Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review.

Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.

Diagnosis and treatment of low T3 syndrome in neurocritical patients.

WHAT IS KNOWN AND OBJECTIVE: Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T3 syndrome remains controversial. We studied the role of low T3 state as a predictor of outcomes in neurocritical patients and examined the effect of HRT on prognosis. METHODS: A retrospective analysis was performed on the data of 32 neurocritical patients with low T3 syndrome who were admitted to the neuro-intensive care unit of Peking Union Medical College Hospital between January 2012 and October 2018. While 18/32 (56.25%) patients received HRT (HRT group; n = 18), 14/32 (43.75%) patients did not receive HRT (non-HRT group; n = 14). Patients were followed up for periods ranging from 3 months to 72 months. Baseline clinical and laboratory data were compared between the two groups using Mann-Whitney U tests or the t tests. Overall survival was assessed by Kaplan-Meier curve and compared by log-rank tests. Univariate and multivariate regression analyses were performed to identify the factors associated with prognosis and estimate the effect of HRT. We also assessed the influence of HRT on final neurological function, using the Glasgow Coma Scale (GCS) and the Glasgow Outcome Scale (GOS) scores. RESULTS AND DISCUSSION: The neurocritical events in our cohort included post-operative complications (n = 18), traumatic brain injury (n = 8) and spontaneous intracerebral haemorrhage (n = 6). Mean GCS score in the cohort was 6.41 (6.44 ± 3.14 in HRT group vs 6.36 ± 2.06 in non-HRT group). A total of 15/32 (46.87%) deaths were recorded (7 in the HRT group, 8 in the non-HRT group). In the HRT group, 15 patients underwent repeat thyroid function tests after completion of HRT; the low T3 situation was corrected in only 5/15 (33.3%) patients. Overall survival was significantly shorter in the non-HRT group than in the HRT group (16.45 months vs 47.47 months; P = .034). In univariate regression analysis, the HRT group has the lower mortality risk than the non-HRT group (HR = 0.301, 95% Cl: 0.094-0.964; P = .043). However, multivariate regression analysis showed no significant difference in mortality risk between the two groups (HR = 0.340 95% CI: 0.099-1.172; P = .087). There was no significant difference in effects of HRT on the short- and long-term neurological function between the groups. WHAT IS NEW AND CONCLUSION: Low T3 syndrome may influence the prognosis of neurocritical patients, attention should be paid to the changes in serum T3 levels during treatment. Although it is unclear to what extent HRT can improve the short or long-term outcomes of neurological function, it can significantly improve the survival rates of neurocritical patients.

The Role of Thyroid Hormones in Heart Failure.

Cardiovascular diseases are the leading cause of death worldwide. Heart failure is the terminal manifestation of cardiovascular diseases, and its morbidity and mortality remain high. The prevalence of heart failure with preserved ejection fraction (HFpEF) among heart failure patients remains uncertain. However, recent studies have found that it ranged from 40 to 71%. There is still no effective treatment for HFpEF. Thyroid hormones (TH) have central regulatory actions in the cardiovascular system, particularly in the heart. Changes in plasmatic or tissue thyroid hormone levels are associated with significant alterations in cardiovascular function. A significant proportion of patients with heart failure presents some form of thyroid dysfunction including hypothyroidism, hyperthyroidism, and low T3 syndrome. Furthermore, thyroid hormones can vary at a local level independently of the serum TH levels. This may lead to local cardiac hypothyroidism in heart failure. Based on these findings and the role that TH play in cardiovascular regulation, they were proposed as a potential target for heart failure therapy. Several clinical and experimental studies have shown beneficial effects of TH supplementation. Data from epidemiological studies supports a higher risk of heart failure and a worse prognosis in heart failure patients with low levels of TH. In addition, animal studies and small clinical studies suggest that TH supplementation may improve cardiac function in heart failure. Although further studies are needed to evaluate the safety and efficacy of TH in this context, the available evidence suggests that TH modulation is a promising therapeutic approach to heart failure.

Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats.

BACKGROUND: The roles of antioxidant therapy on non-thyroidal illness syndrome (NTIS) in uremic rats is still unclear. MATERIALS AND METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into blank, 5/6 nephrectomy (Nx), pyrrolidine dithiocarbamate (PDTC, 10 mg/100 g), sodium bicarbonate (SB, 0.1 g/100 g), N-acetylcysteine (NAC, 80 mg/100 g) and thyroid hormones (TH, levothyroxine 2 µg/100 g) groups. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), interleukin (IL)-1ß, free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were detected in the sixth week. The expressions of IL-1ß and deiodinase type 1 (DIO1) were assessed by western blotting. The nuclear factor kappa B (NF-κB) inflammatory signal pathway was confirmed by electrophoretic mobility shift assay (EMSA). RESULTS: Compared with 5/6 Nx group, PDTC and NAC significantly reduced the levels (p < 0.01, respectively) of serum MDA, AOPP, TSH, and elevated levels of serum SOD (p < 0.01, respectively) and FT3 (p = 0.016 and p < 0.01). Neither had significant effects on serum IL-1ß content (p = 0.612 and p = 0.582). PDTC and NAC markedly decreased the protein expression of IL-1ß (p < 0.01) and increased the protein expression of DIO1 (p < 0.01), respectively. Both had been considerably blunted NF-κB activity (p < 0.01). CONCLUSIONS: In uremic rat model, PDTC and NAC can effectively improve oxidative stress level and NTIS. In terms of improving oxidative stress level, NAC is probably superior to PDTC.

Emerging pharmacotherapy for treatment of traumatic brain injury: targeting hypopituitarism and inflammation.

INTRODUCTION: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the developed world. In particular, TBI is an important cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. AREAS COVERED: There is a large body of evidence that suggest that TBI conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90%. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in TBI conditions. EXPERT OPINION: The aim of this paper is to review the history and pathophysiology of TBI and to summarize the best evidence of TBI as a cause of pituitary deficiency. Moreover, in this article we will describe the multiple changes which occur within the hypothalamic-pituitary-thyroid axis in critical illness, giving rise to 'sick euthyroid syndrome', focus our attention on thyroid hormones circulating levels from the initial insult to critical illness.

An update for the controversies and hypotheses of regulating nonthyroidal illness syndrome in chronic kidney diseases.

Nonthyroidal illness syndrome (NTIS) is widely found in the patients with chronic kidney disease (CKD) or critical illness. However, the exact pathogenesis and reasonable treatment remain unclear. To identify suitable studies for inclusion in present review, a search for articles using PubMed search engine with combined terms: (thyroid OR hypothyroidism OR hyperthyroidism OR triiodothyronine) AND (glomerulonephritis OR chronic kidney disease OR chronic renal failure OR end stage renal disease OR hemodialysis OR peritoneal dialysis OR kidney transplantation OR renal transplantation) was performed. The bibliographies of relevant articles were also hand searched. The search was updated on November 8, 2013. Mechanisms for the alternations of thyroid hormone concentrations in NTIS are complicated. Inflammatory cytokines and oxidative stress may play pivotal roles in the pathogenesis of NTIS in patients with CKD. It was controversial whether CKD patients with NTIS should be treated with thyroid hormone replacement. N-Acetyl cysteine or sodium bicarbonate may negatively regulate the progress of micro-inflammation in CKD. Large-scale, multi-centered randomized controlled trials should be conducted to verify the NTIS hypothesis in CKD patients.

Thyroid hormone replacement for nephrotic syndrome patients with euthyroid sick syndrome: a meta-analysis.

OBJECTIVE: To assess the efficacy of thyroid hormone replacement therapy for nephrotic syndrome (NS) patients associated with euthyroid sick syndrome (ESS). MATERIALS AND METHODS: The Cochrane library, ISI, Ovid, PubMed, Chinese Biomedicine Database were searched, and reference list of relevant articles were selected. Randomized controlled trials (RCTs) or quasi-RCTs with thyroid hormone replacement on NS patients associated with ESS were included in this analysis. RESULTS: Six trials (329 participants) were included. Meta-analysis showed that thyroid hormone replacement therapy can significantly increase the completely remission rate [OR = 3.04, 95% confidence interval (CI): 3.04-1.88, p < 0.00001] and total response rate (OR = 4.63, 95% CI: 2.46-8.71, p < 0.00001) of NS patients associated with ESS. No side effect was observed during the follow-up period. There was no obvious publication bias in the mete-analysis studies. CONCLUSIONS: Thyroid hormone replacement therapy significantly increases the remission of ESS in patients with NS.

[The incidence of hypothyroidism symptoms and risk factors for cardiovascular events in subclinical hypothyroidism]. / Czestosc wystepowania objawów niedoczynnosci tarczycy oraz czynników ryzyka sercowo-naczyniowego w subklinicznej niedoczynnosci tarczycy.

UNLABELLED: The clinical significance of subclinical hypothyroidism (SH) has not been determined. There are different opinions with regard to symptoms and clinical consequences of SH as well as effectiveness of treatment. Aim of study was the analysis of incidence of hypothyroidism symptoms and selected cardiovascular risk factors in patients with SH in comparison to euthyroid individuals and the evaluation of the effect of treatment of SH on the above parameters. MATERIALS AND METHODS: Fifty patients were included in the study: 25 with SH, 25 in euthyreosis (C). The incidence of hypothyroidism symptoms and metabolic syndrome (MS), as well as total cholesterol (TCH), LDL, HDL triglycerides (TGL), glucose levels, values of systolic (SBP) and diastolic (DBP) blood pressure and the relationship between these factors and laboratory indexes of SH intensity were analyzed. Moreover, the risk of cardiovascular mortality (RCM) with the application of the HeartSCORE Risk Chart was evaluated. After a period of six months a similar analysis in the SH group was conducted; all the patients were administered L-thyroxin (mean dose +/- SD: 67.5 +/- 32.1 microg). RESULTS: The mean number of hypothyroidism symptoms was higher in SH than in C group (SH: 8.4 +/- 3.2 vs. C: 1.7 +/- 1.5, p < 0.0005). Normalization of TSH observed in 17 patients resulted in a decrease in the mean number of symptoms (9.1 +/- 2.8 vs. 5.9 +/- 2.9, p < 0.0001). There were not differences between groups in the incidence of the MS and MS components and also the RCM. However only in SH group a positive correlations between TSH and BMI, TSH and age, age and TCH and LDL levels and SBP DBP values and also between TSH and the RCM were noted. Normalization of TSH level resulted in a decrease in the RCM (p = 0.055). CONCLUSIONS: Treatment of SH might bring potential benefits; it might lessen symptoms and reduce the risk of cardiovascular mortality.

Triiodothyronine hormone supplementation therapy in septic shock patients with euthyroid sick syndrome: two pilot, placebo-controlled, randomized trials.

BACKGROUND: To assess 28-day survival in two pilot groups of septic shock patients with euthyroid sick syndrome (ESS) supplemented with triiodothyronine (T3). METHODS: A total of 95 septic shock patients with ESS were divided according to values of the thyroid hormones into low T3 and low T3T4 groups. Among 48 patients with low T3, 24 (50%) were randomized to T3 for 4 days and 24 (50%) to placebo. Among 47 patients with low T3T4, 24 (51%) were randomized to T3 for 4 days and 23 (49%) to placebo. The analysis included 28-day survival as the primary outcome and laboratory with hemodynamics as the secondary outcomes. Laboratory data were analyzed on the day of admission (T0), on the first (T1), third (T2) and seventh day (T3) with hemodynamics analyzed for the first four days. RESULTS: In the low T3 population, 18 (75%) patients receiving T3 died at day 28 compared with 8 (33.3%) patients receiving placebo (p = 0.004). In the low T3T4 population, 6 (25%) patients receiving T3 died in ICU compared with 12 (52.1%) patients receiving placebo (p = 0.039). Oral T3 treatment increased mean arterial pressure values at day 1, day 3 and day 7 in the low T3T4 population, (p = 0.015, =0.005 and =0.042 respectively), and had no significant effect on these values in the low T3 population. CONCLUSION: T3 supplementation was associated with a low 28-day mortality rate in patients with low T3T4 but with increased mortality in patients with low T3 ESS. These results suggest caution before initiating thyroid supplementation in septic patients. REGISTRATION: ClinTrials.gov (NCT05270798).

Disorders in the secretory cycle of follicular thyrocytes and their correction with thyrotropic hormone in experimental non-thyroidal illness syndrome.

The influence of LPS on the thyroid gland leads to more intensive synthesis and release of thyroglobulin into the follicle lumen and inhibition of its resorption and proteolysis, which reduces the production of thyroxine. Treatment with thyroid-stimulating hormone normalizing the secretory processes in the follicular thyrocytes is a pathogenetically justified method for correction of non-thyroidal illness syndrome in acute endotoxicosis.

Thyroid Hormone Supplementation and All-Cause Mortality in Community-Dwelling Older Adults: Results from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful. OBJECTIVES: Determine the association between all-cause mortality and levothyroxine use among older adults. DESIGN: Longitudinal observational study. SETTING: Baltimore Longitudinal Study of Aging. PARTICIPANTS: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up. MEASUREMENTS: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638). RESULTS: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98). CONCLUSION: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults.

Thyroid Hormones in Critical Illness.

Thyroid hormone is integral for normal function, yet during illness, circulating levels of the most active form (triiodothyronine [T3]) decline. Whether this is an adaptive response in critical illness or contributes to progressive disease has remained controversial. This review outlines the basis of thyroid hormone changes during critical illness and considers the evidence regarding T3 replacement.

Therapy with L-thyroxine and Omnadren after Cardiac Surgery. A Case Report.

BACKGROUND: Cardiopulmonary bypass in cardiac surgery produces systemic inflammatory response and catabolic state. Severe stress frequently causes abnormalities in thyroid hormones in the absence of primary thyroid disease, defined as sick euthyroid syndrome (SES). MATERIALS AND METHODS: Supplementation therapy with thyroid and anabolic hormones in combination with an adequate nutritional support has been used to improve outcome in critically ill patient after cardiac surgery. RESULTS: Administration of thyroid and anabolic hormones significantly improved patient's condition. CONCLUSIONS: Supplementation therapy with thyroid and anabolic hormones in combination with an adequate nutritional support could be used to improve hemodynamics, achieve transition to anabolic metabolism and enhance recovery, which could eventually help for a reduction in post-operative morbidity and mortality.

Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study.

CONTEXT: Low-T(3) syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T(3) replacement therapy in patients with low-T(3) syndrome and ischemic or nonischemic dilated cardiomyopathy (DC). DESIGN: A total of 20 clinically stable patients with ischemic (n = 12) or nonischemic (n = 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66-77; median, 25-75th percentile) who underwent 3-d synthetic L-T(3) infusion (study group); the other 10 patients (average age 68 yr, range 64-71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T(3) (initial dose: 20 microg/m(2) body surface.d) or placebo infusion. RESULTS: After T(3) administration, free T(3) concentrations increased until reaching a plateau at 24-48 h (3.43, 3.20-3.84 vs. 1.74, 1.62-1.93 pg/ml; P = 0.03) without side effects. Heart rate decreased significantly after T(3) infusion (63, 60-66 vs. 69, 60-76 beats per minute; P = 0.008). Plasma noradrenaline (347; 270-740 vs. 717, 413-808 pg/ml; P = 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P = 0.02), and aldosterone (175, 152-229 vs. 231, 154-324 pg/ml; P = 0.047) significantly decreased after T(3) administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T(3) administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114-158 ml/m(2) body surface; P = 0.02) and stroke volume (40, 34-44 vs. 35, 28-39 ml/m(2) body surface; P = 0.01) increased, whereas external and intracardiac workload did not change. CONCLUSIONS: In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T(3) administration.

Recent considerations in the treatment of hypothyroidism.

Thyroid hormone deficiency has been recognized and treated with various forms of thyroid hormone replacement over the last century. Since the 1950s, synthetic L-thyroxine has been the therapy of choice. However, there is now recognition that the currently available regimens for the treatment of hypothyroidism may not adequately address the needs of all patients. This review summarizes recent considerations in the field of thyroidology to address the potential for improvement in the treatment of patients. The goal of these improvements should be to achieve both clinical and chemical euthyroidism.

Hyperthyroidism-associated coronary vasospasm with myocardial infarction and subsequent euthyroid angina.

A 40-year-old African-American woman presented with atypical chest pain, an acute non-ST segment elevation myocardial infarction, and angiographic evidence for severe ostial vasospasm of the left main and right coronary arteries. Subsequently, she was diagnosed with hyperthyroidism and treated with antithyroid therapy and oral nitrates. Repeat angiography revealed resolution of the vasospasm; however, the chest pain recurred in the euthyroid state. Hyperthyroidism-associated coronary vasospasm is a rare disorder that characteristically causes angina in young Asian women and resolves with correction of hyperthyroidism. We present an atypical case of an African-American woman presenting with a myocardial infarction who developed recurrent angina while euthyroid.

The nonthyroidal illness syndrome.

This article briefly summarizes thyroid function alterations generally seen in the euthyroid sick syndrome, provides an overview of specific thyroidal adaptations during several clinical conditions and secondary to specific pharmacologic agents, and discusses the current controversy in thyroid hormone treatment of nonthyroidal illness.

Hormonal supplementation in endocrine dysfunction in critically ill patients.

One of the greatest challenges for a physician is a critically ill patient. Regardless of the reason for an admission to the Intensive Care Units (ICU) (e.g. myocardial infarction, severe pneumonia, trauma or many others) each of the above-mentioned conditions impairs homeostasis including instability of the endocrine system. The observed alterations in serum glucose level or clinical signs of hormonal imbalance alarm practitioners and prompt them to an intervention. However, side-effects of administered drugs have to be always considered, because every intervention in the endocrine system may have various consequences or prove itself maleficent. Since critical condition causes numerous changes in the hormonal system, the definition of endocrine gland failure in the ICU patients should differ from the definition related to the general population. This review is aimed at describing alterations, diagnosis and treatment options for an impaired carbohydrate metabolism and inadequate response of the adrenal and thyroid endocrine axis. It has been written in order to aid the choice between "the watch and wait strategy" and aggressive pharmacological intervention. Furthermore, several standard and innovative therapeutic procedures were described and, if possible, compared. Recent articles have been included in order to show current views on the up-to-date clinical approach.

Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease: a single-blind controlled study.

AIM: Non-thyroidal illness syndrome (NTIS) is common among patients with advanced chronic kidney disease (CKD) and is strongly associated with poor prognosis. However, it remains unclear in how to correct this disorder and this study aimed to evaluate the effectiveness of sodium bicarbonate (SB) and N-acetyl-cysteine (NAC) for correcting NTIS status. METHODS: Patients with CKD stage 3-4 were single-blind, placebo-controlled treated with placebo, SB, or NAC for 18 weeks. The primary end points were the correction of NTIS and the occurrence of end-stage renal disease (ESRD). The secondary point was the change in estimated glomerular filtration rate (eGFR) after the follow-up. RESULTS: The Kaplan-Meier survival analysis showed significant lower correcting ratio of NTIS in control group compared with SB group [Hazard ratio (HR) 0.19, 95 % confidence interval (CI) 0.04-0.89, p = 0.035] and NAC group (HR 0.09, 95 % CI 0.02-0.38, p = 0.001), and increased ESRD risk in control group than in SB group (HR 1.97, 95 % CI 1.02-3.84, p = 0.045) and NAC group (HR 5.50, 95 % CI 2.23-13.57, p < 0.001). The Cox regression analysis demonstrated significantly different effectiveness of placebo, SB and NAC on NTIS correction and ESRD risk, p < 0.05, respectively. Variance analysis displayed a greater reduction in eGFR in controls than in SB (p = 0.044) and NAC group (p < 0.001). CONCLUSION: SB and NAC are effective in promoting the recovery from NTIS status and delaying the deterioration of renal function in advanced CKD patients.

Thyroid hormone and insulin-like growth factor-I in patients with multiple myeloma treated with melphalan and prednisone.

BACKGROUND: The relationship between endocrine regulation and immune system has recently become the subject of intense investigations. The aim of this study was the comparative assessment of serum levels of selected hormones and insulin-like growth factor-I (IGF-I) in patients with multiple myeloma (MM) during applied therapy. METHODS: The levels of prolactin, hGH, TSH, fT3, fT4 and IGF-I in serum of 13 untreated patients with MM and in 16 healthy controls were determined. The patients were treated in cyclic courses with melphalan plus prednisone, and investigations were carried out in the first four courses of this therapy. The results were compared in the following manner: (1) at entry between studied MM group and healthy subjects, and (2) during the therapy intragroup-intracyclic comparisons were made in paired serum samples collected from patients before and after every therapeutic course. RESULTS: At entry, significantly lower levels of TSH and fT3 were obtained in MM patients. The means remained within low normal reference range. Slightly increasing levels of TSH and fT3 during treatment with lower concentrations of these hormones after every therapeutic course and a statistically significant difference of fT3 level in the fourth therapy course were revealed. The levels of fT4 were within the normal reference values and showed a tendency to decrease during therapy with significant differences in the first therapeutic course. After the third and the fourth therapy courses, concentrations of IGF-I were statistically significantly higher than initially. CONCLUSIONS: Euthyroid sick syndrome can exist in MM patients, and the therapy with melphalan plus prednisone is accompanied by slightly expressed serum changes of thyroid hormone concentrations and IGF-I levels.