Central European Annals of Clinical Research

We present the case of a child with mild axial hypotonia and episodes of persistent hyponatremia and hyperkalemia early in life, followed by an asymptomatic long period. During the present hospital admission, dysregulation of the adrenal gland function and detection of two missense variants in NR0B1 (nuclear receptor subfamily 0 group B member 1) gene state with high probability the diagnosis of congenital adrenal insufficiency. Management include substitution therapy and food supplementation with salt with good outcome. Full article

Short stature is a common cause for addressing the endocrinologist. Growth hormone deficiency is estimated to occur in 1:4000 to 1:10,000 of small stature cases [¹]. Identifying and treating these children is of high importance given the psycho-social implication of small stature. I present the case of a male teenager ages 15 years 10 months old who responded well to treatment, achieving the target genetic stature. Full article

Prader-Willi syndrome (PWS) is the most common syndromic cause of life-threatening obesity, scoliosis and obstructive sleep apnea (OSA) being the major concerns for these patients. We report the case of a five year-old girl with PWS admitted for growth hormone therapy. Initially she had medium-severe OSA that required tonisllectomy and severe scoliosis. At six months follow-up after intitation of therapy, she had a good response with better height and body fat index, OSA improvement, but progression of the scoliosis severity. With this case report we underline that, while growth hormone therapy in PWS patients is efficient and not directly related to scoliosis and OSA exacerbation, careful monitoring during therapy is recommended. Full article

Hypothyroidism is a worldwide medical problem, most of the cases being related to primary causes like thyroid autoimmune background or multinodular goiter. A particular form of thyroid hormone insufficiency of the central type is related to Dyke–Davidoff–Masson (DDM) syndrome, which is a severe condition associating hemicerebral hypoplasia or even atrophy, a consequence of a brain injury during the fetal period of time or the first years of childhood. In addition to neurological damage, pituitary function may be affected, requiring hormone replacement. Full article

Osteoporosis is reflected by low bone mineral density (BMD) at central Dual-Energy X-ray Absorptiometry (DXA) as well as clinical complications like low-trauma or spontaneous fractures. While typical primary osteoporosis is menopause-related, among the secondary causes of osteoporosis, osteogenesis imperfecta (OI) is listed for children, teenagers and adults. Underlining more than 17 mutations, and a heterogeneous clinical presentation, decreased BMD is associated with multiple fractures and impaired peak bone mass with lifelong effects. Full article

Background and Aims The World Health Organization (WHO, www.who.int) and European Association for the Study of Obesity (EASO, www.easo.org) have suggested to substitute the term Obesity with Adiposity Based Chronic Disease (ABCD) in the 11th International Classification of Diseases ICD­11. The term ABCD is believed to be more precise based on three dimensions—etiology, degree of disease and health risk. The intention is to improve the diagnostic and therapeutic algorithms as well as the relationship between healthcare professionals and society [1]. Aim The aim of the present study is to make an overview of the current data for epidemiology, diagnosis, treatment and prevention of childhood obesity. The current data for the prevalence of severe obesity among primary school children in 21 European countries show differences among the countries: from 1 in 5 to 1 in 3 obese children [2]. Childhood obesity is an extremely heterogeneous disorder and demands proper diagnostic evaluation for every individual patient. Early onset and severe obesity may be caused by rare mutations of the genes associated with appetite or energy control and rare syndromes. Once diagnosed, treatment options are available [3]. The most prevalent type of obesity is polygenic and is called “simple obesity”. It is extremely heterogeneous in genetic susceptibility. The new approach of quantifying inherited susceptibility has led to the validation of the genome­wide polygenic score (GPS) [4]. The treatment options for childhood obesity are still limited and the success rate is inconsistent [5]. The success rate of childhood obesity treatment and prevention of severe obesity is highly dependent on timely referral to specialist care. Full article

Background and Aims Pituitary stalk interruption syndrome (PSIS) is characterized by the presence of a thin or absent pituitary stalk in association with a hypoplastic or aplastic anterior pituitary or an ectopic neurohypophysis [1,2]. The phenotype associated with PSIS has a high incidence of various combinations of hormonal deficiencies, sometimes associated with extra-pituitary birth defects [1]. The aim of our study is to illustrate the heterogeneity of PSIS through a complete description of the clinical, biological and imagistic differences between our cases. Case Reports We describe two rare pediatric cases. The first case was a 6-year-old boy admitted to our department with polyuro-polydipsic syndrome and underdeveloped external genitals. He had a history of neonatal micropenia and a family medical history of panhypopituitarism and midline malformations. Physical examination revealed normal stature (height: 117 cm, −0.4 SDS), obesity (BMI: 25.2 Kg/mp, over 97th percentile), micropenia (stretched penile length: 3 cm) and non-palpable testes. Initially, his urine output was 5000 mL/24 h, with a low urine specific gravity of 1005–1010, and no increase after water deprivation test, with an appropriate response after desmopresin administration. He presented normoglycemia. Serum gonadotropin (FSH, LH) and testosterone levels were low, with no response after GnRH-analogue stimulation test. IGF-1 levels were low-normal. His Copeptin value was decreased. Pituitary MRI showed anterior pituitary hypoplasia, absence of the pituitary stalk and neurohypophysis. The second case was a 4-year-old girl referred to our service for growth retardation. She had a history of neonatal prolonged jaundice and intermittent seizures, for which she was prescribed phenobarbital for 2 years. Her physical examination described short stature (height: 90.5 cm, −3.3 SD), underweight (BMI: 15.87 Kg/m2, 15–25th percentile), head dysmorphic features: medial epicanthal fold, depressed nasal bridge, anteverted nares, ogival palate. She had a bone age of 2 years. The initial evaluation diagnosed severe GH deficiency, and during the next 3 years of follow-up she developed ACTH, TSH and FSH-LH deficiencies. MRI examination indicated anterior pituitary hypoplasia, absence of pituitary stalk and ectopic neurohypophysis. Discussion Central diabetes insipidus is rarely reported in patients with PSIS (0–4%) [1,3]. Although GH deficiency was found almost ubiquitous in PSIS, our first patient had no growth retardation. Normal linear growth despite abnormal GH secretion was also reported [4]. Neonatal cholestasis was linked to ACTH deficiency, which can also be a cause of recurrent hyponatremia [1]. There were no signs of ACTH deficiency or hyponatremia in our second patient in the neonatal period. Few reports showed cases of PSIS that were diagnosed with acute epileptic seizures accompanied by hyponatremia [5]. The rapidly progressive evolution to combined pituitary deficiency observed in PSIS cases [4] with neonatal features was also recognized in our patients. Conclusions The phenotype associated with PSIS can be highly heterogeneous. It is important to increase the awareness of PSIS, especially in the neonatal period when the features of PSIS can be easily overlooked. We also emphasize the importance of patient follow-up as an essential part of an adequate management. Full article

Background Laron syndrome (growth hormone insensitivity) is a rare autosomal recessive condition characterized by severe short stature with postnatal onset usually (1), particular facial features and hypoglycemia in childhood, and type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity in adulthood (2), caused by growth hormone receptor (GHR) anomalies (insensitivity). It is estimated that there are 350 people with this condition worldwide (3). The growth hormone receptor mutation prevents the stimulating effects of growth hormone, inducing insulin-like growth factor-1 (IGF1) deficiency. Treatment with recombinant IGF1, the only treatment option which can improve final height (4), is not available for all patients. Aim Present the clinical outcomes of a Laron syndrome patient untreated and on hormonal substitution treatment. Case Report A 18-year-old girl with Laron syndrome diagnosed at the age of 2 years and 10 months, based on the clinical feature of severe short stature (height—63 cm; −8.24 SDS, standard deviation score), particular facial features (protruding forehead, saddle nose, large eyes, sparse and thin silky hair, and high-pitched voice), small hands and feet, and sweating and hypotonic episodes, especially in the morning. The endocrine growth axis assessment revealed an elevated growth hormone concentration (>40 ng/mL; 0–8 ng/mL) and very low serum IGF-1 levels (<25 ng/mL; NV = 75–175), respectively, and delayed bone age (9 months—Greulich and Pyle). The genetic assay showed a homozygous pathological variant (c476T > A L141X) in the 6 exon of the GHR gene. The growth velocity without hormonal substitution was low at 0.23 cm/month (14.5 cm/63 months). After 15 months (between 8 years 1 month and 9 years 4 months) of IGF1 (mecasermin) treatment, the growth velocity increased to 0.53 cm/month, the girl’s height increased from 77.5 cm (−8.55 SDS) to 85.6 cm (−7.94 SDS). After IGF1 treatment discontinuation, height velocity fell to 0.22 cm/month. At the age of 17 years and 2 months, hormone replacement therapy with mecasermin was resumed up to 18 years. The patient also had associated pubertal delay; thelarche started at the age of 15 and progressed slowly. The final height of the patient was 117 cm. In addition, she has developed focal epilepsy, obesity, and depression. Conclusions Early diagnosis and hormone substitution therapy may reduce the clinical consequences of complications, improving the prognosis. Full article