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Background: After thyroidectomy, patients require Levothyroxine (LT4). It may take years of dose adjustments to achieve euthyroidism. During this time, patients encounter undesirable symptoms associated with hypo- or hyper-thyroidism. Currently, providers adjust LT4 dose by clinical estimation, and no algorithm exists. The objective of this study was to build a decision tree that could estimate LT4 dose adjustments and reduce the time to euthyroidism., Methods: We performed a retrospective cohort analysis on 320 patients who underwent total or completion thyroidectomy at our institution. All patients required one or more LT4 dose adjustments from their initial postoperative dose before attaining euthyroidism. Using the Classification and Regression Tree algorithm, we built various decision trees from patient characteristics, estimating the dose adjustment to reach euthyroidism., Results: The most accurate decision tree used thyroid-stimulating hormone values at first dose adjustment (mean absolute error = 13.0 μg). In comparison, the expert provider and naïve system had a mean absolute error of 11.7 μg and 17.2 μg, respectively. In the evaluation dataset, the decision tree correctly predicted the dose adjustment within the smallest LT4 dose increment (12.5 μg) 79 of 106 times (75%, confidence interval = 65%-82%). In comparison, expert provider estimation correctly predicted the dose adjustment 76 of 106 times (72%, confidence interval = 62%-80%)., Conclusions: A decision tree predicts the correct LT4 dose adjustment with an accuracy exceeding that of a completely naïve system and comparable to that of an expert provider. It can assist providers inexperienced with LT4 dose adjustment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Maternal iodine deficiency is related to high neonatal thyroid-stimulating hormone (TSH) values, with the threshold of 5 mIU/L recommended as an indicator of iodine nutrition status. The objective of this study was to analyse possible risk factors for increased TSH that could distort its validity as a marker of iodine status. The clinical relevance of this research question is that if the factors associated with iodine deficiency are known, iodine supplementation can be introduced in risk groups, both during pregnancy and in newborns., Methods: A case-control study was carried out in a sample of 46,622 newborns in 2002-2015 in Spain. Of these, 45,326 had a neonatal TSH value ≥5 mIU/L. The main variable was having TSH ≥5 mIU/L and the secondary variables were: sex, gestational age, day of sample extraction and maternal origin. Associated factors were analysed through a logistic regression model, calculating the odds ratio (OR)., Results: The factors associated with this outcome were: male sex (OR = 1.34, 95% CI: 1.20-1.50, p<0.001), originating from an Asian/Oceanic country (OR = 0.80, 95% CI: 0.54-1.20, p = 0.536) or Europe (OR = 0.80, 95% CI: 0.66-0.96, p = 0.285) (including Spain, OR = 1) [p<0.001 for America (OR = 0.54, 95% CI: 0.44-0.68) and p = 0.025 for Africa (OR = 0.78, 95% CI: 0.62-0.97)] and fewer days from birth to sampling (OR = 0.80, 95% CI: 0.77-0.82, p<0.001)., Conclusions: The risk of high neonatal TSH without congenital hypothyroidism is higher in males, decreases with a greater number of days from birth to extraction, and is dependent on maternal ethnicity but not on gestational age., Competing Interests: The authors have declared that no competing interests exist.

Background Severe obesity is associated with a number of cardiometabolic risk factors. Thyroid-stimulating hormone (TSH) levels are often slightly increased in children with obesity. The clinical significance of the mild elevation in TSH in children with obesity is unclear. Objective To examine the association between TSH and lipids in children with severe obesity. Methods We performed a retrospective analysis of records of children with severe obesity with simultaneous measurements of TSH and lipids. Children with TSH <0.3 mIU/L and ≥10 mIU/L were excluded. The relationship between TSH and lipids was evaluated using univariate/multiple variable linear and logistic regression. Results The study included 834 children (age 13.8 ± 4.1 years, males 46%, body mass index [BMI]: 36.9 ± 7.6 kg/m2; BMI z-score 2.6 ± 0.4). Seventy-four (8.9%) children had TSH between 5 and <10 mIU/L (high TSH [HTSH]). TSH was positively associated with non-high-density lipoprotein (HDL) cholesterol (β: 1.74; 95% confidence interval [CI] 0.29-3.20, p = 0.02). Total cholesterol and non-HDL cholesterol were higher in males with HTSH compared to those with normal TSH (175.5 vs. 163.5 mg/dL, p = 0.02 and 133.7 vs. 121.4 mg/dL, p = 0.02, respectively). The odds of elevated non-HDL cholesterol (≥145 mg/dL) was higher in males with HTSH relative to those with normal TSH (odds ratio [OR]: 2.78; 95% CI 1.35-5.69, p = 0.005). Conclusions TSH levels were positively associated with non-HDL cholesterol in children with severe obesity. Males with mildly elevated TSH had higher total cholesterol and non-HDL cholesterol compared to males with normal TSH. Further studies are warranted to determine if levothyroxine therapy would result in improvement in total cholesterol or non-HDL cholesterol in children with severe obesity with mildly elevated TSH.

Purpose: Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity., Methods: This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2-18.5) years, height SDS 0.27 ± 1.04 (-3.49-4.35), and BMI SDS 2.94 ± 0.59 (1.60-4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L., Results: Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p < 0.05), systolic (125.8 ± 13.5 vs 124.5 ± 13.1 mm/Hg), and diastolic blood pressure (79.2 ± 8.0 vs 77.9 ± 8.2 mm/Hg) than subjects of group A. No difference was observed in body composition, ODI, and the cardiovascular risk factors between these two groups., Conclusion: TSH elevation in overweight and obese children and adolescents, being associated with a higher TC and blood pressure, might negatively influence the cardiac status. Longitudinal studies are requested, however, to confirm this hypothesis and, therefore, to conclude whether a substitutive treatment with l-thyroxine is really needed in these patients.

Mercury (Hg) poisoning is considered a rare disease by the National Institutes of Health and the diagnosis can present great challenges to clinicians. Children who are exposed to Hg can present with a wide variety of symptoms, including acrodynia, tremor, excessive salivation, and psychiatric symptoms, including insomnia. However, endocrinologic manifestations from Hg exposure are less well known. This is a case report of a 12-year-old boy who presented with body rash, irritability, insomnia, and profuse sweating after returning from a summer camp. The child was initially managed in the outpatient setting, and the investigation was mainly targeted toward infectious etiology, including Rocky Mountain spotted fever and Lyme disease. He was eventually admitted to the hospital with altered mental status and was noted to have hyponatremia with serum sodium of 121 mEq/L. Thyroid studies also revealed elevated free thyroxine levels in the presence of normal triiodothyronine and thyrotropin. The patient developed hypertension and tachycardia, and was found to have elevated 24-hour vanillylmandelic acid and metanephrines. Finally, heavy metal measurements revealed a blood Hg level that was greater than the reference values of 0 to 9 ng/mL. Chelation treatment with 2,3-dimercaptopropane-1-sulfonate was subsequently initiated and over a period of 8 months his symptoms resolved and his thyroid function test returned to normal. This case highlights some of the challenges commonly encountered in identifying Hg exposure. More importantly, it illustrates that exposure to Hg should be considered in children who present with the symptoms and abnormal endocrinologic test results described in this report., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Iodine (I) deficiency has been known for more than a century and is known to cause cretinism at the extreme end of the spectrum but also, importantly, impaired development and neurocognition in areas of mild deficiency. The WHO has indicated that median urinary iodine of 100-199 μg/l in a population is regarded as indicative of an adequate iodine intake. The understanding of the spectrum of iodine deficiency disorders led to the formation of The International Council for the Control of Iodine Deficiency Disorders which has promulgated the use of household iodized salt and the use of such salt in food processing and manufacture. Iodine deficiency is particularly important in pregnancy as the fetus relies on maternal thyroxine (T4) exclusively during the first 14 weeks and also throughout gestation. As this hormone is critical to brain and nervous system maturation, low maternal T4 results in low child intelligence quotient. The recommendation for I intake in pregnancy is 250 μg/day to prevent fetal and child brain function impairment. During the past 25 years, the number of countries with I deficiency has reduced to 32; these still include many European developed countries. Sustainability of adequate iodine status must be achieved by continuous monitoring and where this has not been performed I deficiency has often recurred. More randomized controlled trials of iodine supplementation in pregnancy are required in mild iodine-deficient areas to inform public health strategy and subsequent government action on suitable provision of iodine to the population at risk.

Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by a hemizygous deletion of around 28 genes on the long arm of chromosome 7 (7q11.23), characterized by a unique spectrum of behavioral impairments, including mental retardation, deficits in visuospatial constructive cognition, hypersociability, anxiety and simple phobias. Physical characteristics include dysmorphic faces, short stature, oculomotor deficits, gross and fine coordination impairments, diminished control of balance and mild extrapyramidal signs as well as gait abnormalities resembling gait hypokinesia. Genes near the distal deletion breakpoint appear to contribute most to the WBS cognitive and behavioral profile and include the GTF family of transcription factors: GTF2I, GTF2IRD1, GTF2IRD2. We have previously shown that heterozygous deletions of GTF2IRD1 in humans and homozygous deletion in mice contributes to craniofacial abnormalities. Here we show an important role of this gene in motor coordination and anxiety ascertained from extensive behavioral mouse phenotyping. Gtf2ird1 null mice showed lower body weight, decreased spontaneous and circadian locomotor activity, diminished motor coordination and strength, gait abnormalities, increased anxiety and an elevated endocrinological response to stress. Gtf2ird1 heterozygous mice displayed lower body weight and decreased circadian activity, but only minor motor coordination and anxiety-related behavioral dysfunctions. Our study strongly supports a role for GTF2IRD1 in the motoric and anxiety-related abnormalities seen in Williams-Beuren syndrome, and suggests basal ganglia and potentially cerebellar abnormalities in Gtf2ird1 mice., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose of Review: In recent years, there has been an increasing focus on thyroid function in obese children. There is controversy concerning whether the changes in the levels of thyroid hormones and thyroid-stimulating hormone (thyrotropin - TSH) in obesity are causes or consequences of weight status and whether these subtle differences merit treatment with thyroxine. This review aimed to study the prevalence of disturbed thyroid hormone and TSH values in childhood obesity and the underlying pathophysiologic mechanisms linking obesity to thyroid function., Recent Findings: In the past 18 months, four studies demonstrated moderate elevation of TSH concentrations in 10-23% of obese children, which was associated with normal or slightly elevated thyroxine and triiodothyronine values. Two studies reported ultrasonographic hypoechogenicity of the thyroid in obese children with hyperthyrotropinemia, which was not caused by autoimmune thyroiditis; therefore, the authors hypothesized a link to chronic inflammation in obesity. Weight loss led to a normalization of elevated TSH levels in two studies. The adipokine leptin is the most promising link between obesity and hyperthyrotropinemia since leptin stimulates the hypothalamic-pituitary-thyroid., Summary: The elevated TSH levels in obesity seem a consequence rather than a cause of obesity. Therefore, treatment of hyperthyrotropinemia with thyroxine seems unnecessary in obese children.

Thyrotropin receptor blocking antibodies are a rare cause of hyperthyrotropinaemia and more rarely of congenital hypothyroidism. We report a case of hyperthyrotropinaemia but normal thyroid hormone in the newborn of a mother with hypothyroidism treated with thyroxine. Two older siblings had similar high thyrotropin and normal thyroid function in the newborn period which did not require hormone treatment and resolved spontaneously. Demonstration of thyrotropin receptor antibodies in the child confirmed our diagnosis. Our case was not treated with thyroid replacement hormone and has remained biochemically euthyroid, with thyrotropin levels returning to normal over a period of months.

Assisted reproductive technologies (ARTs) have been widely used during the last three decades and progressively more children are born with the help of such methods. There is now evidence that ARTs may be associated with slight epigenetic modifications in the expression of several genes that could have a long-term impact on the health of the offspring. Also, a clear association between such techniques and genomic imprinting abnormalities has been reported. The neuroendocrine impact of ART on the offspring includes slight elevations of systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as increased circulating triglyceride concentrations, in children born after ART, especially in those with rapid catch-up growth in weight during early childhood. However, the postnatal growth of most children after ART is normal and no increased incidence of the full metabolic syndrome has been observed in these children and adolescents. Moreover, the pace and timing of puberty of such children is normal and no increased incidence of premature adrenarche could be discerned in ART children in the absence of restricted fetal growth. Finally, a slight modification of the set point of thyroid stimulating hormone sensitivity was observed in ART children, without an apparent impact on thyroid hormone secretion. This has been attributed to epigenetic changes. Questions remain to be answered regarding the future reproductive capacity of children born after ART, as well as their cardiovascular risk in later adult life. Long-term prospective studies should be performed to provide robust evidence., (Copyright 2010 Elsevier B.V. All rights reserved.)

Unlabelled: Thyroid function tests were carried out on 320 children with Down's syndrome aged between 5 d and 10 y. Thyroid function was normal in 230 patients (71.9%) and abnormal in 90 (28.1%). Six patients (1.8%) had primary congenital hypothyroidism, one patient had acquired hypothyroidism and two had transient hyperthyrotropinaemia of the newborn. Sixteen of the remaining 81 patients (25.3%) had compensated hypothyroidism with increased thyroid-stimulating hormone (TSH) levels (11-20 mU l(-1)). Their T4 levels were found to be either normal or close to the lower limit of normal. These cases were started on thyroxine therapy. Sixty-five of the 81 patients had a mild compensated hypothyroidism with mild TSH elevation (6-10 mU l(-1)). None of the patients had hyperthyroidism. The antithyroid antibodies were positive in the acquired hypothyroidism case., Conclusion: The prevalence of congenital hypothyroidism was 1.8% in children with Down's syndrome while 25.3% of them had compensated hypothyroidism. It is suggested that Down's syndrome patients with normal thyroid functions and those with compensated hypothyroidism should be followed annually and every 3 mo, respectively. Besides congenital hypothyroidism cases, those with TSH levels between 11 and 20 mU l(-1) may benefit from treatment with low-dose thyroxine.

We had previously shown that BALB/c mice immunized with the extracellular domain of human thyrotropin receptor (ETSHR) developed moderate hyperthyroxinemia. The antibody responses in these mice were predominantly of the IgG1 subclass. Since cholera toxin B subunit (CT-B) has direct effects on the thyroid, and is known to activate B lymphocytes and cause enhanced IgG1 production, we tested the ability of CT-B to modulate the antibody response to ETSHR. CT-B is unique in that it not only elicits a strong immune response to itself, but more importantly, when given with other antigens acts as a potent adjuvant. In the present study, BALB/c mice given ETSHR with CFA or CT-B via ip route showed higher titers of antibodies to ETSHR when compared to mice similarly immunized with ETSHR alone, or with IFA. Antibodies in ETSHR+CT-B immunized mice were mostly of the IgG1 subclass and reacted predominantly with ETSHR peptides 1 (aa 22-41), 21 (aa 322-341), and 23 (352-371). In contrast, animals immunized with ETSHR+CFA showed IgG1, IgG2a and IgG2b responses and reacted with peptides 1 and 21. Furthermore, mice immunized with ETSHR along with CT-B showed significantly higher levels of thyrotropin (TSH) binding inhibitory immunoglobulins (TBII) compared to those that did not receive CT-B. None of the mice immunized with a control antigen showed antibody response to ETSHR. These results suggested that CT-B could enhance and modulate immune response to ETSHR., (Copyright 2000 Academic Press.)

History: An increased concentration of free T3 (fT3) with normal TSH was repeatedly measured in a 58-year-old man with diarrhoea. Hyperthyroidism was diagnosed and he was treated with thyrostatic drugs., Investigations: Referred to our clinic, fT4 concentration, determined by routine ELISA, was found to be raised to 33.9 pmol/l, while fT3 and TSH levels were within normal limits. But the equilibrium-dialysis method gave a normal serum level also for fT4. Gastroscopy suggested coeliac disease, confirmed histologically., Treatment and Course: The symptoms quickly improved on a gluten-free diet and the fT4 level returned to normal values even on routine measurement., Conclusion: The raised fT4 level with non-suppressed TSH was only revealed as a false finding by special non-routine laboratory methods. The reversibility and the close time relationship of the reported laboratory data with the clinical manifestations of the concomitant coeliac disease strongly suggested that changes in serum in the course of the latter disease played a role in these misleading laboratory results. An interference of coeliac disease with some laboratory tests has been previously described.

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. To our knowledge, no such documentation on Asians exists. Six of 8 members of a 3-generation Japanese family were found by us to carry the FDH phenotype. Serum total T4 levels ranged from 1763.2-2741.3 nmol/L (normal range, 65.6-164.7), serum total T3 levels ranged from 2.73-5.62 nmol/L (normal range, 1.47-2.95), and rT3 levels ranged from 1.08-2.52 nmol/L (normal range, 0.22-0.60). In the proband, the majority of [125I]T4 in serum T4-binding proteins was distributed in albumin fractions, and the isolated albumin had an increased affinity for T4. A guanine to cytosine transition in the second nucleotide of codon 218, resulting in replacement of normal arginine with proline, was detected in 1 of 2 alleles in all 5 subjects of the family with FDH. In all FDH-affected Caucasian subjects from 10 unrelated families with a moderate increase in serum T4, the guanine to adenine transition was demonstrated at the same position of the albumin gene as noted in our patients, but histidine, the replacement amino acid, differed from proline noted in our FDH Japanese subjects. It would thus appear that FDH has ethnic variations.

Introduction: Hyperthyroxinemia does not always equate to hyperthyroidism. Laboratory tests should always be correlated with the clinical picture. A mismatch should make one doubt true hyperthyroidism. The purpose of our study was to assess the etiology of euthyroid hyperthyroxinemia not associated with estrogen use or pregnancy and to review the outcome of those erroneously treated., Methods: The medical records of thirteen euthyroid patients with non estrogen associated hyperthyroxinemia were reviewed. They had a complete set of thyroid function tests including free T3 and free T4 by membrane dialysis, TRH stimulation test and thyroid hormone binding panel., Results: Two diagnostic groups were identified: Hyperthyroxinemia secondary to binding abnormalities (7/13), better known as familial dysalbuminemic hyperthyroxinemia (FDH) and hyperthyroxinemia secondary to Thyroid Hormone Resistance (THR) (6/13). The FDH group had an elevated T4 and FTI, with normal T3RU, TSH, TRH stimulation test but an abnormal thyroid hormone binding panel which was used to confirm the diagnosis. The THR group had two laboratory presentations: Four patients presented with all the thyroid hormone tests elevated (T4, T3, T3RU, FTI) including a free T3 and free T4 by membrane dialysis with a normal TSH and TRH stimulation test and a normal T4 binding panel. This presentation is typical for a TRH patient with a nuclear receptor defect where all the precursos to the defect accumulate. Two patients with THR presented elevated T4 and free T4 but normal T3 and free T3, localizing the defect at the level of the active T4 transport mechanism across the cellular membrane. These two patients had a normal TSH, TRH stimulation test and T4 binding panel. Two patients were treated erroneously with radioactive iodine and became extremely hypothyroid in spite of normal TFTs. Very high dose of thyroid hormone replacement were required to restore euthyroidism., Conclusion: One must suspect these two entities in patients clinically euthyroid who have elevated T4 but non-suppressed TSH. A normal TSH and TRH test confirm euthyroidism. A thyroid hormone binding panel differentiates FDH from THR. Neither group require treatment. If treated erroneously and T4 drops to normal values, one must again induce hyperthyroxinemia to restore euthyroidism in these patients.

In the United States and Western Europe, primary hepato-cellular carcinoma is an uncommon malignancy. Even though many well-defined associations have been reported, paraneoplastic manifestations are rare in North American patients. We describe an adolescent with complaints of weight loss, weakness, and a sensation of ¿fullness in the upper abdomen.¿ On initial laboratory workup a lactescent serum was found, with the following abnormalities; serum cholesterol level of 573 mg/dl (normal 120-260), triglycerides of 1,761 mg/dl (normal 10-190), and serum thyroxine level of 21 microgram/dl (normal 5.5-12.3). Serum albumin, calcium, and thyroid-stimulating hormone levels were also minimally elevated. Liver biopsy confirmed hepatocellular carcinoma. This is a rare hepatoma, which in our case manifested with multiple paraneoplastic phenomena, including hyperthyroxinemia, hypercholesterolemia, hypertriglyceridemia, and hyperalbuminemia. We review the pertinent literature.

Some of the point mutations in transthyretin (TTR) exhibit increased affinity for thyroxine (T4) and result in euthyroid hyperthyroxinemia in affected individuals. TTR, also known as thyroxine binding prealbumin, is a homotetrameric plasma protein of MW 55,000 that transports 15% of serum T4. The known point mutations that cause euthyroid hyperthyroxinemia are Ala109 (ACC) to Thr (GCC) and Gly6 (GGT) to Ser (AGT). These mutations are transmitted by autosomal dominant inheritance. The laboratory findings are an elevated total T4, an increased free T4 index, a normal free T4, and normal levels of total and free triiodothyronine. The Thr109 mutation abolishes Fnu4HI restriction site, and the Ser6 mutation eliminates the Msp I restriction site.

The term "hyperthyroxinemia" encompasses clinical syndromes associated with elevated levels of thyroid hormone in the presence of increased, normal, or decreased thyroid function. The clinical presentation (i.e., history and physical examination), in vitro thyroid function tests, as well as radioisotope thyroid imaging all play key roles in the diagnosis of the underlying thyroid disorder. Many of these disorders and their appearance on thyroid scintigraphy are presented in this atlas.

The aim of this study was determine (a) the causes of hyperthyroxinaemia and (b) the biochemical profile of thyrotoxicosis in a general hospital laboratory for one year using a sensitive TSH assay. Total T4 (TT4) and TSH were measured in all 8,382 samples and TT3, free T4, free T3 and thyroxine binding globulin (TBG) in selected cases. TT4 was elevated in 215 (2.6%). 159 (74%) were due to thyrotoxicosis; 41 (19%) to elevated TBG and 15 (7%) non-thyroidal illness. Thyrotoxicosis (serum TSH less than 0.15m U/1) occurred in 223 (2.7%) of all patients and was diagnosed with high TT4 in 159 (71%), normal due to intercurrent illness. 352 (4%) patients had suppressed TSH while all thyroid hormone values were normal. Thus TT4 may be elevated from causes other than thyrotoxicosis sufficiently frequently to necessitate routine TSH measurements. While Normal TSH measurements nearly always excludes thyrotoxicosis, suppressed values are insufficient to establish a diagnosis or monitor thyroxine replacement therapy.

This case report describes a 38-year-old male who was hospitalized for further clarification of clinically mild hyperthyroidism. His increased total hormone levels, the elevated free thyroid hormones and the elevated basal TSH with blunted response to TRH strongly suggested a pituitary adenoma with inappropriate TSH incretion. Transmission computed tomography showed an intrasellar expansion, 16 mm in diameter. The neoplastic TSH production was confirmed by an elevated alpha-subunit and a raised molar alpha-sub/TSH ratio. However, T4 distribution on prealbumin (PA, TTR), albumin (A) and thyroxine binding globulin (TBG) showed a clearly increased binding to PA (39%), indicating additional prealbumin-associated hyperthyroxinemia. The absolute values of PA, A and TBG were within the normal range. After removal of the TSH-producing adenoma, basal TSH, the free thyroid hormones and T4 binding to prealbumin returned to normal. Therefore, the prealbumin-associated hyperthyroxinemia had to be interpreted as a transitory phenomenon related to secondary hyperthyroidism (T4 shift from thyroxine binding globulin to prealbumin) rather than a genetically conditioned anomaly of protein binding.

The changes in calcemia and calciuria levels following low calcium diet have been studied in 35 patients with active urolithiasis and in 20 healthy subjects. Blood serum concentrations of thyroxine, cortisol and aldosterone in basal conditions as well as cortisol and aldosterone following stimulation with synacten were determined in addition. The levels of calcemia and calciuria (2.56 +/- 0.015 mmol/l and 4.70 +/- 0.41 mmol/10 mmoles of creatinine, respectively) were found to be significantly higher in patients with active urolithiasis than in healthy subjects. In addition, in patients with urolithiasis the basal blood serum concentrations of thyroxine and aldosterone were significantly higher than in healthy subjects, while the reactivity of cortisol and aldosterone secretion to synacten stimulation was normal. The results obtained suggest the participation of the described hormonal aberrations in the pathogenesis of active urolithiasis.

A case of euthyroid hyperthyroxinaemia caused by auto-antibodies to thyroxine and tri-iodothyronine is presented. Gel filtration chromatography of the patient's serum showed increased binding of radio-labelled thyroxine analogue to a macromolecular component, which migrated in the gammaglobulin region on electrophoresis. Precipitation by protein A confirmed that this was an immunoglobulin. The importance of recognising this condition so that inappropriate therapy can be avoided is stressed.

Serum thyroxine was significantly higher in 59 patients with hepatocellular carcinoma than in normal subjects, patients with uncomplicated cirrhosis (48), or other primary tumours with or without hepatic metastases (50). Elevated thyroxine levels appeared attributable to high levels of thyroxine binding globulin which showed a positive linear correlation with serum thyroxine in all groups studied. Despite this hyperthyroxinaemia all patients appeared clinically euthyroid and, consistent with this, T3 was elevated in only one patient and the free thyroxine index was normal in all. Amongst a group of 25 cirrhotic patients who were followed-up for between 12 and 72 months, there was a striking dissociation between the TBG values of those destined to develop HCC and those who did not. In the former group TBG rose steadily with time whereas in the latter group levels remained stable, or, more often, fell. The rises in TBG occurred prior to any clinical signs of tumour development and may be one of the earliest serological changes to occur during carcinogenesis in the cirrhotic liver.

The case of an 8-month-old infant with rickets and hyperthyroxinemia is described. Hyperthyroxinemia resolved following the treatment of the rickets. This association has not been reported previously.