Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in normal subjects and patients with heart failure.

The derangement of neuro-endocrine control of circulation influences both disease evolution and response to treatment in patients with heart failure, but little data are available about the complex relationships between the degree of neuro-hormonal activation and clinical severity. We studied the relationships between cardiac natriuretic hormones (CNHs) and several neuro-hormones and immunological markers in a prospective cohort of 105 consecutive patients with cardiomyopathy (77 men and 28 women, mean age 66.7+/-12.4 years, range 33-89 years). We assayed the circulating levels of CNHs (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)), plasma renin activity (PRA), aldosterone, cortisol, adrenaline, noradrenaline, thyroid hormones and thyroid stimulating hormone (TSH), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The concentrations of all CNHs and neurohormones were higher in patients with heart failure compared to normal subjects, except for free triiodothyronine (FT3), which was below normal values. ANP was positively related to NYHA class, IL-6, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. BNP was positively related to age, NYHA class, IL-6, TNF-alpha, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. A stepwise multiple linear regression indicated that plasma ANP depended only on ejection fraction, adrenaline and noradrenaline values, while for plasma BNP variation NYHA class contributed too. Our data confirm a progressive activation of hormonal and immunological systems in patients with heart failure. Furthermore, CNH circulating levels in heart failure are affected not only by cardiac function and disease severity, but also by activation of neuro-hormonal and stress-related cytokine systems, as well as by the thyroid hormones, even on usual medical treatment.     

Hormonal interactions and glucocorticoid receptors in patients with the nephrotic syndrome]

As many as 27 children aged 6 to 15 years with morphologically verified nephropathies were examined. Four variants of changes in the thyroid status, characteristic of children with different variants of nephrotic syndrome were distinguished: 1) biochemical signs of primary hypothyroidism, 2) biochemical signs of secondary hypothyroidism, 3) low content of T3, 4) dysfunction of the hypophyseal and thyroid system. It is shown that the low level of steroid receptors, thyroid hormones that the low level of steroid receptors, thyroid hormones (T3 and T4) and cortisol is typical of children with the signs of renal dysplasia. It is assumed that superaddition under such conditions of immune glomerulopathy (glomerulonephritis and nephrotic syndrome) gives rise to the resistance to the treatment with glucocorticoids.     

Thyrotropin Response to Synthetic Thyrotropin-Releasing Hormone in Normal Subjects and in Patients with Nontoxic Goiter

Abstract. 400 μg TRH given intravenously to normal subjects produced a peak serum TSH within 20 or 30 min. TSH levels were significantly increased as early as 10 min. after the injection. An oral dose of 10 mg of TRH gave a slower and more sustained response in normal subjects. The magnitude of the TSH response was directly related to the basal serum TSH level and inversely proportional to the basal concentration of blood thyroxine. No alteration in the normal pattern of TSH response was observed in patients with euthyroid nontoxic goiters. The data obtained from the normal subjects indicate that the magnitude of the pituitary response to TRH is closely related to the level of the circulating thyroid hormones. Thus, in patients with thyroid pathology the significance of the TSH response curve to TRH must be interpreted after taking into account the level of circulating thyroid hormones. This is particulary important before drawing conclusions concerning any primary defect of the hypothalamo-pituitary system in thyroid pathology.     

Hormonal changes in brain dead patients

Thirty neurologically impaired (Glasgow Coma Score less than 7) patients were evaluated to determine if changes in serum levels of thyroid hormone, cortisol, insulin, or lactate suggest that replacement therapy is needed before removal of organs for donation. Serum levels of free thyroxine (fT4), thyroid-stimulating hormone (TSH), reverse T3 (rT3), cortisol, insulin, and lactate were monitored in 16 patients before and after brain death and in 14 additional patients who were similarly compromised but did not become brain dead. Low fT3, normal fT4, and normal or high rT3 as found in most patients were consistent with a variant of the euthyroid sick syndrome although TSH was elevated in some patients. Cortisol, insulin, and lactate levels were also normal or high. No correlation was found between low thyroid hormones and elevated lactate or the amount of vasopressor needed to sustain BP. No significant changes occurred in hormone or lactate levels after brain death. The explanation for an elevated lactate remains unclear but we do not believe this single finding justifies the diagnosis of a hypothyroid state in these patients or the administration of thyroid hormone to brain dead organ donors.     

急性心肌梗死患者血清激素水平的变化及其临床意义

本文测定了21例急性心肌梗死（AMI）患者的血清甲状腺激素，胰岛素、胰高糖素、皮质醇、胃泌素和催乳素浓度并与正常对照组相比较，结果发现，AMI患者血清T3明显降低（P＜0．001），并与皮质醇浓度升高有显著的相关性（P＜0．05），T4，TSH无明显变化（P＞0．05）；胰高糖素、胃泌素、催乳素、皮质醇浓度均有意义地升高（P＜0．001），胰岛素无变化（P＞0.05）。有并发症的AMI组与无并发症AMI组两者相比，前者T3更降低（P＜0．01），说明AMI低T3与病变程度的预后有关。这些激素变化的可能机制是AMI在应激状态下机体的防御保护性反应。     

Thyroid hormone resistance

General resistance to the action of thyroid hormones is characterized by increased levels of thyroid hormones and normal thyroid hormone binding proteins but clinical euthyroidism. There is a wide clinical spectrum ranging from patients with congenital goitre and signs of subclinical hypothyroidism to subjects with no physical abnormality. In the most affected patients special physical features have been described. Serum thyrotrophin (TSH) and the response to thyrotrophin releasing hormone (TRH) is mostly normal but may fluctuate being at times elevated and even markedly increased values may be encountered. Studies on lymphocytes and fibroblasts indicate that a decreased affinity of thyroid hormones for nuclear receptors, a decreased binding capacity of the receptors or some post-receptor mechanism may be responsible for these changes. Hitherto, six families, comprising 24 patients and seven single cases, have been described. The pedigrees are compatible with dominant inheritance. Selective refractoriness of the pituitary thyrotrophs to thyroid hormones has been described in five patients with hyperthyroidism. Excessive secretion of TSH is the cause of hyperthyroidism. In four of the cases reported TRH caused an exaggerated TSH response and TSH was partially suppressible by additional exogenous thyroid hormone. The response of TSH and the behaviour of the alpha- and beta-subunits of TSH distinguish this syndrome from TSH-induced hyperthyroidism due to pituitary tumours. The underlying mechanisms are unknown.     

Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.     

Postradiation hypothyroidism in patients with lymphogranulomatosis

A total of 93 patients with Hodgkin's disease were investigated at different times after radiation therapy. The hypothyroid status was found in 21.7% of the patients. The influence of the patients' age at the time of irradiation, administration of iodine-containing contrast drugs, polychemotherapy, and a summary focal dose of thyroid irradiation on the frequency of development of postradiation hypothyrosis was discussed. Criteria for substitution therapy with thyroid hormones were defined.     

Sex differences in the control of plasma concentrations and urinary excretion of glycine betaine in patients attending a lipid disorders clinic

OBJECTIVES: To find whether the control of betaine metabolism differs between male and female patients and identify the effects of insulin and other hormones. DESIGN AND METHODS: Data from non-diabetic lipid clinic patients (82 female symbol and 76 male symbol) were re-analyzed by sex. Data on insulin, thyroid hormones and leptin were included in models to identify factors affecting the circulation and excretion of betaine and its metabolites. RESULTS: Different factors influenced plasma concentrations and urinary excretion of betaine, dimethylglycine and homocysteine in males and females. In males, apolipoprotein B (negative), thyroid stimulating hormone (positive) and insulin (negative) predicted circulating betaine, consistent with betaine-homocysteine methyltransferase mediated control. In females, insulin positively predicted plasma dimethylglycine. Urinary betaine excretion positively predicted circulating homocysteine in males (p<0.001), whereas dimethylglycine excretion (also indicating betaine loss) was a stronger positive predictor (p<0.001) in females. Carnitine affected betaine homeostasis. CONCLUSIONS: Betaine metabolism is under endocrine control, and studies should use sex stratified groups.     

Treatment of migraine with salmon calcitonin: effects on plasma beta-endorphin, ACTH and cortisol levels

In this study we have examined the results of salmon calcitonin treatment on migraine pain. The mechanism by which calcitonin induces analgesia is still not understood. We observed the effect of a 5-day treatment with salmon calcitonin (IM 100 IU/day) on circulating levels of beta-endorphin, ACTH, and cortisol in 20 patients with migraine during the headache-free period. All 3 hormones were increased after the calcitonin administration and the maximum increase was obtained in beta-endorphin levels. There were significant statistical correlations between beta-endorphin, ACTH, and cortisol levels determined before and after calcitonin treatment.     

Perfect storm: Therapeutic plasma exchange for a patient with thyroid storm

Thyroid storm is a potentially lethal complication of hyperthyroidism with increased thyroid hormones and exaggerated symptoms of thyrotoxicosis. First‐line therapy includes methimazole (MMI) or propylthiouracil (PTU) to block production of thyroid hormones as a bridge toward definitive surgical treatment. Untreated thyroid storm has a mortality rate of up to 30%; this is particularly alarming when patients cannot tolerate or fail pharmacotherapy, especially if they cannot undergo thyroidectomy. Therapeutic plasma exchange (TPE) is an ASFA category III indication for thyroid storm, meaning the optimum role of this therapy is not established, and there are a limited number of cases in the literature. Yet TPE can remove T3 and T4 bound to albumin, autoantibodies, catecholamines and cytokines and is likely beneficial for these patients. We report a patient with thyroid storm who could not tolerate PTU, subsequently failed therapy with MMI, and was not appropriate for thyroidectomy. TPE was therefore performed daily for 4 days (1.0 plasma volume with 5% albumin replacement and 2 U of plasma). Over the treatment course, the patient's thyroid hormones normalized and symptoms of thyroid storm largely resolved; his T3 decreased from 2.27 to 0.81 ng/mL (normal 0.8‐2.0), T4 decreased from 4.8 to 1.7 ng/mL (0.8‐1.8), heart rate normalized, altered mental status improved, and he converted to normal sinus rhythm. He was ultimately discharged in euthyroid state. He experienced no side effects from his TPE procedures. TPE is a safe and effective treatment for thyroid storm when conventional treatments are not successful or appropriate.     

Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation.

Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5-6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased. Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol. As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.     

Therapeutic plasma exchange for control of thyroid storm

Therapeutic plasma exchange (TPE) for thyroid storm has recently been upgraded to a category II indication after decades though its recommendation level still remains at Grade 2C according to the American Society for Apheresis (ASFA). In the absence of prospective randomized controlled trials due to the rarity of thyroid storm, retrospective data from case series continue to elevate the clinical evidence supporting TPE as a life‐saving modality for complicated thyroid storm patients. We report three cases of life‐threatening thyroid storm from Graves' disease rescued by TPE via rapid reduction in circulating thyroid hormones. Each patient underwent TPE when it was judged that other thyroid storm treatment options were futile or unsafe. The first patient received 4 cycles of TPE while the second patient received 9 cycles of TPE, and the third patient received 2 cycles of TPE with satisfactory clinical improvement. Plasma FT4 and TSH receptor antibody levels of the first case declined by 41.3% and >50% respectively right after the first round of TPE; plasma FT4 of the second patient dropped by up to 31.6% during the course of TPE; plasma FT4 and TSH receptor antibody of the third patient declined by 66% and 56.2% respectively after the first cycle of TPE. This demonstrates the safety, efficacy, and feasibility of TPE in thyroid storm especially when other therapeutic interventions are contraindicated. TPE operates via the elimination of serum proteins‐bound thyroid hormones, thyroid autoantibodies, cytokines, and catecholamines in addition to increasing unsaturated binding sites for thyroid hormones.     

Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study.

Hyperthyroidism is associated with reduced bone mineral density. Conflicting data exist regarding the effects of thyroxine therapy on bone metabolism. The aim of the present study was to assess changes in markers of bone turnover in thyroid dysfunction. A total of 28 patients with overt hyperthyroidism, eight patients with suppressed TSH levels (thyroid hormones within the euthyroid range, no T4 therapy), 25 euthyroid and four hypothyroid patients were included in the present study. Hyperthyroidism resulted in increased bone metabolism, as reflected by increased bone resorption and bone formation parameters. No significant differences in mean levels between patients with TSH supression and those with euthyroidism could be observed; however, a higher frequency of elevated urinary PYD- and DPD excretion rates were noted in patients with TSH suppression. Regression analysis revealed highly significant correlations between bone resorption markers and thyroid parameters, suggesting, that even a mild thyroid hormone excess may lead to an increase in bone resorption. In subjects with suppressed TSH levels and peripheral thyroid hormone levels within the euthyroid range, elevated bone resorption markers point to subclinical hyperthyroidism, if other reasons for an increase in bone turnover rates can be excluded.     

Power Doppler ultrasonographic assistance in percutaneous ethanol injection of autonomously functioning thyroid nodules.

The purpose of this study was to explore the potential role of power Doppler sonography in guiding percutaneous ethanol injection of autonomously functioning thyroid nodules. Thirty-two patients with pretoxic adenoma and 15 with toxic adenoma underwent percutaneous ethanol injection under power Doppler sonographic guidance. All patients with pretoxic adenoma and 13 of 15 patients with toxic adenoma were treated successfully (normalization of circulating thyroid hormones and thyroid stimulating hormone levels and disappearance of nodular hyperactivity with complete recovery of extranodular tracer uptake at scintigraphy). Power Doppler sonography showed the progressive reduction of the intranodular blood flow until its extinction after 6 to 12 months. Nodular shrinkage was obtained in all patients (from 10.85 +/-1.04 to 2.9 +/- 0.3 ml in pretoxic adenoma and from 15.4 +/- 1.8 to 4.2 +/- 0.7 ml in toxic adenoma. Power Doppler sonographic guidance seems to improve the outcome of percutaneous ethanol injection, allowing detection of blood flow even in very small vessels, permitting the ethanol to be guided toward the main afferent vessels of the nodules, and making it possible to monitor the diffusion and the effects of ethanol on nodular vascularization.     

Functional state of the neuroendocrine system in men after myocardial infarction in the period of rehabilitation

The paper is devoted to systemic analysis of changes of the hypophyseal hormones, sex and adrenal glands, and thyroid in men in the course of a year after MI. A stable state of the hypophyseal-gonadal system the first 2 mos after MI was followed by a significant decrease in prolactin, testosterone levels and an increase in estradiol concentration. A marked decrease in STH, cortisol, TSH and thyroid hormone levels, and monotonously decreased ("leveled") circadian rhythm of secretion of practically all hormones were revealed. Functional exercise tests have shown switching over of the neuroendocrine system of MI patients to a special sparing regimen functioning at a qualitatively new hormonal-metabolic level rather than its depletion.     

Hormonal responses to trauma.

OBJECTIVES: To review the hormonal changes that have been reported after trauma, to define their etiologies, and to describe their consequences. DATA SOURCES: Literature review using MEDLINE and original data. DATA SYNTHESIS: Hormonal responses to trauma are bidirectional. Functional derangements include increases in adrenocorticotropin hormone and cortisol, growth hormone, and prolactin levels. In contrast, gonadotropin and gonadal steroid, and thyroid hormone concentrations decrease. The response is immediate but not necessarily sustained for those hormones that respond with increased secretion, whereas the effect may not become apparent for several hours, may be maximal after 1 to 4 days, and may persist for the duration of illness for those hormones that decrease. The reduction in hormone concentrations generally reflect diminished secretion, with the exception of the thyroid hormones where altered metabolic pathways and enhanced metabolic clearance play a major role. CONCLUSIONS: The changes in circulating levels do not appear to be injury specific, but tend to reflect the severity of the traumatic insult, and there are some data for cortisol and thyroxine that show their concentrations may be of predictive value. In head-injured patients, structural as well as functional pituitary changes may be present. Patients may show varying degrees of pituitary insufficiency. However, the presence of hyperprolactinemia strongly suggests involvement of the hypothalamus. With the exception of bonafide hypopituitarism, the relevance of the hormonal changes after trauma awaits clarification.     

Influence of thyroid hormone status on mevalonate metabolism in rats.

Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to cholesterol or, by the shunt pathway, to CO2. Previous investigations have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism and that sex hormones as well as insulin markedly influence circulating mevalonate metabolism. The present study examined in rats the influence of thyroid hormone status on mevalonate metabolism in vivo and in vitro. L-thyroxine administration increased renal conversion of circulating mevalonate to cholesterol, 41% in the females and 22% in the males. Conversely, hypothyroidism induced by 6 N propyl-2-thiouracil reduced renal conversion of circulatng mevalonate to cholesterol by 45% in females and 27% in males; thyroid hormone replacement in these animals returned cholesterogenesis in the kidneys to supranormal levels. Neither L-thyroxine nor hypothyroidism altered circulating mevalonate conversion to cholesterol in the liver or carcass. In vitro studies confirmed the in vivo observations. Changes in thyroid hormone produced only minor changes in the shunt pathway of mevalonate metabolism. This study demonstrates that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of mevalonate to cholesterol, an effect localized solely to the kidneys.     

Successful preoperative treatment of a Graves' disease patient with agranulocytosis and hemophagocytosis using double filtration plasmapheresis

Agranulocytosis is an uncommon but serious complication of Graves' disease under thionamide therapy. In some patients removal of circulating thyroid hormones and thyroid antibodies by plasmapheresis is an effective adjunctive therapeutic option. In perioperative settings, however, plasmapheresis may cause excess bleeding intraoperatively due to coagulation factor depletion unless fresh frozen plasma (FFP) products are used in the replacement fluid mix. Double filtration plasmapheresis (DFPP) in which only a small amount of albumin supplementation is used may be a potential alternative to conventional apheresis interventions where clotting factor depletion is problematic. We report a case of a patient with Graves' disease complicated with intravenous immunoglobulin responsive methimazole-induced agranulocytosis/hemophagocytosis who underwent successful preoperative DFPP treatment in preparation for thyriodectomy. In addition to conventional apheresis using FFP replacement, DFPP may offer an effective adjunct option in the management of hyperthyroid patients needing emergent surgical interventions.     

Thyroid hormone regulates ontogeny of beta adrenergic receptors and adenylate cyclase in rat heart and kidney: effects of propylthiouracil-induced perinatal hypothyroidism.

In mature animals, thyroid hormone is permissive for beta adrenergic receptor expression and adrenergic control of adenylate cyclase. To determine if endogenous thyroid hormones play a similar role in the development of receptors and transduction mechanisms, we administered propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5. Circulating thyroid hormones were completely suppressed through postnatal day 10 and then rose to only slightly subnormal values by the 3rd to 4th postnatal week. In the heart, hypothyroidism completely suppressed the initial development of beta adrenergic receptor binding sites, with recovery paralleling the return of thyroid hormone levels. In contrast, development of basal and isoproterenol-stimulated adenylate cyclase activity showed more lasting deficiencies with a delayed onset corresponding to general growth impairment; however, forskolin-stimulated adenylate cyclase developed in a nearly normal pattern. Effects on development of renal beta receptors and adenylate cyclase were of smaller magnitude and comprised only the delayed onset phase; receptor deficiencies appeared after 10 days and adverse effects on adenylate cyclase were limited to the isoproterenol-sensitive component, consisting of a shift of the ontogenetic peak to later ages. Endogenous thyroid hormones thus contribute two distinct factors to beta receptor/adenylate cyclase development: they are obligatory for cardiac beta receptor development, but also, in parallel with general effects on growth and development, serve to program the ontogeny of transduction factors linking the receptors to adenylate cyclase. The predominance of propylthiouracil effects on isoproterenol-stimulated adenylate cyclase but not on enzymatic responses to forskolin suggests that thyroid hormones may be controlling the development of regulatory G-proteins.