Appetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity.

Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb.

Identification of genetic variants and phenotypic characterization of a large cohort of patients with congenital hypopituitarism and related disorders.

Purpose: Congenital hypopituitarism (CH) disorders are phenotypically variable. Variants in multiple genes are associated with these disorders, with variable penetrance and inheritance.

Methods: We screened a large cohort (N = 1765) of patients with or at risk of CH using Sanger sequencing, selected according to phenotype, and conducted next-generation sequencing (NGS) in 51 families within our cohort.

Approach to the Patient: Management of Pituitary Hormone Replacement Through Transition.

Hypopituitarism in childhood is a rare, complex disorder that can present with highly variable phenotypes, which may continue into adult life. Pituitary deficits can evolve over time, with unpredictable patterns resulting in significant morbidity and mortality. Hypopituitarism and hypothalamic dysfunction may be associated with challenging comorbidities such as obesity, learning difficulties, behavioral issues, sleep disturbance, and visual impairment.

A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas.

Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.

Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline.

Unexplained or idiopathic pituitary stalk thickening or central diabetes insipidus not only harbours rare occult malignancies in 40% of cases but can also reflect benign congenital defects. Between 2014 and 2019, a multidisciplinary, expert national guideline development group in the UK systematically developed a management flowchart and clinical practice guideline to inform specialist care and improve outcomes in children and young people (aged <19 years) with idiopathic pituitary stalk thickening, central diabetes insipidus, or both. All such cases of idiopathic pituitary stalk thickening and central diabetes insipidus require dynamic pituitary function testing, specialist pituitary imaging, measurement of serum β-human chorionic gonadotropin and alpha-fetoprotein concentrations, chest x-ray, abdominal ultrasonography, optometry, and skeletal survey for occult disease.

Sotos Syndrome Presenting with Neonatal Hyperinsulinaemic Hypoglycaemia, Extensive Thrombosis, and Multisystem Involvement.

Initially described as an uncommon presenting feature of Sotos syndrome (SoS), over the last decades, congenital hyperinsulinaemic hypoglycaemia (CHI) has been increasingly reported in association with this condition. The mechanism responsible for CHI in SoS is unclear. We report the case of a neonate presenting with CHI and extensive venous and arterial thrombosis associated with kidney, heart, liver, skeleton, and brain abnormalities and finally diagnosed with SoS on whole genome sequencing.

45,X/46,XY Mosaicism Presenting With Isolated Unilateral Cryptorchidism and a Normal Blood Karyotype.

Context: 45,X/46,XY mosaicism is a disorder of sex development leading to abnormal gonadal development and to unpredictable genital phenotype, growth, and pubertal development.

Case Description: A 2-year-old male presented with a right impalpable testis. Blood karyotype was 46,XY.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis.

Subclinical hypothyroidism in childhood - current knowledge and open issues.

Subclinical hypothyroidism is defined as serum levels of TSH above the upper limit of the reference range, in the presence of normal concentrations of total T or free T. This biochemical profile might be an indication of mild hypothyroidism, with a potential increased risk of metabolic abnormalities and cardiovascular disease recorded among adults. Whether subclinical hypothyroidism results in adverse health outcomes among children is a matter of debate and so management of this condition remains challenging.

Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism.

Objective: To investigate the effect of levothyroxine (L-T4) treatment on early markers of atherosclerotic disease in children with mild idiopathic subclinical hypothyroidism (SH).

Design: Two-year, open, case-control prospective study.

Methods: A total of 39 children, aged 9.

Cardiovascular risk factors in children with long-standing untreated idiopathic subclinical hypothyroidism.

Context: Subclinical hypothyroidism (SH), defined as increased TSH serum levels and normal serum free T4 concentrations, has been associated with an increased risk of coronary heart disease in adults. Data in children and adolescents are scanty.

Objective: The objective of the study was to investigate the clinical and biochemical cardiovascular risk factors in children with mild SH (serum TSH concentrations 4.

Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers.

Subclinical hypothyroidism (SH) is a condition characterized by a mild persistent thyroid failure. The main cause is represented by autoimmune thyroiditis, but mutations in genes encoding proteins involved in TSH pathway are thought to be responsible for SH, particularly in cases arising in familial settings. Patients with the syndrome of TSH unresponsiveness may have compensated or overt hypothyroidism with a wide spectrum of clinical and morphological alterations depending on the degree of impairment of TSH-receptor (TSH-R) function.

Bone health in children with long-term idiopathic subclinical hypothyroidism.

Background: Subclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis.

Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst.

The immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is an autosomal recessive disease presenting with immunodeficiency secondary to hypo- or agamma-globulinemia, developmental delay, and facial anomalies. Centromeric instability is the cytogenetic hallmark of the disorder which results from targeted chromosomal rearrangements related to a genomic methylation defect. We describe a patient carrying a homozygous mutation of the ZBTB24 gene, which has been recently shown to be responsible for ICF syndrome type 2.

Linear growth and intellectual outcome in children with long-term idiopathic subclinical hypothyroidism.

Objective: The treatment of children with subclinical hypothyroidism (SH) is controversial for TSH values between 4.5 and 10 mU/l. The aim of this cross-sectional, controlled study was to evaluate growth and intellectual outcome in children with persistent SH who have never been treated with levothyroxine.

Congenital hypothyroidism and late-onset goiter: identification and characterization of a novel mutation in the sodium/iodide symporter of the proband and family members.

Background: Iodide transport defects (ITDs), rare causes of congenital hypothyroidism (CH), have been shown to arise from abnormalities of the sodium/iodide symporter (NIS). We describe a 16-year-old girl with CH caused by an ITD resulting from a novel mutation of NIS.

Summary: A 16-year-old girl with CH diagnosed by a neonatal screening program received early treatment with L-thyroxine replacement therapy.

Effects of long-term L-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism.

Objective: Patients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy.

Design: The aim of the present case-control study was to evaluate the effects of long-term levothyroxine (l-T(4)) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC).

Methods: Thirty-two young adults with CH aged 18.