Practical Guidelines for Diagnosing and Treating Thyroid Disease Based on the WOMED Metabolic Model of Disease Focusing on Glycolysis and Coenzyme Q10 Deficiency-A Clinical Alternative to the 2021 Retired Clinical Practice Guidelines of the Endocrine Society.

This review aims to provide a functional, metabolic view of the pathogenesis of benign thyroid disease. Here, we summarize the features of our previous publications on the "WOMED model of benign thyroid disease". As of 2021, the current state of art indicates that the basic alteration in benign thyroid disease is a metabolic switch to glycolysis, which can be recognized using 3D-power Doppler ultrasound. A specific perfusion pattern showing enlarged vessels can be found using this technology. This switch originates from an altered function of Complex I due to acquired coenzyme Q10 deficiency, which leads to a glycolytic state of metabolism together with increased angiogenesis. Implementing a combined supplementation strategy that includes magnesium, selenium, and CoQ10, the morphological and perfusion changes of the thyroid can be reverted, i.e., the metabolic state returns to oxidative phosphorylation. Normalization of iron levels when ferritin is lower than 50 ng/mL is also imperative. We propose that a modern investigation of probable thyroid disease requires the use of 3D-power Doppler sonography to recognize the true metabolic situation of the gland. Blood levels of magnesium, selenium, CoQ10, and ferritin should be monitored. Thyroid function tests are complementary so that hypo- or hyperthyroidism can be recognized. Single TSH determinations do not reflect the glycolytic state.

Implications of Standardized Uptake Values of Oral Squamous Cell Carcinoma in PET-CT on Prognosis, Tumor Characteristics and Mitochondrial DNA Heteroplasmy.

Under aerobic conditions, some cancers switch to glycolysis to cover their energy requirements. Taking advantage of this process, functional imaging techniques such as PET-CT can be used to detect and assess tumorous tissues. The aim of this study was to investigate standardized uptake values and mitochondrial DNA mutations in oral squamous cell carcinoma. A cohort of 57 patients underwent 18[F]FDG-PET-CT and standardized uptake values were collected. In 15 patients, data on mitochondrial DNA mutations of the tumor were available. Kaplan-Meier curves were calculated, and correlation analyses as well as univariate Cox proportional hazard models were performed. Using ROC analysis to determine a statistical threshold for SUVmax in PET investigations, a cut-off value was determined at 9.765 MB/mL. Survival analysis for SUVmax in these groups showed a Hazard Ratio of 4 (95% CI 1.7-9) in the high SUVmax group with 5-year survival rates of 23.5% (p = 0.00042). For SUVmax and clinicopathological tumor features, significant correlations were found. A tendency towards higher mtDNA heteroplasmy levels in high SUVmax groups could be observed. We were able to confirm the prognostic value of SUVmax in OSCC, showing higher survival rates at lower SUVmax levels. Correlations between SUVmax and distinct tumor characteristics were highly significant, providing evidence that SUVmax may act as a reliable diagnostic parameter. Correlation analysis of mtDNA mutations suggests an influence on metabolic activity in OSCC.

Applying a systems approach to thyroid physiology: Looking at the whole with a mitochondrial perspective instead of judging single TSH values or why we should know more about mitochondria to understand metabolism.

Classical thinking in endocrine physiology squeezes our diagnostic handling into a simple negative feedback mechanism with a controller and a controlled variable. In the case of the thyroid this is reduced to TSH and fT3 and fT4, respectively. The setting of this tight notion has no free space for any additions. In this paper we want to challenge this model of limited application by proposing a construct based on a systems approach departing from two basic considerations. In first place since the majority of cases of thyroid disease develop and appear during life it has to be considered as an acquired condition. In the second place, our experience with the reversibility of morphological changes makes the autoimmune theory inconsistent. While medical complexity can expand into the era of OMICS as well as into one where manipulations with the use of knock-outs and -ins are common in science, we have preferred to maintain a simple and practical approach. We will describe the interactions of iron, magnesium, zinc, selenium and coenzyme Q10 with the thyroid axis. The discourse will be then brought into the context of ovarian function, i.e. steroid hormone production. Finally the same elemental players will be presented in relation to the basic mitochondrial machinery that supports the endocrine. We propose that an intact mitochondrial function can guard the normal endocrine function of both the thyroid as well as of the ovarian axis. The basic elements required for this function appear to be magnesium and iron. In the case of the thyroid, magnesium-ATP acts in iodine uptake and the heme protein peroxidase in thyroid hormone synthesis. A similar biochemical process is found in steroid synthesis with cholesterol uptake being the initial energy-dependent step and later the heme protein ferredoxin 1 which is required for steroid synthesis. Magnesium plays a central role in determining the clinical picture associated with thyroid disease and is also involved in maintaining fertility. With the aid of 3D sonography patients needing selenium and/or coenzyme Q10 can be easily identified. By this we firmly believe that physicians should know more about basic biochemistry and the way it fits into mitochondrial function in order to understand metabolism. Contemplating only TSH is highly reductionistic. OUTLINE: •Author's profiles and motivation for this analysis•The philosophical alternatives in science and medicine•Reductionism vs. systems approach in clinical thyroid disease guidelines•The entry into complexity: the involvement of the musculoskeletal system•Integrating East and West: teachings from Chinese Medicine and from evidence based medicine (EBM)•Can a mathematical model represent complexity in the daily thyroid practice?•How effective is thyroxine treatment?•Resolving the situation of residual symptoms in treated patients with thyroid disease•Importance of iron, zinc and magnesium in relation to thyroid function•Putting together new concepts related to thyroid function for a systems approach•Expanding our model into general aspects of medicine.

A post-publication analysis of the idealized upper reference value of 2.5 mIU/L for TSH: Time to support the thyroid axis with magnesium and iron especially in the setting of reproduction medicine.

Laboratory medicine approaches the evaluation of thyroid function mostly through the single determination of the blood level of thyroid stimulating hormone (TSH). Some authors have suggested an upper reference value for TSH of 2.5 mIU/L. This suggestion has not been confirmed by recent clinical studies. These studies have delivered a clinically valid reference range going from 0.3 to 3.5 mIU/L. These values are valid for both for the general population as well as in the setting of fertility and pregnancy. Current biochemical evidence about the elements required to maintain thyroid function shows that these not only include dietary iodine but also magnesium, iron, selenium and coenzyme Q10. Iron is important for the synthesis of thyroid peroxidase; magnesium-ATP contributes to the active process of iodine uptake; iodine has to be sufficiently present in the diet; selenium acts through selenoproteins to protect the thyroid cell during hormone synthesis and in deiodination of thyroxine; coenzyme Q10 influences thyroid vascularity. As a consequence, good clinical practice requires additional biochemical information on the blood levels of magnesium, selenium, coenzyme Q10 as well as iron status. Since these elements are also important for the maintenance of reproductive function, we postulate that they constitute the connecting link between both endocrine systems.

Osteoprotegerin Levels Decrease in Abstinent Alcohol-Dependent Patients.

BACKGROUND: Osteoprotegerin (OPG) is a parameter of increasing interest in the search for pathophysiological mechanisms of reduced bone mineral density (BMD). It has been shown to be increased in alcohol-dependent subjects. In our study, we wanted to examine whether changes in OPG and receptor activator of the nuclear factor-κB ligand (RANKL) levels during an 8-week abstinence period in alcohol-dependent patients treated in an alcohol rehabilitation clinic would occur and whether alcohol-related variables, smoking, status, or physical activity prior to the study served as an influence on BMD and on OPG/RANKL levels. METHODS: Forty-three patients, who were abstinent not longer than a week, were included in the study. OPG and RANKL as well as other markers of bone metabolism were measured at baseline, and after 8 weeks of treatment, BMD was measured once. RESULTS: OPG levels decreased significantly, while osteocalcin, a marker of bone formation, increased significantly. RANKL as well as RANKL/OPG ratio, Serum CrossLaps, and all examined hormones showed no significant changes over time. Inflammatory parameters showed a significant reduction after 8 weeks. We detected no influence of potentially confounding variables of alcohol dependency on the course of OPG or other laboratory values. CONCLUSIONS: Our results could point to the well-known risk for reduced BMD in these patients being reversible with abstinence through an excess of bone formation. We also confirmed earlier findings that inflammatory processes play a role in the pathogenesis of alcohol-induced disturbances in bone metabolism.

Thyroid function parameters in normal pregnancies in an iodine sufficient population.

BACKGROUND: The aim of this retrospective observational study was to describe thyroid function parameters (fT3, fT4 and TSH) in the course of normal pregnancies. METHODS: Data were obtained between 2006 and 2007 at the University Hospital in Innsbruck, Austria. The starting point was the identification of women who had had a normal birth as recorded in the birth registry of Tyrol. Thyroid function parameters were determined using methods implemented at the Department of Nuclear Medicine in Innsbruck. RESULTS: The fT3 and fT4 values were normally distributed. Grouping the results by trimester revealed the following values: 4.93 ± 0.59, 4.54 ± 0.48, and 4.27 ± 0.45 pmol/l for fT3; and 15.23 ± 2.43, 13.79 ± 1.99, and 13.32 ± 0.2.01 pmol/l for fT4, respectively. The values corresponding to the 10th-percentile were 3.9 pmol/l for fT3 and 11.3 pmol/l for fT4, respectively. TSH values showed a typical left skewed distribution, thus the mean values were calculated after log transformation of the data. The corresponding mean trimestral values for TSH were 1.46 ± 1.29, 1.68 ± 1.23, and 1.70 ± 2.22 mIU/l, respectively. CONCLUSION: In an iodine sufficient population, thyroid function parameters in normal pregnancies do not differ from those in non-pregnant women. Our previously defined reference range for TSH of 0.3 to 3.5 mIU/l is equally valid for normal pregnancies. GENERAL SIGNIFICANCE: The question of cognition and IQ development of children has been proposed to be associated with thyroid function. The addition of data regarding normal thyroid function during pregnancy will contribute to this research.

The role of magnesium and thyroid function in early pregnancy after in-vitro fertilization (IVF): New aspects in endocrine physiology.

BACKGROUND: The initiation of a pregnancy is a process that requires adequate energetic support. Recent observations at our Institution suggest a central role of magnesium in this situation. The aim of this study was to evaluate magnesium, zinc, selenium and thyroid function as well as anti-Müllerian hormone in early pregnancy following in-vitro fertilization as compared to spontaneous successful pregnancies. RESULTS: A successful outcome of pregnancy after IVF treatment was associated with 2 parameters: higher levels of anti-Müllerian hormone as well as higher levels of magnesium in the pre-stimulation blood sample. These two parameters, however, showed no correlation. Spontaneous pregnancies as well as pregnancies after IVF show a fall of magnesium levels at 2-3 weeks of gestation. This drop of magnesium concentration is larger following IVF as compared to spontaneous pregnancies. Parallel to these changes TSH levels showed an increase in early IVF-pregnancy. At this time point we also observed a positive correlation between fT4 and TSH. This was not observed in spontaneous pregnancies. Thyroid antibodies showed no correlation to outcomes. CONCLUSIONS: In connection with the initiation of pregnancy following ovarian stimulation dynamic changes of magnesium and TSH levels can be observed. A positive correlation was found between fT4 and TSH in IVF pregnancies. In spontaneous pregnancies smaller increases of TSH levels are related to higher magnesium levels. GENERAL SIGNIFICANCE: We propose that magnesium plays a role in early pregnancy as well as in pregnancy success independently from anti-Müllerian hormone. Neither thyroid hormones nor thyroid antibodies were related to outcome.

The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation.

BACKGROUND: The aim of this study was to discern whether a relation between biochemical parameters, sonography and musculoskeletal data exists in cases of hyperthyroidism and whether they are modifiable through supplementation with selenomethionine and magnesium citrate as well as by acupuncture and manual medicine methods. RESULTS: A direct correlation between whole blood selenium and serum magnesium was found in subjects without thyroid disease and in menopausal women while it was reversed in cases of thyroid diseases as well as in patients with depression, infection, and in infertile women. Vascularization indices were elevated in cases of newly diagnosed benign thyroid diseases. Musculoskeletal changes i.e. lateral tension and idiopathic moving toes, as well as situations of physical and psychological stress and minor trauma and infection led to an increase of vascularization. Magnesium levels correlated negatively with these two conditions. The supplementation brought a reduction of the vascularization indices and reduced the incidence of idiopathic moving toes. Treatment of lateral tension required manual medicine methods and acupuncture (gastrocnemius). A small subgroup of patients showed a further reduction of hyper-vascularization after receiving coenzyme Q10. CONCLUSIONS: We interpret the elevated thyroid vascularization and low magnesium levels as signs of an inflammatory process related to the musculoskeletal changes. Improvement of thyroid function and morphology can be achieved after correcting the influence of stressors together with the supplementation regime. We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10.

Proof of concept of the WOMED model of benign thyroid disease: Restitution of thyroid morphology after correction of physical and psychological stressors and magnesium supplementation.

BACKGROUND: The aim of this study was to investigate the influence of a combined supplementation with magnesium, selenium and coenzyme Q10 on the morphology of the thyroid in patients with benign diseases. The clinical examination and treatment approach aims additionally at treating musculoskeletal and psychological stress. METHODS: A group of 8 patients (5 with hyperthyroidism, 3 with hypothyroidism) who initially attended a public institution received additional treatment at our private institution. The basic pharmacological treatment, i.e. substitution or thyreostatic, was kept unchanged. The inclusion of patients required good quality ultrasound images to be available. RESULTS: Initially the changes of the musculoskeletal system were corrected. Following this, stress components were also treated. After a period of 2-4 years of supplementation we observed a normalization of thyroid morphology as evidenced on ultrasound while at the same time there was a reduction of perfusion intensity. Thyroid antibody titers decreased in the majority of cases. Failure of the treatment was seen in 2 cases of chronic thyroiditis that was present for more than 10 years. The ultrasound images of these patients suggest a possible fibrosis. CONCLUSIONS: In spite of the limitation due to the small number of cases, our observational study has delivered proof of concept for our examination and treatment model for benign thyroid disease. GENERAL SIGNIFICANCE: Our results challenge validity of the prevailing dogma of a destructive unstoppable "autoimmune" destructive process of the gland. At the same time it shows new therapeutic options for patients with thyroid disease.

Multifactorial determinants of cognition - Thyroid function is not the only one.

BACKGROUND: Since the 1960s hypothyroidism together with iodine deficiency have been considered to be a principal determinant of cognition development. Following iodine supplementation programs and improved treatment options for hypothyroidism this relation might not be valid in 2015. On the other hand neurosciences have added different inputs also related to cognition. SCOPE OF REVIEW: We will examine the characteristics of the original and current publications on thyroid function and cognition and also add some general determinants of intelligence and cognition. One central issue for us is the relation of stress to cognition knowing that both physical and psychological stress, are frequent elements in subjects with thyroid dysfunction. We have considered a special type of stress called pre-natal stress which can influence cognitive functions. Fear and anxiety can be intermingled requiring mechanisms of fear extinction. MAJOR CONCLUSIONS: Recent studies have failed to show an influence of thyroid medication during pregnancy on intellectual development. Neuroscience offers a better explanation of cognition than hypothyroidism and iodine deficiency. Additional factors relevant to cognition are nutrition, infection, prenatal stress, and early life stress. In turn stress is related to low magnesium levels. Magnesium supplementation can correct both latent hypothyroidism and acquired mild cognitive deficits. GENERAL SIGNIFICANCE: Cognition is a complex process that depends on many determinants and not only on thyroid function. Magnesium deficiency appears to be a basic mechanism for changes in thyroid function as well as of cognition.

Markers of bone resorption and formation during abstinence in male alcoholic patients.

BACKGROUND: Reduced bone mineral density (BMD) is commonly found in alcohol-dependent patients. Many risk factors have been reported, yet the course of markers of bone formation and resorption in abstinent alcoholic patients have not received much attention. METHODS: In a prospective longitudinal study, we investigated BMD in male abstinent inpatients of an alcohol rehabilitation clinic aged 21 to 50 years at baseline and after 8 weeks of treatment. At baseline and at week 8, all patients had blood drawn for the analysis of liver function tests, calcium, phosphate, parathormone, 25-hydroxyvitamin D, osteocalcin (OC), serum crosslaps, sex hormones, and prolactin. BMD was determined by dual X-ray absorptiometry in the lumbar spine and the proximal right femur. We also determined the amount of physical activity prior to inpatient treatment by using the International Physical Activity Questionnaire (IPAQ). RESULTS: Low BMD was found in 15.1% of the patients for the lumbar spine, in 5.7% for the femoral neck, and in 1.9% for the total hip. BMD differed significantly from normal values, in the lumbar spine and in the femoral neck. At baseline, crosslaps were elevated in 34% of the patients, while OC levels were lowered in 17%. Over the course of the 8 weeks, we found a significant increase in OC plasma levels, indicating a higher rate of bone formation during continuous abstinence. There were also positive correlations between IPAQ scores and BMD as reflected by Z-scores in all regions, pointing to a protective effect of physical activity. CONCLUSIONS: In summary, this report confirms earlier cross-sectional studies of lowered BMD in alcoholic noncirrhotic men. We could also demonstrate that the initial imbalance between bone formation and resorption seems to adjust toward a balance between the two during abstinence.

Somatostatin receptor SPECT.

Somatostatin is a peptide with a broad distribution in the nervous system and acts as a neurotransmitter in several organs, having a wide range of mainly inhibiting effects, such as the suppression of growth hormone release, as well as the inhibition of pancreatic and gastrointestinal hormone release. Five somatostatin receptor subtypes have been cloned and demonstrated to have an emphasized expression in all human tumours. In particular, type 2 receptors were identified as the most frequently represented on the surface of neuroendocrine tumour cells, providing the molecular basis for many clinical applications of somatostatin analogues. Towards the end of the 1980s, the in vivo demonstration of somatostatin receptors on the surface of some tumours raised interest in receptor imaging, and indeed the peptide receptor overexpression on tumour cells, as compared to normal tissues, constitutes the basis for molecular imaging of these tumours. This review intends to illustrate the development of single photon emission radiopharmaceuticals for the study of somatostatin receptors and their application in diagnostic imaging.

[99mTc]demotensin VI: biodistribution and initial clinical results in tumor patients of a pilot/phase I study.

PURPOSE: Neurotensin subtype 1 receptor overexpression is found in a variety of human tumors. The aim of this pilot/phase I study was to assess the safety profile, pharmacokinetics, and imaging characteristics of (99m)Tc-Demotensin VI in tumor patients. METHODS: Scintigraphy with (99m)Tc-Demotensin VI was performed in 14 patients (2 female and 12 male) with advanced tumor stages. The diagnoses were pancreatic adenocarcinoma (n=4), small cell lung cancer (SCLC) (n=4), non-small cell lung cancer (NSCLC) (n=4), and colon carcinoma (n=2). Patients were injected with 500-550 MBq (99m)Tc-Demotensin VI. Blood samples were taken at various time points and urine was also collected up to 24 hours post-injection (p.i.) Planar images were acquired at 15-30 minutes, 1-2 hours, 4 hours, and 24 hours p.i. with additional SPECT imaging at 4 hours. RESULTS: Radiochemical purity always exceeded 95% up to 4 hours. Urinary and blood excretion was rapid with 5.05% ID (mean: n=5) in plasma after 4 hours. No side effects were observed after injection of (99m)Tc-Demotensin VI. Focal tracer accumulation was observed in 3 patients with brain metastases due to NSCLC, although specificity of this uptake could not be proven. Further, no tumor-related findings were observed. Although stability tests in human plasma revealed that (99m)Tc-Demotensin VI remained intact up to 2 hours incubation, ex vivo urine analysis indicated rapid metabolism. CONCLUSION: (99m)Tc-Demotensin VI was well tolerated by patients and showed favorable pharmacokinetics; however, tumor targeting was limited to brain metastases. Further studies on stability issues and receptor characterization in tumors are warranted to introduce neurotensin receptors (NTSR) imaging into the clinic.

Reflections on the theory of "silver bullet" octreotide tracers: implications for ligand-receptor interactions in the age of peptides, heterodimers, receptor mosaics, truncated receptors, and multifractal analysis.

The classical attitude of Nuclear Medicine practitioners on matters of peptide-receptor interactions has maintained an intrinsic monogamic character since many years. New advances in the field of biochemistry and even in clinical Nuclear Medicine have challenged this type of thinking, which prompted me to work on this review. The central issue of this paper will be the use of somatostatin analogs, i.e., octreotide, in clinical imaging procedures as well as in relation to neuroendocirne tumors. Newly described characteristics of G-protein coupled receptors such as the formation of receptor mosaics will be discussed. A small section will enumerate the regulatory processes found in the cell membrane. Possible new interpretations, other than tumor detection, based on imaging procedures with somatostatin analogs will be presented. The readers will be taken to situations such as inflammation, nociception, mechanosensing, chemosensing, fibrosis, taste, and vascularity where somatostatin is involved. Thyroid-associated orbitopathy will be used as a model for the development of multi-agent therapeutics. The final graphical summary depicts the multifactorial properties of ligand binding.

131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging.

The aim of this document is to provide general information about mIBG scintigraphy in cancer patients. The guidelines describe the mIBG scintigraphy protocol currently used in clinical routine, but do not include all existing procedures for neuroendocrine tumours. The guidelines should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guidelines have been prepared for nuclear medicine physicians and intend to offer assistance in optimizing the diagnostic information that can currently be obtained from mIBG scintigraphy. The corresponding guidelines of the Society of Nuclear Medicine (SNM) and the Dosimetry, Therapy and Paediatric Committee of the EANM have been taken into consideration, and partially integrated into this text. The same has been done with the most relevant literature on this topic, and the final result has been discussed within a group of distinguished experts.

Evaluation of Applied Kinesiology meridian techniques by means of surface electromyography (sEMG): demonstration of the regulatory influence of antique acupuncture points.

BACKGROUND: The use of Applied Kinesiology techniques based on manual muscle tests relies on the relationship between muscles and acupuncture meridians. Applied Kinesiology detects body dysfunctions based on changes in muscle tone. Muscle tonification or inhibition within the test setting can be achieved with selected acupoints. These acupoints belong to either the same meridian or related meridians. The aim of this study is to analyze muscle sedation and tonification by means of surface electromyography. METHODS: Manual muscle tests were carried out using standard Applied Kinesiology (AK) techniques. The investigation included basic AK procedures such as sedation and tonification with specific acupoints. The sedation and tonification acupoints were selected from related meridians according to the Five Elements. The tonification effect of these acupoints was also tested while interfering effects were induced by manual stimulation of scars. The effects of selective neural therapy, i.e. individually tested and selected anesthetic agent, for the treatment of scars were also studied. The characteristics of muscle action were documented by surface electromyographys (sEMG). RESULTS: The sEMG data showed a diminution of signal intensity when sedation was used. Graded sedation resulted in a graded diminution of signal amplitude. Graded increase in signal amplitude was observed when antique acupuncture points were used for tonification. The tactile stretch stimulus of scars localized in meridian-independent places produced diminution of signal intensity on a reference muscle, similar to sedation. These changes, however, were not corrected by tonification acupoints. Correction of these interferences was achieved by lesion specific neural therapy with local anesthetics. CONCLUSION: We demonstrated the central working principles, i.e. sedation and tonification, of Applied Kinesiology through the use of specific acupoints that have an influence on manual muscle tests. Sedation decreases RMS signal in sEMG, whereas tonification increases it. Interfering stimuli from scars were corrected by selective neural therapy.

Low bone mineral density and impaired bone metabolism in young alcoholic patients without liver cirrhosis: a cross-sectional study.

BACKGROUND: Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol's direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. METHODS: In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1-L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. RESULTS: In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z-score < or = -2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D < 30 ng/ml). CONCLUSIONS: Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism.

Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study.

BACKGROUND: Age- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSHbasal (TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences. METHODS: 2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 - 12 months, and 1 - 5, 6 - 10, 11 - 14, and 15 - 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia(R) Centaur automated immunoassay system. RESULTS: The final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age. CONCLUSION: Our results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.