Search

Autoimmune thyroid disease (ATD) is the most frequent cause of acquired thyroid dysfunction, most commonly presenting either as Hashimoto's thyroiditis or Graves' Disease. Hashimoto's thyroiditis is characterized by the presence of thyroid-specific autoantibodies, more commonly anti-thyroperoxidase antibodies in the serum and the typical inhomogeneous echostructure of the thyroid on a thyroid ultrasound examination. Hashimoto's thyroiditis can for a long time be accompanied by normal thyroid function and hypothyroidism can only progressively be established. Graves' disease is much less frequent in childhood and adolescence and presents with overt hyperthyroidism. After the onset of puberty, ATD affects females with a higher incidence than males, while during the prepubertal period there is not such a clear preponderance of affected females. ATD can occur either isolated or in the context of other autoimmune disorders, such as type 1 Diabetes mellitus (T1D), celiac disease, alopecia areata, vitiligo, etc. Especially at the pediatric age, a higher incidence of ATD is also observed in the context of specific genetic syndromes, such as trisomy 21 (Down syndrome), Klinefelter syndrome, Turner syndrome, or 22q11.2 deletion syndrome. Nevertheless, although thyroid dysfunction may also be observed in other genetic syndromes, such as Prader-Willi or Williams syndrome, the thyroid dysfunction in these syndromes is not the result of thyroid autoimmunity. Interestingly, there is emerging evidence supporting a possible link between autoimmunity and RASopathies. In this review article the incidence, as well as the clinical manifestation and accompanied pathologies of ATD in specific genetic syndromes will be presented and regular follow-up for the early identification of the disorder will be proposed. © Copyright © 2020 Kyritsi and Kanaka-Gantenbein.

Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6–8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. Conclusion: Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine.What is Known:• Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism.What is New:• Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

A 33-year-old Caucasian woman was referred at 24 + 3 weeks of gestation due to fetal tachycardia and hydrops. She had an uncomplicated pregnancy 16 years previously and was on levothyroxine after total thyroidectomy for Graves’ disease 6 years previously, when she developed moderate exophthalmos. Laboratory evaluation revealed appropriate thyroid function for this time of gestation: thyroid stimulating hormone (TSH) 1.7 μU/ml (1–3), fT4 18.53 pmol/l (12−22), with positive antibodies: anti-TPO 157 U/ml (

Puberty is a major developmental stage. Damaging mutations, considered as “mistakes of nature”, have contributed to the unraveling of the networks implicated in the normal initiation of puberty. Genes involved in the abnormal hypothalamic–pituitary–gonadal (HPG) axis development, in the normosmic idiopathic hypogonadotropic hypogonadism (nIHH), in the X-linked or autosomal forms of Kallmann syndrome and in precocious puberty have been identified (GNRH1, GNRHR, KISS1, GPR54, FGFR1, FGF8, PROK2, PROKR2, TAC3, TACR3, KAL1, PROK2, PROKR2, CHD7, LEP, LEPR, PC1, DAX1, SF-1, HESX-1, LHX3, PROP-1). Most of them were found to play critical roles in HPG axis development and regulation, the embryonic GnRH neuronal migration and secretion, the regulation and action of the hypothalamic GnRH. However, the specific neural and molecular mechanisms triggering GnRH secretion remain one of the scientific enigmas. Although GnRH neurons are probably capable of autonomously generating oscillations, many gonadal steroid-dependent and -independent mechanisms have also been proposed. It is now well proven that the secretion of GnRH is regulated by kisspeptin as well as by permissive or opposing signals mediated by neurokinin B and dynorphin. These three supra-GnRH regulators compose the kisspeptin-neurokinin B-dynorphin neuronal (KNDy) system, a key player in pubertal onset and progression. Moreover, an ongoing increasing number of inhibitory, stimulatory and permissive networks acting upstream on GnRH neurons, such as GABA, NPY, LIN28B, MKRN3 and others integrate diverse hormonal and peripheral signals and have been proposed as the “gate-keepers” of puberty, while epigenetic modifications play also an important role in puberty initiation. © 2017, Italian Society of Endocrinology (SIE).

The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the NOTCH-1 gene. On the background of 22q13 deletion syndrome and data from animals on the effect of abnormal NOTCH-1 gene expression on kisspeptin neuron formation, we discuss the probable role of Notch signaling in the premature activation of the HPG axis. © 2016 Walter de Gruyter GmbH, Berlin/Boston.

An earlier adiposity rebound, suggestive of adult obesity, has been reported in children with congenital hypothyroidism. We undertook this study to evaluate the effect of congenital hypothyroidism on: 1) the timing of adiposity rebound, 2) the long-term prognosis of BMI status, and 3) the factors potentially affecting adiposity in subjects with congenital hypothyroidism. We found that in children with congenital hypothyroidism the BMI values were higher during the first years of life compared to normal population, but subsequently normalized. After the initial rise of BMI, the decline (nadir) and subsequent rise (adiposity rebound), usually occurring in normal children at an age greater than 30 months, was less evident in our group of children with congenital hypothyroidism. The severity of hypothyroidism affected BMI values at 6 and 12, but not at 36 months of age. In conclusion, in children with congenital hypothyroidism, 1) the high BMI values in early childhood normalize in adolescence, and 2) the normally expected BMI fluctuations during the first years of life are attenuated. These findings constitute indirect evidence that thyroid function during fetal and neonatal life affects BMI status during the first years of life.

The central nervous system is often affected in patients with congenital toxoplasmosis. However, hypothalamo-pituitary dysfunction has rarely been reported in children with congenital toxoplasmosis, and no case with prolonged fever of central origin has been documented so far. We describe a newborn with congenital toxoplasmosis who presented with fever due to hypothalamo-pituitary dysregulation and combined hypothalamo-pituitary deficiencies consisting of central diabetes insipidus, hypothyroidism and ACTH deficiency. © Freund Publishing House Ltd., London.

Background: Art increased prevalence of autoimmune (Hashimoto’s) thyroiditis in adult patients with vitiligo has been described. This association has scarcely been studied in children. Objective. We sought to assess children and adolescents with vitiligo for autoimmune thyroid disorder and to identify any predisposing factors of this association. Methods: In all, 54 children and adolescents (23 boys, 31 girls; mean age 11.4 years) with known vitiligo were studied by physical examination and laboratory studies. Results: Four patients with vitiligo were already known to have Hashimoto’s thyroiditis. in 9 of the remaining 50 patients, autoimmune thyroiditis was revealed at the time of the investigation. Of the 54 patients with vitiligo, 13 (24.1%) had autoimmune thyroiditis as compared with 9.6% of school-aged children from an iodine-replete area of Greece (P = .002). There was no association between thyroiditis and clinical type of vitiligo, age at onset, mean duration of vitiligo, or sex. Conclusions: Hashimoto’s thyroiditis is 2.5 times more frequent among children and adolescents with vitiligo than in a healthy age- and sex-matched Population. It usually follows the onset of vitiligo. We propose that children and adolescents with vitiligo should be screened annually for thyroid dysfunction, particularly autoimmune thyroiditis.

Objective: To identify the genetic defect in a neonate presented with prolonged jaundice and central hypothyroidism. Design: Central hypothyroidism was detected in a neonate initially examined for prolonged jaundice, and levothyroxine therapy was initiated. Direct sequencing of the Prop1 gene was carried out and pituitary function and morphology were evaluated using hormonal testing and magnetic resonance imaging (MRI) respectively. Methods: Dynamic hormonal testing was carried out using established methodologies. Hormones were determined by RIA or chemiluminescence immunoassays. Genomic analysis of the Prop1 gene was performed by direct sequencing. MRI protocol: sagittal spin echo T2-weighted scans 2500/90 (TR/TE). plain and contrast-enhanced sagittal and coronal spin echo T1-weighted scans 500/20 (TR/TE). Results: Low thyroid hormones (coupled with lack of TSH rise), low GH, normal cortisol and normal prolactin values were detected. Direct sequencing revealed the presence of two mutations in the Prop1 gene: GA296del and Q83X. The 083X was further confirmed by PvuII restriction digestion and represented a novel Prop1 gene mutation. which was not detected in 100 controls tested. Pituitary enlargement was detected, with respect to normal-for-age controls. Conclusions: (i) The Q83X mutation extends the spectrum of Prop1 gene mutations: (ii) central hypothyroidism in a neonate might constitute the initial sign of Prop1 gene defect; (iii) the patient is the youngest individual with Prop1 gene defect and pituitary enlargement presented to date; and (iv) early detection of Prop1 gene mutations facilitates genetic counseling and ensures prompt management of the anticipated hormonal insufficiencies.

Retinol Binding Protein-4 (RBP-4), the action of which was initially thought to be only the transport of vitamin A, is a major circulating adipocytokine involved in the inflammation. We evaluated the serum RBP-4 levels in children with inflammatory bowel disease (IBD) and correlated them with transthyretin (TTR), inflammation markers, disease activity, and body mass index (BMI).In 41 children of mean age 11.9 ± 3.6 years (range 5-17.7 y) with IBD (19 with Crohn's disease (CD) and 22 with Ulcerative colitis (UC) serum RBP-4, TTR, Amyloid A (SAA), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), disease activity and BMI were prospectively determined and compared with those of 42 matched controls.No difference in the RBP-4 and TTR serum levels, between patients and controls as well as between active and remission state of the disease was noticed. A negative correlation of serum RBP-4 with the disease activity, SAA and ESR and a positive correlation with TTR was found, but no significant correlation with CRP or BMI was found. Inflammation markers were significantly increased in patients compared to controls and had a positive correlation with the disease activity.RBP-4 negatively correlated with disease activity of children with IBD probably indicating a protective anti-inflammatory mechanism of action in addition to transport of vitamin A.