difficult to interpret because of the possibility that these animals were physiologically stressed by the treatment. Increased ACTH release in vivo resulting from stress may have led to a depression of interrenal sensitivity to ACTH in vitro and may have masked a refractoriness of the pituitary-interrenal axis to thyroxine.     

Alterations in Hypothalamus-Pituitary-Adrenal/Thyroid Axes and Gonadotropin-Releasing Hormone in the Patients with Primary Insomnia: A Clinical Research

The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes’ hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman’s correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the “stepwise” method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.     

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S)

ObjectiveSulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3′-triiodothyronine (T₃) sulfate (T₃S) in rats. The present study investigated whether T₃S is absorbed after oral administration in humans and if it represents a source of T₃.MethodsTwenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T₃) prior to ¹³¹I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T₃S was administered 3 days before the planned administration of ¹³¹I. Blood samples for serum T₃S and total T₃ (TT₃) concentrations were obtained at various times up to 48 hours after T₃S administration.ResultsAt all T₃S doses, serum T₃S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T₃S maximum concentration (C_max) and area under the 0-to 48-hour concentration-time curve (AUC_0-48h) were directly and significantly related to the administered dose. An increase in serum TT₃ concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T₃S administration. There was a significant direct correlation between the TT₃ AUC_0-48h and the administered dose of T₃S. No changes in serum free thyroxine (T₄) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T₃S. No adverse events were reported.Conclusion(1) T₃S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T₃S is converted to T₃ in a dose-dependent manner, resulting in steady-state serum T₃ concentrations for 48 hours; (3) T₃S may represent a new agent in combination with T₄ in the therapy of hypothyroidism, if similar conversion of T₃S to T₃ can be demonstrated in euthyroid patients who are already taking T₄. (Endocr Pract. 2014;20:680-689)     

广泛性焦虑障碍患者人格特征与免疫功能、甲状腺激素和神经内分泌激素的相关性分析

摘要 目的：探讨广泛性焦虑障碍（GAD）患者人格特征与免疫功能、甲状腺激素和神经内分泌激素的相关性。方法：选择2019年1月~2020年12月北部战区空军医院心理科收治的GAD患者80例作为研究组,选择同期于北部战区空军医院体检的健康志愿者80例作为对照组。应用艾森克人格问卷简式量表中国版（EPQ-RSC）对受试者人格特征进行评价,比较两组EPQ-RSC评分结果、血液中CD3⁺、CD4⁺、自然杀伤细胞（NK）比例,血清白细胞介素（IL）-2、IL-6,三碘甲状腺原氨酸（T3）、甲状腺素（T4）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、去甲肾上腺素（NE）、促肾上腺皮质激素（ACTH）、皮质醇（CS）水平,并分析其相关性。结果：研究组精神质（P）、神经质（N）评分及EPQ-RSC总分均显著高于对照组（P<0.05）,研究组CD3⁺、CD4⁺、NK比例显著低于对照组,血清IL-2、IL-6水平显著高于对照组（P<0.05）。研究组血清FT3、FT4水平显著低于对照组（P<0.05）。研究组血清CS水平显著低于对照组,NE、ACTH水平显著高于对照组（P<0.05）。Pearson相关分析显示,GAD患者N、P评分及EPQ-RSC总分与CD3⁺、CD4⁺、NK、FT3、FT4、CS呈负相关（P<0.05）,与IL-2、IL-6、NE、ACTH呈正相关（P<0.05）。结论：GAD患者存在免疫功能损伤、神经内分泌激素和甲状腺激素水平异常,且均与患者P、N倾向的人格特征有关。     

Infantile spasms in children with Down syndrome

Down syndrome (DS) is the most common genetic cause of mental retardation. It is estimated that 5-13% of persons affected by DS have seizures. Infantile spasms are the most common type of seizures and usually are well controlled with steroids and antiepileptic drugs. We present 11 children at the age of 3 years and 4 months to 10 years and 7 months with DS and infantile spasms, treated at Children's Hospital Zagreb from January 2000 until July 2009. Infantile spasms began at the age of 5 to 10.5 months in 10 children, in one child at the age of 16 months. Only one child had perinatal risk factors for the development of IS. Changes in EEG correlated to hypsarrhythmia. Infantile spasms were treated initially with antiepileptic drugs, most often with valproic acid. Treatment was inefficient in 10/11 patients. After application of ACTH, infantile spasms stopped between 7 and 15 days in 6 patients, until 28th day in 4 patients. Hypsarrhythmia vanished in all children. During follow-up period (2 years and 7 months to 9 years and 5 months) none of the children developed another type of seizures. No major epileptogenic changes were registered in EEG. Antiepileptic therapy was discontinued in 4 children (aged 4 years and 2 months to 5 years). In this group is the boy who died of heart failure. Infantile spasms associated with DS are categorized into symptomatic group. The existence of cerebral pathology and delayed psycho-motor development precedes occurrence of seizures. It is possible to achieve good control of seizures and disappearance of hypsarrhythmia with application of ACTH and antiepileptic drugs.     

Active and indolent chronic lymphocytic leukaemia – immune and hormonal peculiarities

 A group of 138 B cell chronic lymphocytic leukaemia (B-CLL) patients, 83 with active disease and 53 having the indolent form of the disease, were evaluated. The aim of the study was to clarify whether indolent and active B-CLL differ in their immune and hormonal characteristics. Peripheral blood lymphocyte proliferation in response to phytohaemagglutinin, concanavalin A, recombinant interleukin-2, dextran sulphate, Pisum sativatum agglutinin and wheat germ agglutinin was investigated. Serum immunoglobulin and β₂ microglobulin levels were determined. Adrenocorticotropic hormone (ACTH), cortisol, follicle-stimulating hormone luteinizing hormone, 17β-oestradiol, testosterone, triiodothyronine, thyroxine, thyroglobulin and thyrotropic hormone levels were determined by radioimmunoassay. Active and indolent CLL presented differences in immunological characteristics, as demonstrated by the more severe suppression of T lymphocyte function, reduced IgA level and considerably higher serum β2-microglobulin values in active disease. Immune disturbances were accompanied by hormonal imbalance, depending on disease status: lower ACTH, cortisol and triiodothyronine levels were established to occur in active CLL compared to indolent disease. Male patients demonstrated striking changes in sex hormones, which were more evident in active disease. The findings point to the complexity of immuno-hormonal disturbances in CLL with differences in the active and indolent state of the disease. Received: 19 June 1997 / Accepted: 14 August 1997     

Hormonal control of growth of the infant rat II. Effects of hypophysectomy,thyroidectomy and the combination of these operations: Evidence that neither TSH nor thyroxine is transferred via milk to suckling young

The relative importance of the pituitary and thyroid glands for growth of infant rats was investigated in experiments which also provided information on the possible role of the milk as a source of thyroxine (T₄) or TSH for suckling pups. Following neonatal hypophysectomy (H) or radiothyroidectomy (RT) body weight gain and skeletal growth (tail growth) were inhibited by about 40% compared to sham H controls. Combined H and T did not inhibit growth any more than either operation alone. Chemical thyroidectomy (CT) by tapazole injections was less effective at inhibiting body weight gain and tail growth than was RT. CT combined with H did not inhibit growth more than H alone.Total serum thyroxine (T₄) levels, as measured by radioimmunoassay, correlated well with the growth occuring following each procedure. H, RT, H plus RT and H plus CT lowered serum T₄ to the limit of sensitivity of the assay (0.5 ug %). CT alone was less effective in lowering serum T₄ levels than was H or RT.These results demonstrate that RT is about as effective as H at inhibiting growth of infant rats. They also show that T of H pups does not further inhibit their growth. Thus, 50–60% of the growth of infant rats is independent of the pup's pituitary and thyroid. Our results also indicate that significant passage of T₄ or TSH from mother to pup via milk does not occur. If TSH were transferred via milk the H pups should have grown more than the T pups. If T₄ were transfered, the plasma level of T₄ should not have been reduced so drastically by T or H. The reduced but steady growth of the H, T or H plus T pups may still be maintained by as yet undefined milk factors, such as tri-iodothyronine or growth factors.