Clinical Toxicity of Acute Overdoses With L-Thyroxin in Children.

OBJECTIVES: L-Thyroxine ingestion is rarely seen in children; here, we report our experience of it. This study describes the clinical characteristics and laboratory findings of acute L-thyroxine ingestion in children. METHODS: This retrospective study enrolled patients treated for L-thyroxine ingestion at Kayseri Teaching Hospital between September 2013 and September 2016. Clinical characteristics and laboratory findings are described. Ethical approval was not obtained because the study was retrospective. RESULTS: The incidence of L-thyroxine ingestion was 0.07% to 1.2% per year. There were 14 patients. Twelve patients were asymptomatic, but 2 (14.2%) exhibited tachycardia and hypertension. Thyroid hormone levels were elevated in 3 patients (21.4%). Eleven patients did not require medical treatment (78.4%); 3 did. No serious complication or death was observed. CONCLUSIONS: Acute ingestion has a benign course. Serious complications are uncommon but may appear several hours or days after ingestion; therefore, patients with L-thyroxine ingestion should be followed closely for 2 weeks.

Adherence to growth hormone therapy: results of a multicenter study.

OBJECTIVE: To evaluate the adherence to growth hormone (GH) therapy and identify the influencing factors and outcomes in children. METHODS: A total of 217 GH-naïve patients in 6 pediatric endocrinology clinics were enrolled in the study. Structured questionnaires were filled out and patients were evaluated at the initiation and 3rd, 6th, and 12th months of therapy. Patients were categorized into 4 adherence segments based on percentage of doses omitted at each evaluation period, classified as excellent if 0%, good if 5%, fair if 5 to 10%, and poor if > 10%. RESULTS: There was a decrement in adherence to GH therapy during the study period (P = .006). Patients who showed excellent and good adherence to therapy had better growth velocity and growth velocity standard deviation scores (SDSs) (P = .014 and P = .015, respectively). A negative correlation between growth velocity SDS and number of missed injections was also observed (r = -.412; P = .007). A positive correlation between delta insulin-like growth factor-1 (IGF-1) SDS and growth velocity was demonstrated (r = .239; P = .042). IGF-1 levels were significantly higher in patients who showed excellent and good adherence to therapy (P = .01). Adherence was better in boys than in girls (P = .035), but adherence rates were not associated with age, cause of GH treatment, socioeconomic status, person who administered the injections, type of injection device, or GH product. CONCLUSION: Poor adherence to GH therapy was common in our group of patients and was one of the factors underlying suboptimal growth during therapy. Before considering other problems that can affect growth, clinicians should confirm good adherence to therapy.

Prevalence of hyperthyrotropinemia in obese children before and after weight loss.

BACKGROUND: Obesity is a worldwide epidemic. In recent years, increasing attention has been focused on thyroid function in obesity. OBJECTIVES: To establish the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents, and identify the relationship between TSH levels and other metabolic and hormonal variables before and after weight reduction. MATERIALS AND METHODS: We evaluated 150 obese subjects (aged 3-17 years) for anthropometric, biochemical, metabolic and hormonal variables. Measurements were taken at baseline and, in a subgroup of children with hyperthyrotropinemia, after a 6-month intervention program based on exercise, behavior therapy, and nutrition education. RESULTS: At baseline, 23 participants (15.3 %) had hyperthyrotropinemia, and 21 of these patients completed the weight reduction intervention. Among these 21 patients, 14 had substantial weight loss and a significant decrease in TSH and free T3 levels. CONCLUSION: We conclude that TSH and T3 levels are significantly increased in childhood obesity; in most cases, however, these increases cannot be elucidated by thyroid autoimmunity or iodine deficiency. If thyroid disorders are excluded beforehand, an elevated TSH with normal thyroid hormone levels in obese children seems rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated TSH levels. In this context, thyroid hormone alterations in obesity suggest an adaptation process.

Iatrogenic Cushing syndrome due to nasal steroid drops.

Iatrogenic Cushing syndrome may occur as an undesirable outcome of high-dose glucocorticoids treatments. This may also cause hypothalamus-hypophysis-adrenal axis suppression. While this situation may be caused more frequently with oral and topical glucocorticoid therapy, iatrogenic Cushing syndrome in childhood, caused by steroid-containing nasal drops, is a rare event. Hereby, we present a baby who developed iatrogenic Cushing syndrome induced by long-term use of steroid-containing nasal drops for choanal atresia. In conclusion, the serious side effects of the nasal drops should have been explained to the family, and their long-term use should have been refrained.

Thyroid nodules in children and adolescents: a single institution's experience.

OBJECTIVE: The aims of this study were to analyze the role of fine-needle aspiration biopsy (FNAB) in the management of pediatric thyroid nodules and to analyze the malignancy risk of thyroid nodules by studying the association between autoimmune thyroiditis and thyroid cancer. METHODS: We conducted a retrospective study on 111 patients with thyroid nodules diagnosed in childhood or adolescence. FNAB was performed in 46 participants with thyroid nodules after ultrasonography (US). Cytology diagnoses were categorized as insufficient, benign, suspicious, and malignant. Clinical and surgical follow-up data were obtained from medical records. The clinical correlation and accuracy of FNABs were evaluated. RESULTS: The family history was positive in four patients. Forty-six patients had positive antithyroid antibodies and an inhomogeneous hypoechogenic US pattern. One patient had previous neck irradiation history. Eighty-six patients (%77.5) were euthyroid. All patients underwent US examination. The FNAB results of the 46 patients were 29 (63%) benign cases, 7 (15%) insufficient, and 10 (22%) suspicious patients. Malignancy was not reported at all. A repetition of FNAB in two benign cases, which were diagnosed with papillary carcinoma during followup, reported these cases as suspicious. Ten patients with suspicious FNAB results underwent surgery because of increases in the size of the nodules; two patients were diagnosed with papillary carcinoma. In this study, the prevalence of malignancy was 4.5% in patients with thyroid nodules. CONCLUSION: In this study, the importance of FNAB in the diagnosis and follow-up of thyroid nodules in childhood has been observed, and risk factors, such as history of familial thyroid carcinoma, radiotherapy to the neck at younger ages, suspicious cytological findings, and increased nodular sizes during follow-up in cases with Hashimoto thyroiditis have been correlated with increased thyroid carcinoma malignancy risk.

Assessment of the 21-hydroxylase deficiency and the adrenal functions in young females with Turner syndrome.

There are few reports of an association between Turner syndrome (TS) and 21-hydroxylase deficiency. However, this association is more frequent in some populations. The aim of this study was to evaluate the incidence of 21-hydroxylase deficiency in patients with TS in our population. 21-hydroxylase deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis, Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP), dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated. Patients with increased 17OHP responses in the stimulation test also underwent 21-hydroxylase gene analysis. The mean age was 14.6 +/- 4 (2.6-22.4); 37 patients were on growth hormone (GH) treatment. Nine patients were at prepubertal stage, whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP, and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic analysis. In other cases, peak 17OHP levels were < or = 6 ng/mL. The mean peak 17OHP was 2.62 +/- 1.48 (1.19-7.5) ng/mL, the cortisol level was 37.6 +/- 8.43 (23.9-56.2) microg/dL and the DHEAS was 135.2+/- 87.3 (15-413) microg/dL. The increased mean basal and peak cortisol levels (20.5 +/- 10.2 and 37.6 +/- 8.4 microg/dL) were remarkable findings. Whereas basal cortisol was above 20 microg/dL in 38.7% of patients, exaggerated results up to 56.2 microg/dL were obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were not correlated with the presence of puberty, chromosome structure, gonadal steroid use, obesity or growth hormone use. This trial suggested that 21-hydroxylase deficiency was not common among patients with TS in our population. Adrenal function should be assessed, at least in the presence of clitoral enlargement in patients with TS, particularly if their karyotype does not contain a Y chromosome.

A pediatric Conn syndrome case.

Conn syndrome, which is rarely encountered in children, is characterized by increased aldosterone, low renin level, and arterial hypertension. Severe complications, such as impaired vascular smooth muscle function secondary to increased aldosterone, endothelial dysfunction, deterioration of left ventricular functions, acute effects on the cardiovascular system, and proteinuria, may be observed. We present a case of primary aldosteronism in a patient who has been followed up for approximately 2 years. A 15-year-old girl complained of headache lasting for approximately 1.5 years, which was diagnosed as severe hypertension. All of her systemic examinations were normal other than the hypertension. Primary aldosteronism was diagnosed on the basis of hypokalemia and alkalosis accompanied by plasma renin activity of 3.9 ng/mL/h and an aldosterone level of 1007 pg/mL (normal: 40-480). Left adrenalectomy was performed because a 10x12x12 mm adenoma was detected on abdominal magnetic resonance imaging. Although aldosterone levels returned to normal values after the surgery, antihypertensive treatment was continued because of the persistent hypertension. As the 24-h ambulatory blood pressure values of the patient were normal at 10 months after the operation, the treatment was stopped, and she was followed up for 15 months without any treatment. Since then, she has been normotensive.

Seizure due to somatostatin analog discontinuation in a case diagnosed as congenital hyperinsulinism novel mutation.

The most common reason for refractory hypoglycemia in newborns is congenital hyperinsulinism. We report a girl with congenital hyperinsulinism due to novel homozygous mutation (c.2041-25 G>A; aberrant splicing mutation) in the ABCC8 gene encoding SUR1 and during somatostatin analog (octreotide) discontinuation developed by nonhypoglycemic seizures. The newborn (birth weight of 3,750 g) was referred to our clinic because of hypoglycemic seizures at 4 h postnatal. On admission, blood glucose was 24 mg/dL and intravenous glucose infusion was started. The patient's insulin level was 27 mIU/mL during the hypoglycemic period. Phenobarbital (5 mg/ kg/day) was added because of short-acting generalized clonic seizures. Although the patient received high doses of diazoxide, esidrex, and octreotide approximately for 2 months, hypoglycemic episodes continued. Then the patient had near-total pancreatectomy, and pathology confirmed a diffuse form of congenital hyperinsulinism. There was homozygous mutation in the ABCC8 gene encoding SUR1, which confirmed the diagnosis of autosomal recessive congenital hyperinsulinism. During octreotide discontinuation, the patient developed non-hypoglycemic seizures, which were controlled by restarting the previous doses. In the light of in vitro and in vivo studies on antiepileptic effects of somatostatin, we believe that seizures in our case have developed secondary octreotide discontinuity.

Mild and severe congenital primary hypothyroidism in two patients by thyrotropin receptor (TSHR) gene mutation.

Congenital hypothyroidism (CH) is the most commonly encountered endocrinological birth defect, with an incidence of approximately 1 in 3000-4000 live births. It could be sporadic or familial as well as goitrous or non-goitrous. Inactivating mutations of TSHR , which is one of the genes responsible for non-goitrogenic congenital hypothyroidism, are mostly inherited autosomal recessively and result in a wide clinical spectrum owing to the extent of receptor function loss. Here, we report detailed clinical features of two CH cases with TSHR mutations. The first case was diagnosed before the initiation of the national screening program and had a severe clinical phenotype associated with a homozygous inactivating TSHR mutation (P556R), whereas the second case was diagnosed after the introduction of the national screening program and showed a mild clinical presentation and carried another homozygous missense mutation (P162A) in the TSHR gene. We compared the clinical features of our cases with those of previously reported patients with TSHR mutations to enhance the genotype/phenotype correlations between these mutations and corresponding clinical phenotypes.

The cause of severe hypercalcaemia resistant to pamidronate treatment: subcutaneous fat necrosis with no visible skin lesion.

Subcutaneous fat necrosis (SCFN) is an uncommon cause of neonatal hypercalcaemia. It is usually seen in neonates after a complicated delivery within the first month of life. While uncommon, hypercalcaemia can be fatal. It is characterised by red-purple plaques in fatty points along with firm subcutaneous nodules. Rarely, SCFN may cause severe hypercalcaemia with no visible skin lesion. In this rare case, we report severe infancy hypercalcaemia without characteristic skin lesion on first physical examination, unresponsive to hydration, diuretic, prednisolone and standard dose of pamidronate treatment. As timely diagnosis and treatment are so important, this complication should be kept in mind even in such clinical presentations.

Thiamine-responsive megaloblastic anemia syndrome with atrial standstill: a case report.

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an uncommon autosomal recessive disorder. The disease is caused by mutations in the gene, SLC19A2, encoding a high-affinity thiamine transporter, which disturbs the active thiamine uptake into cells. Major features include megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Cardiac malformations with conduction defects and/or dysrhythmias, have also been described in some patients. To our knowledge, only 13 TRMA patients with cardiac defects have been reported. Here, we describe the first case of TRMA syndrome with atrial standstill, probably caused by a 2 base-pair deletion in exon 4 (1147delGT) of the gene SLC19A2.

A case of Langerhans cell histiocytosis with thyroid involvement.

Thyroid involvement with Langerhans cell histiocytosis (LCH) is very rare. We report here the case of a 15-year-old female patient with LCH affecting the thyroid gland. She was referred to the department of pediatric endocrinology for secondary amenorrhea. Prior to the diagnosis of LCH, the patient had symptoms of diabetes insipidus (DI) and amenorrhea. The mean time from symptom onset to diagnosis was 2 years. On physical examination the patient had grade 2 goiter, and ultrasound showed bilateral multiple hypoechoic nodules and thyroid heterogeneity. Biochemical analysis indicated central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) demonstrated a mass lesion involving the hypothalamus, which appeared iso- to hypo-intense on T2-weighted images and had an intense postcontrast enhancement on T1-weighted images. Nodular goiter coinciding with a hypothalamic mass suggested LCH, and an excisional biopsy was performed. Histological evaluation of the thyroid gland revealed extensive involvement by LCH, and this was confirmed by immunohistochemical analysis showing S-100 protein and CD1a positive Langerhans cells that were weakly positive for CD68. LCH should be considered in the differential diagnosis of a diffusely enlarged firm and irregular thyroid gland and posterior or anterior pituitary dysfunction.

Acute renal failure due to severe hypercalcemia and nephrocalcinosis treated with two doses of pamidronate in an infant with Williams-Beuren syndrome.

Bastug F, Nalçacioglu H, Bas VN, Tekatli-Çelik B, Çetinkaya H, Yel S. Acute renal failure due to severe hypercalcemia and nephrocalcinosis treated with two doses of pamidronate in an infant with Williams-Beuren syndrome. Turk J Pediatr 2018; 60: 210-215. Infantile hypercalcemia has been reported in 15% of infants and children with Williams-Beuren syndrome (WBS) and has generally mild clinical symptoms. However, the need for pamidronate treatment in a few infants with severe hypercalcemia associated with WBS has been reported in literature. Many disorders, such as primary hyperoxaluria, associated with nephrocalcinosis can lead to renal failure, but there are only a few reports in infants with WBS who have decreased renal function and nephrocalsinosis. We present a 23-month-old girl with WBS (confirmed with fluorescent in situ hybridization probes) who presented with acute renal failure with severe symptomatic hypercalcemia and nephrocalcinosis, which responded to two infusions of pamidronate.

Effects of L-thyroxine treatment on heart functions in infants with congenital hypothyroidism.

BACKGROUND: Impaired heart functions in newborns with hypothyroidism should be reversed by levothyroxine substitution therapy. The aim of the study was to investigate heart functions with congenital hypothroidism (CH) in newborns and changes after levothyroxine substitution therapy, measured with tissue Doppler echocardiography and conventional echocardiography. METHODS: The study included 30 neonates with CH and 34 healthy controls. Echocardiography were performed at baseline, 2nd week and 6th month of therapy. RESULTS: Heart systolic function was normal. Mitral E velocities and mitral E/A ratios were significantly lower in patients at baseline. Tei indices were significantly higher in patients and a significant negative correlation was detected between free thyroxine levels and Tei indices.When early and late post-treatment echocardiography findings are compared, a non-significant difference was detected. CONCLUSIONS: Neonates with CH may exhibit systolic and diastolic heart dysfunction, which can be reversed by early L-T4 substitution treatment. The Tei index index should be measured in addition to conventional echocardiography.

Bone mineral density and bone metabolic markers' status in children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem disorder characterized by progressive manifestations, which is inherited in an autosomal dominant manner. The majority of patients with NF1 experience a diffuse, significant reduction in bone mass over time, with osteoporosis, osteopenia in the absence of severe scoliosis, or gross bone deformities. This study aimed to determine the bone mineral density (BMD) status, evaluate bone metabolism, and to determine the relevant factors in children with NF1. METHODS: The study population included 33 pediatric NF1 patients (20 males and 13 females). Bone metabolic markers, such as total calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin D, the urinary calcium/creatine ratio were measured. In addition, BMD was measured at both the lumbar spine (LS) and the femoral neck in all the patients. RESULTS: All the patients had a low 25-OH vitamin D level, but it was significantly lower in the females than in the males (p<0.009). Overall, 18.2% of the patients had skeletal abnormalities. The lumbar Z-score was ≤2 in 21.2% of the patients, whereas the femoral neck Z-score was ≤2 in 9.1%. The urinary calcium/creatine ratio was significantly higher in the female than in the male patients (p<0.027). In all, six patients had skeletal abnormalities. CONCLUSIONS: It is widely known that bone mineral metabolism markers and BMD are significantly affected in NF1 patients; however, the present study did not identify any effective parameters that could be used to predict skeletal abnormalities, or diagnose early osteoporosis and osteopenia in pediatric NF1 patients.

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing.

BACKGROUND: Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing. METHODS: A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ-ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing. RESULTS: We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A, one has HNF4A, one has HNF1B, two have NEUROD1, one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations. CONCLUSIONS: This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.

Diverse Genotypes and Phenotypes of Three Novel Thyroid Hormone Receptor-α Mutations.

CONTEXT: Recently several patients with resistance to thyroid hormone (RTH)-α due to T3 receptor-α (TRα) mutations were identified. The phenotype of these patients consists of varying degrees of growth impairment, delayed bone, mental and motor development, constipation, macrocephaly, and near-normal thyroid function tests. OBJECTIVE: The objective of the study was to describe the clinical phenotype of three new families with RTHα and thereby gain more detailed knowledge on this novel syndrome. DESIGN, SETTING, AND PARTICIPANTS: RTHα was suspected in three index patients from different families. Detailed clinical and biochemical assessment and imaging and genetic analyses were performed in the patients and their relatives. In addition, functional consequences of TRα mutations were investigated in vitro. RESULTS: We studied 22 individuals from three families and identified 10 patients with heterozygous TRα mutations: C380fs387X, R384H, and A263S, respectively. The frame-shift mutation completely inactivated TRα, whereas the missense mutations produced milder defects. These mutations were associated with decreasing severity of the clinical phenotype: the patient in family 1 showed severe defects in growth, mental, and motor development, whereas the seven patients in family 3 had only mild clinical features. The most frequent abnormalities were anemia, constipation, and a delay in at least one of the developmental milestones. Serum free T3 ranged from high-normal to high and serum free T4 and rT3 from normal to low. TSH levels were normal in all patients. CONCLUSIONS: This large case series underlines the variation in the clinical phenotype of RTHα patients. RTHα should be suspected in subjects when even mild clinical and laboratory features of hypothyroidism are present along with high/high-normal free T3, low/normal free T4, and normal TSH.

Diabetic euglycemic ketoacidosis in newly diagnosed type 1 diabetes mellitus during Ramadan fasting.

Real euglycemic diabetic ketoacidosis [DKA; blood glucose <200 mg/dL (11.1 mmol/L)] is rare, and long-lasting starvation conditions due to intervening diseases in type 1 diabetes mellitus patients may also cause it. Euglycemic DKA is also reported in insulin-dependent diabetics with depression, alcoholics, glycogen storage diseases, and chronic liver disease apart from pregnant cases. This case report is presented to emphasize the importance of evaluation of acid-base state, urine glucose, and ketone values at the application in all newly diagnosed type 1 diabetic patients with normal glucose levels by defining euglycemic DKA that resulted from long-lasting starvation during Ramadan fasting in a newly diagnosed 14-year-old male patient.

Hypopituitarism and Legg-Calve-Perthes disease related to difficult delivery.

Legg-Calve-Perthes (LCP) disease is characterized by idiopathic avascular osteonecrosis of the epiphysis of the femur head. The main factor that plays a role in the etiology of the disease is decreased blood flow to the epiphysis. Many predisposing factors have been suggested in the etiology of LCP disease, and most have varying degrees of effects. Here we present the case of a boy aged 4 years and 10 months with complaints of short stature and a diagnosis of multiple hypophyseal hormone deficiency, in whom LCP disease and difficult birth-related pituitary stalk interruption syndrome were identified by anamnesis. The present case revealed that LCP disease and hypophyseal hormone deficiency could be secondary to difficult birth and that LCP disease could be secondary to insulin-like growth factor 1 deficiency. Additionally, to the best of our knowledge there is no published case on the relation between LCP disease and insulin-like growth factor 1 deficiency. Therefore, we believe that this case is worthy of presentation.