Ultrasound-Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview.

BACKGROUND: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic-solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. CONCLUSIONS: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study.

IMPORTANCE: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life.

Raman Spectroscopy as a Potential Adjunct of Thyroid Nodule Evaluation: A Systematic Review.

The incidence of thyroid nodules (TNs) is estimated at 36.5% and 23% in females and males, respectively. A single thyroid nodule is usually detected during ultrasound assessment in patients with symptoms of thyroid dysfunction or neck mass. TNs are classified as benign tumours (non-malignant hyperplasia), benign neoplasms (e.g., adenoma, a non-invasive follicular tumour with papillary nuclear features) or malignant carcinomas (follicular cell-derived or C-cell derived). The differential diagnosis is based on fine-needle aspiration biopsies and cytological assessment (which is burdened with the bias of subjectivity). Raman spectroscopy (RS) is a laser-based, semiquantitative technique which shows for oscillations of many chemical groups in one label-free measurement. RS, through the assessment of chemical content, gives insight into tissue state which, in turn, allows for the differentiation of disease on the basis of spectral characteristics. The purpose of this study was to report if RS could be useful in the differential diagnosis of TN. The Web of Science, PubMed, and Scopus were searched from the beginning of the databases up to the end of June 2023. Two investigators independently screened key data using the terms "Raman spectroscopy" and "thyroid". From the 4046 records found initially, we identified 19 studies addressing the differential diagnosis of TNs applying the RS technique. The lasers used included 532, 633, 785, 830, and 1064 nm lines. The thyroid RS investigations were performed at the cellular and/or tissue level, as well as in serum samples. The accuracy of papillary thyroid carcinoma detection is approx. 90%. Furthermore, medullary, and follicular thyroid carcinoma can be detected with up to 100% accuracy. These results might be biased with low numbers of cases in some research and overfitting of models as well as the reference method. The main biochemical changes one can observe in malignancies are as follows: increase of protein, amino acids (like phenylalanine, tyrosine, and tryptophan), and nucleic acid content in comparison with non-malignant TNs. Herein, we present a review of the literature on the application of RS in the differential diagnosis of TNs. This technique seems to have powerful application potential in thyroid tumour diagnosis.

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022.

Background: Papillary thyroid carcinoma (PTC) often coincides with autoimmune thyroiditis (AIT); whether this association is incidental or causal remains debated. Objective: To evaluate the ultrasonographic, laboratory, and histopathological features of PTC in paediatric patients with and without AIT and its relationship to puberty. Design: A retrospective cohort study. Patients and methods: A retrospective analysis of medical records of 90 patients (69; 76.7% females). The mean age at PTC diagnosis was 13.8 years [range 6-18]. All patients were evaluated ultrasonographically before thyroid surgery. Thyroid nodules were categorised using the European Thyroid Imaging Reporting and Data System (EU-TIRADS PL), and cytopathology was assessed using Bethesda criteria. Neck ultrasound results and thyroid and autoimmune status were correlated with histopathological PTC assessment. Results: The coexistence of PTC and AIT was found in 48.9% (44/90) of patients. The percentage of AIT was increasing with age; AIT was present only in 1/3 of prepubertal, close to 50% in pubertal, and over 60% in adolescent patients. The youngest patients (aged <10 years old) presented more often with goitre and lymphadenopathy and less often with AIT than adolescents (15-18 years of age). There were no differences in TPOAb, TgAb, and TSH levels between the age subgroups. Presurgical TgAb levels were higher than those of TPOAb in the youngest patients. Histopathological analysis revealed that the solid subtype was observed more often in prepubertal children and diffuse sclerosing in children below 14 years of age, whereas the classic subtype dominated in late pubertal. Univariate and multivariate analyses revealed that lymph nodes metastases (LNM) were associated with PTC diameter and fT4 level, whereas extrathyroidal extension with age and angioinvasion with PTC diameter and age. The correlations between age and fibrosis, and the presence of psammoma bodies in malignant tissues were close to significant. We did not observe an association between TSH levels and the presence of autoimmunity and PTC variables. Conclusions: In paediatric patients the natural course of PTC may be less aggressive in adolescent patients than in younger children (especially < 10 years of age). We suggest that pre-operative evaluation of paediatric patients with thyroid nodules could include apart from assessment of thyroid hormones, evaluation of TPOAb, TgAb, and TRAb together with comprehensive neck ultrasonography.

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma - a follow-up study.

Background: Follicular cell-derived thyroid carcinoma represents the vast majority of paediatric thyroid cancers (TCs). Papillary thyroid carcinoma (PTC) accounts for over 90% of all childhood TC cases, and its incidence in paediatric patients is increasing. The objective of this follow-up study was to present the outcome of ultrasound (US) and laboratory monitoring of paediatric patients with autoimmune thyroiditis (AIT) prior to the development of PTC. Patients and methods: This prospective study included 180 children and adolescents (132 females; 73.3%) with a suspicion of thyroid disorder referred to the Outpatient Endocrine Department. The patients were divided into four groups: 1) 28 patients with a mean age of 10.7 [standard deviation (SD), 3.1] y, in whom PTC was detected during the active surveillance of AIT [AIT(+), PTC(+) follow up (F)]; 2) 18 patients with a mean age of 12.8 (SD, 3.4) y, in whom PTC and AIT were detected upon admission (A) [AIT(+), PTC(+) A]; 3) 45 patients with a mean age of 13.0 (SD, 3.4) y, in whom PTC was detected upon admission and AIT was excluded [AIT(-), PTC(+) A]; and 4) an age- and sex-matched control group of 89 patients with AIT and with a mean age of 9.4 (SD, 3.0) y. The analysis included clinical, US, and laboratory assessment results of children on admission (groups 1-4) and during follow-up (groups 1 and 4) in the Paediatric Endocrine Outpatient Department. Results: Upon admission of those in group 1, the US evaluation revealed a hypoechogenic thyroid gland in 12 and an irregular normoechogenic gland in 16 patients. US monitoring revealed an increase in thyroid echogenicity and an increased irregularity of the thyroid structure during the follow-up period of all of the patients from group 1. Such changes were not noticed in group 4. PTC was diagnosed at the mean time of 3.6 y (3 mo-9 y) since AIT confirmation in group 1. The mean maximum PTC diameter as per the US was significantly smaller in group 1 than in groups 2 and 3 [13.2 (10.8) mm vs. 22.2 (12.8) and 22.05 (15.4) mm]. Fewer patients in group 1 were referred to 131I than in groups 2 and 3 (71.4% vs. 94.4 and 93.3%). Interestingly, significant differences were observed in the thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) ratio between groups 2 and 3, as opposed to group 4, at the beginning of observation [15.3 (27.6) and 3.5 (8.8] vs. 0.77 (1.9)]. In group 1, after the follow-up, an increase in the TgAb/TPOAb ratio was observed [1.2 (9.8) to 5.2 (13.5)]. There were no significant differences between groups 1-3 in labeling index Ki67, lymph nodes metastasis, extrathyroidal extension, and angioinvasion. There were no associations between thyroid-stimulating hormone, TgAb, and the extent of the disease. Conclusion: The use of thyroid US focused on the search for developing tumours in the routine follow-up of patients with AIT may not only help in the early detection of thyroid malignancies that are not clinically apparent but may also influence the invasiveness of oncological therapy and reduce the future side effects of 131I therapy. We propose that the repeat evaluation of TPOAb and TgAb warrants further exploration as a strategy to determine TC susceptibility in paediatric patients with AIT in larger multicentre studies.

New insights into thyroid dysfunction in patients with inactivating parathyroid hormone/parathyroid hormone-related protein signalling disorder (the hormonal and ultrasound aspects): One-centre preliminary results.

Objective: This study aimed to present the spectrum of thyroid dysfunction, including hormonal and ultrasound aspects, in a cohort of paediatric and adult patients diagnosed with inactivating parathyroid hormone (PTH)/PTH-related protein signalling disorders 2 and 3 (iPPSD). Methods: The medical records of 31 patients from 14 families diagnosed with iPPSD between 1980 and 2021 in a single tertiary unit were retrospectively analysed. Biochemical, hormonal, molecular, and ultrasonographic parameters were assessed. Results: In total, 28 patients from 13 families were diagnosed with iPPSD2 (previously pseudohypoparathyroidism [PHP], PHP1A, and pseudo-PHP) at a mean age of 12.2 years (ranging from infancy to 48 years), and three patients from one family were diagnosed with iPPSD3 (PHP1B). Thyroid dysfunction was diagnosed in 21 of the 28 (75%) patients with iPPSD2. Neonatal screening detected congenital hypothyroidism (CH) in 4 of the 20 (20%) newborns. The spectrum of thyroid dysfunction included: CH, 3/21 (14.2%); CH and autoimmune thyroiditis with nodular goitre, 1/21 (4.8%); subclinical hypothyroidism, 10/21 (47.6%); subclinical hypothyroidism and nodular goitre, 1/21 (4.8%); primary hypothyroidism, 4/21 (19%); and autoimmune thyroiditis (Hashimoto and Graves' disease), 2/21 (9.6%). Thyroid function was normal in 7 of the 28 (25%) patients with iPPSD2 and in all patients with iPPSD3. Ultrasound evaluation of the thyroid gland revealed markedly inhomogeneous echogenicity and structure in all patients with thyroid dysfunction. Goitre was found in three patients. Conclusion: The spectrum of thyroid dysfunction in iPPSD ranges from CH to autoimmune thyroiditis and nodular goitre. Ultrasonography of the thyroid gland may reveal an abnormal thyroid parenchyma.

Assessment of the function and morphology of the thyroid gland in paediatric patients treated with enzyme replacement therapy due to selected storage diseases - preliminary results of our own research and a review of the literature.

INTRODUCTION: Some storage diseases, caused by a deficiency of a specific enzyme, which results in the systemic accumulation of non-metabolized substances, can be treated with enzyme replacement therapy (ERT), which can protect many organs, including the endocrine system. AIM: The aim of the study was to assess the function and morphology of the thyroid gland in children with storage diseases treated with ERT, and to review the literature. MATERIAL AND METHODS: Eight patients were included in the study: 3 with Fabry disease (age: 17; 9.9; 10 years), 3 with Hunter's disease (12.3; 4.1; 9,3), and 2 with Pompe disease (6.8; 9,5). Thyroid function and morphology were assessed in each patient during ERT, and 4 of them were reassessed 27 months later. RESULTS: One patient with Fabry disease had been treated for hypothyroidism due to autoimmune thyroiditis diagnosed before the study. The remaining patients had normal thyroid tests and negative anti-thyroid antibodies at first and second evaluation; however, in all reassessed patients a decrease in TSH value was noted. Among the remaining patients with Fabry disease, one had normal and a second had heterogeneous echogenicity of the thyroid during first assessment. In the second patient, normalisation of echogenicity was observed at reassessment. Both patients with Pompe disease assessed once had slightly heterogeneous thyroid echogenicity. In 3 patients with Hunter's disease in the first ultrasound examination, no abnormalities were found. In re-evaluation, 2 of them showed heterogeneous thyroid echogenicity. CONCLUSIONS: We conclude that patients with storage diseases should undergo assessment of thyroid function and morphology before and during ERT.

Liver Biochemical Abnormalities in Adolescent Patients with Turner Syndrome

Objective: Elevated liver function tests (LFTs) are common in adult Turner syndrome (TS) patients. Data regarding children and adolescents are lacking. To investigate the prevalence of abnormal LFTs in children and adolescents with TS during several years of observation; to evaluate the potential impact of increased body mass index (BMI) and sex hormone replacement therapy (HRT) on LFTs. Methods: The analysis included 100 girls with TS, aged 4-16 years, all of whom were receiving recombinant human growth hormone therapy. A longitudinal study was conducted which included 81 patients. Results: Mean BMI-standard deviation (SD) score of the subjects was 0.63 (SD: 1.53). Forty-four were being treated with HRT. Elevated LFTs were found in 34% of the patients overall (32% not receiving HRT vs 36% on HRT). The relative risk of increased LFTs was not higher in obese vs normal weight [odds ratio (OR): 0.2; 95% confidence interval (CI): 0.1-0.36, p=0.38 vs OR: 0.16; 95% CI: 0.08-0.3, p=0.1]. HRT did not increase the risk of abnormal LFTs activity (OR: 0.8; 95% CI: 0.5-1.2, p=0.37 vs OR: 0.7; 95% CI: 0.4-1.1, p=0.27). During the follow-up period (mean±SD=4.31±0.82 years), no patient developed overt liver disease. There was no significant increase nor decrease of abnormal LFT frequency in the subsequent years of follow up. Conclusion: Constantly elevated LFTs in TS are common in children and adolescents with TS. However the causes and clinical significance remain unclear. This study suggests that obesity and HRT do not increase the risk of elevated LFTs.

Novel insights in ultrasound evaluation of thyroid gland in children with papillary thyroid carcinoma.

BACKGROUND: The coincidence of autoimmune thyroiditis (AIT) in patients with papillary thyroid carcinoma (PTC) is ranging between 10 and 58% in the general population. MATERIAL AND METHODS: In the present study retrospective ultrasound, clinical and autoimmune assessment of 24 patients diagnosed with papillary thyroid carcinoma between 2000-2016 was performed. RESULTS: The coexistence of PTC and AIT was found in 50% of patients with PTC. Patients were divided into two groups. PTC AIT (+) group involved 12 children at the mean age 14.9 years (range 11-20 years, 9 girls) and PTC AIT (-) 12 children at the mean age 12.9 years (range 7-18 years, 5 girls). Papillary thyroid microcarcinoma (PTMC) was diagnosed in 6 patients (in 5 with AIT). US characteristics of PTC was heterogenous: hypoechogenic with/without increased vascularisation, normoechogenic with halo, with/without microcalcifications. In 70% PTC AIT (+) and in all PTC AIT (-) patients ultrasound analysis revealed that the thyroid tissue of the whole gland was normoechogenic. Local metastases in lymph nodes were found in 40% of PTMC AIT (+). CONCLUSION: Lack of increased vascularization and microcalcifications and presence of``halo`in the nodule does not exclude malignancy. Due to the presence of lymph node involvement in PTMC in all children with PTC total thyroidectomy should be performed with lymph nodes verification.

Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results.

PURPOSE: The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). METHODS: In 14 TS (mean age 13.8), LE (17ß-estradiol, 62.5 µg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17ß-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. RESULTS: There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17ß-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 µIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. CONCLUSION: Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.

Atypical cardiac myxoma in the course of Carney complex in the child. Case Report.

Cardiac tumors in infants and children are rare. Myxomas are the second (after rhabdomyomas) most common primary cardiac tumors in pediatric patients. Cardiac, cutaneous and mucous myxomas are likewise the second most frequent manifestation of the Carney complex, an autosomal dominant multi neoplasia syndrome, which consists of myxomas in different locations, spotty skin pigmentation and endocrine overactivity. We present a case of 13-years-old boy send to our department from a district hospital because of the large tumor in the right atrium discovered in the echo study. On admission he presented discrete signs of Cushing's syndrome and scarse pigmented nevi on the face and trunc. The detailed echo examination showed the large right atrial tumor with features of myxoma, protruding across the tricuspid valve into the right ventricle during diastolic period. Atypical location of cardiac myxoma as well as the signs of Cushing's syndrome suggested Carney's complex. Detailed endocrine studies confirmed the hypothesis. Thus two-step bilateral adrenalectomy was planned. The histopathologic study confirmed primary pigmented nodular adrenocortical disease.

Testicular adrenal rest tumors in congenital adrenal hyperplasia: a case report and literature overview.

OBJECTIVE: In this paper, the etiology, differential diagnosis, and therapy of testicular adrenal rest tumors (TARTs) is presented based on a patient presentation and an overview of the most recent literature concerning this subject. METHODS: Retrospective analysis of the clinical and biochemical data of an 18-year-old male patient diagnosed at the age of 2 weeks with the classic salt-wasting form of congenital adrenal hyperplasia that has been monitored in the pediatric and adolescent outpatient department since the age of 4 years. RESULTS: The results of adrenal hormone tests (17-hydroxyprogesterone, 17-ketosteroids, and pregnanes) had been unsatisfactory, particularly over the previous 5 years. Scrotal ultrasound detected TARTs bilaterally. After increasing the dose of hydrocortisone and introducing dexamethasone, considerable regression of the tumors was noted. CONCLUSION: Lack of complete regression of the lesions is caused by fibrosis and is probably due to decreased sensitivity of adrenocorticotropic hormone and angiotensin II receptors in this tissue.

Adipsic diabetes insipidus in pediatric patients.

OBJECTIVE: To present symptoms, complications and proposition of management protocol in children diagnosed with adipsic diabetes insipidus (aDI). METHODS: Clinical and biochemical analysis of six pediatric patients diagnosed with aDI, four boys aged 5, 13, 16, and 17 y and two girls aged 2.5 and 10 y. The etiology of aDI was germinoma (n = 2), extensive surgery due to optic glioma (n = 1) and astrocytoma (n = 1), congenital brain malformations (n = 1) and complications secondary to bacterial meningitis (n = 1). Two patients had severely impaired vision and two had hemiparesis. RESULTS: In all the patients, loss of thirst reflex was observed. The serum electrolytes in all patients showed sodium concentration from 159 to 176.6 mmol/L with plasma osmolality from above 297 mOsmol/kg. Polyuria was absent in three most severely dehydrated patients on admission. In two patients in whom DDAVP (1-desamino-8-D-arginine vasopressin; Desmopressin) therapy was withdrawn based on lack of polyuria deep venous thrombosis developed. CONCLUSIONS: Lack of polydipsia and polyuria, the key symptoms of diabetes insipidus (DI), may delay the diagnosis of aDI and may lead to severe complications of chronic hyperosmolar status. The fluid intake in patients diagnosed with aDI need to be supervised daily based on calculated constant volume of oral fluids, daily measurements of fluid balance, body weight and sodium levels, especially in patients whose vision is compromised or who are physically unable to take care of themselves.

A case of recurrent labial adhesions in a 15-month-old child with asymptomatic non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Labial adhesions (synechia vulvae) are a relatively common disorder of the external genitalia in prepubertal girls. They usually occur between 3 months and 6 years of age, with a peak between 13 and 23 months of life. In the majority of cases, labial adhesions are asymptomatic and noticed by the parents or a physician during a routine physical examination. Frequently, they cause recurrent urinary tract infections. This report presents the case of a 15-month-old girl with recurrent labial adhesions and urinary tract infections. She was followed-up by a urologist from the age of 3 months, treated topically (estriol cream 1 mg/g and emollients) and surgically. No signs of androgenization were seen apart from advanced bone age. Urinary steroid profile and molecular analysis confirmed the diagnosis of non-classic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency. In the described case, a coincidence of NCCAH and labial adhesion cannot be excluded particularly in view of the resolving of urinary tract infections at the same time as resolving of labial adhesions. However, it seems that in cases of recurrent labial adhesion/synechia that require repeated surgical interventions in view of ineffectiveness of conservative treatment - as it was observed in the presented case - one should consider searching for NCCAH. This may allow not only for the causal treatment of labial adhesions but, above all, NCCAH and, in consequence, the prevention of intensification of virilization, hirsutism, menstrual cycle, and fertility disturbances that are observed starting from puberty.

[Long-term endocrine complications after brain tumor treatment--own experience]. / Odlegle powiklania endokrynologiczne po zakonczeniu leczenia guzów mózgu--doswiadczenia wlasne.

BACKGROUND: Long-term endocrine complications affect approximately 40% of childhood cancer survivors. THE AIM: The retrospective analysis of parameters of the endocrine system function up to 10 years after head radiotherapy (RT) and chemotherapy (CT) due to malignant solid tumor of the central nervous system. MATERIAL AND METHODS: The analysis included 30 patients (15 girls; 15 boys) followed in Endocrine Outpatient Department, University Children's Hospital of Krakow for 1-10 years (mean 5.8 years) after completion of cancer therapy. RESULTS: There was no endocrinopathy in 11 patients (34%), but only five of them were followed for longer than 5 years. A single endocrine disorder was seen in patients (28%), two independent disorders in six (20%), three in three children (10%), and four in two (6.7%). The most common endocrine disorder was growth hormone deficiency (GHD) (13 patients, 46.6%). Primary and secondary hypothyroidism were observed in seven (23%) and two patients (6.7%), respectively, secondary adrenal insufficiency in two (6.7%), hypogonadotropic or hypergonadotropic hypogonadism in seven (23%) and two patients (6.7%), respectively. Obesity without any hormone deficiency was present in five patients (16.6%) patients, in one case, the condition was complicated by glucose intolerance, in four children, by a high level of triglycerides and low HDL cholesterol. CONCLUSIONS: 1. Late endocrine complications after malignant brain tumor treatment affect 66% of patients followed for 1-10 years after completion of RT. That points to the necessity of long-term, regular followup of the patients after cancer treatment. 2. The most common endocrinopathy is GHD, followed by hypothyroidism, hypogonadism and adrenal insufficiency. 3. In patients after head RT and CT in childhood, there is noted secondary obesity, with complications typical for metabolic syndrome.

[Neurofibromatosis type I--the pediatric endocrinologist's point of view]. / Nerwiakowlókniakowatosc typu 1 z punktu widzenia endokrynologa dzieciecego.

AIM OF THE STUDY: A retrospective analysis of endocrine disorders in patients with neurofibromatosis type I consulted in the Children's University Hospital of Krakow in the period 2007-2010. MATERIAL AND METHODS: The analysis included 60 patients (33 girls, and 27 boys) aged 1.2-32 years, mean 11.6 years. The patients were followed up by many health care professionals: neurologists (EEG), neurosurgeons (CT, MRI), ophthalmologists, psychologists, ENT specialists, anthropologists (the assessment of body height and weight), geneticists, endocrinologists and gynecologists (the assessment of puberty according to Tanner scale, diagnostics of short stature, precocious puberty), and cardiologists (echo-cardiography). RESULTS: In the analyzed group of 60 patients, 46 were consulted by geneticists, 20 by endocrinologists, 19 by neurologists and cardiologists. The imaging of the central nervous system (CNS) was performed in 37 patients. Twenty-two patients presented with familial NF-I, 13 with sporadic NF-I, and in 25 patients, the family history was unavailable. Growth disorders were present in 27.7% of patients (13/47) that were referred to the anthropometric assessment. Short stature (height < or = (-) 2 SD) was recognized in 9/47 of children (19.1%). Tall stature (> (+) 2 SD) was recognized in 4/47 of patients (8.5%). All of the patients with tall stature presented with central precocious puberty (PD). Precocious puberty was also recognized in two children with normal stature. In all cases of PD, optic chiasm gliomas were recognized. Generally, organic CSN disorders were detected in 24 patients (63.2%). MRI revealed optic chiasm gliomas in 8 patients, 4 presented with gliomas of one or two optic nerves, 10 presented with hyperintensive areas on T2-weighted images, without enhancement after contrast injection, that may suggest the diagnosis of hamartoma of the CNS, and 2 with hydrocephaly. CONCLUSIONS: 1. The most common disorders of the somatic development revealed in NF-I patients are growth disorders: short stature and tall stature caused by central precocious puberty. 2. In view of the incidence of endocrine disorders in patients with NF-I, the authors suggest an endocrine consultation in each case of NF-I.

[The impact of the 4-year human recombinant growth hormone treatment on growth, body composition and bone mineral density in patients with isolated growth hormone deficiency and multihormonal pituitary insufficiency]. / Wplyw 4-letniego leczenia ludzkim rekombinowanym hormonem wzrostu na wzrastanie, sklad ciala oraz gestosc mineralna koscca u dzieci z izolowana somatotropinowa niedoczynnoscia przysadki i wielohormonalna niedoczynnoscia przysadki.

BACKGROUND: In addition to stimulating bone growth in length, human recombinant growth hormone (rhGH) significantly affects in a direct and IGF-I-mediated manner body composition (body fat/lean body mass ratio) and skeletal maturation in vitro and in vivo. The direct role of rhGH on bone mineralization and its effect on bone mineral density is controversial. AIM: To compare growth and body composition, bone mineral density (BMD) and bone mineral content (BMC) in prepubertal children with isolated growth hormone deficiency (GHD) and congenital multihormonal pituitary deficiency (MPD), including MPD resulting from the PROP-1 gene mutation. MATERIAL AND METHODS: The study included 53 children (36 boys and 17 girls) aged 8.4 +/- 3.2 years with diagnosed GH deficiency. The subjects were divided into three groups. Group 1 consisted of patients with MPD resulting from the PROP-1 gene mutation: 14 children (8 girls and 6 boys) aged 6.4 +/- 2.1 years, Group 2 included children with MPD resulting from causes other than the PROP-1 gene mutation: 21 patients (5 girls and 16 boys) aged 9.6 +/- 3.9 years, while Group 3 represented children with GHD: 18 subjects (4 girls and 14 boys) aged 8.6 +/- 2.5 years. All the children were clinically and biochemically euthyreotic. The patients were assessed auxologically every three months. Their bone age was evaluated every year. Puberty stages were determined according to Tanner. BMI was calculated in keeping with the equation: kg/m2. Bone densitometry and body composition were determined by DEXA (DPX-IQ Lunar) prior to initiation of rhGH substitution and at yearly intervals in the course of rhGH treatment. RESULTS: Prior to commencement of rhGH substitution, the height of the PROP [+] patients was the lowest of all groups, with statistical significance demonstrated when comparing the above children to the GHD group (PROP [+]: -3.3 SD; PROP [-]: -2.8; GHD: -2.7 SD). Growth analysis in the three groups of patients showed a statistically significant improvement in each group, with the strongest effect in the PROP [+] group; the respective height increase in particular groups was: PROP [+]: 2.8 SD; PROP [-] 1.6 SD; GHD 1.9 SD. After 4-year rhGH substitution, patients with MPD PROP [+] and PROP [-] demonstrated an increase of BMC by 585.9 g and 350.2 g, respectively; no significant increase was observed in the GHD group. Prior to treatment, all the groups showed a comparable decrease of lumbar spine BMD (BMD LS): Z-score PROP [+] (-) 2.5 SDS; PROP [-] (-2.8) SDS; GHD (-) 2.0 SDS. In subsequent years of treatment, the BMD LS values were within normal range, i.e. above (-) 2.0 SD. A statistically significant increase of BMD LS by (+) 1.1 SD was noted in the PROP [-] patients. In all the groups, the mean total BMD values were within normal range, i.e. above (-) 2.0 SD prior to initiation of rhGH substitution and in subsequent years of follow-up. Prior to commencement of rhGH substitution vBMDLS SDS of the PROP [+] patients was the lowest of all groups, with statistical significance demonstrated when comparing the above children to the GHD group (PROP [+]:(-)2,8 +/- 1,6; PROP [-]:(-)1,9 +/- 1,8; GHD: (-)1,9 +/- 2,3 SD. After 4-year rhGH substitution lowest values of vBMDLS SDS were found also in PROP[+]: (-)1,6 +/- 1,3 SD, ans subsequently PROP[-]: (-)0,9 +/- 1,0 and SNP: (-)0,7 +/- 1,8 SD. Body fat percentage prior to rhGH substitution was the highest in the PROP [+] patients and the lowest in the GHD group: PROP [+]: 28%, PROP [-]: 26%, GHD: 20%, with the difference between PROP [+] and GHD being statistically significant. During all study period all children remained prepubertal. CONCLUSIONS: 1) Patients with MPD and the PROP1 gene mutation are characterized by a shorter stature, lower BMD and lower lean body mass as compared to MPD patients without PROP1 mutation and to GHD patients. 2) In comparison to children with GHD, rhGH substitution in patients with MPD exerted a more favorable effect on their growth, BMD and body composition.

Biological effects of thyrotropin receptor activation on human orbital preadipocytes.

PURPOSE: Thyrotropin receptor (TSHR) expression is upregulated in the orbits of patients with Graves ophthalmopathy (GO), most of whom have TSHR-stimulating antibodies. The authors investigated the biological effects of TSHR activation in vitro in adipose tissue, the site of orbital TSHR expression. METHODS: Activating mutant TSHR (TSHR*) or wild-type (WT) was introduced into human orbital preadipocytes using retroviral vectors. Their proliferation (Coulter counting), basal cAMP accumulation (radioimmunoassay), and spontaneous and peroxisome proliferator-activated receptor (PPARgamma)-induced adipogenesis (quantitative oil red O staining) were assessed and compared with those of nonmodified cells. QRT-PCR was used to measure transcripts of CCAT/enhancer binding protein (C/EBP)beta, PPARgamma, and lipoprotein lipase (LPL; early, intermediate, and late markers of adipogenesis) and for uncoupling protein (UCP)-1 (brown adipose tissue [BAT]). RESULTS: Expression of TSHR* significantly inhibited the proliferation of preadipocytes and produced an increase in unstimulated cAMP of 200% to 600%. Basal lipid levels were significantly increased in TSHR* (127%-275%) compared with nonmodified (100%) or WT-expressing (104%-187%) cells. This was accompanied by 2- to 10-fold increases in early-intermediate markers and UCP-1 transcripts (2- to 8-fold); LPL was at the limit of detection. In nonmodified cells, adipogenesis produced significant increases in transcripts of all markers, including LPL (approximately 30-fold). This was not the case in TSHR*-expressing cells, which also displayed 67% to 84% reductions in lipid levels. CONCLUSIONS: TSHR activation stimulates early differentiation (favoring BAT formation?) but renders preadipocytes refractory to PPARgamma-induced adipogenesis. In neither case did lipid-containing vacuoles accumulate, suggesting that terminal stages of differentiation were inhibited.

[Complete gonadal dysgenesis 46, XY in a 16-year-old girl with a female phenotype--case report]. / Czysta dysgenezja gonad 46, XY u 16-letniej fenotypowej dziewczynki--przedstawienie przypadku.

We present a case of a 16-year-old girl, who attended the Endocrinology Outpatient Clinic of the University Paediatric Hospital in Kraków, because of lack of breast development and primary amenorrhea. Pubic hair development was normal. Baseline hormonal blood tests indicated a primary gonadal lesion (hypergonadotropic hypogonadism). Ultrasonography examination revealed bilateral streak gonads in ovarian localisation. Uterus was present. The karyotype was male: 46, XY. Gonadectomy was performed due to risk of gonadoblastoma development in streak gonads. Based on the histology of the removed gonads the final diagnosis of complete gonadal dysgenesis 46, XY was established. After the gonadectomy hormonal replacement therapy was introduced. Authors emphasise the importance of considering in each case of delayed puberty in teenage girls the possibility of complete gonad dysgenesis 46, XY. The diagnosis can be established only on the support of a reliable knowledge of male sex differentiation physiology.

[Partial gonadal dysgenesis in a 12-year-old girl--diagnostic and therapeutic difficulties]. / Czesciowa dysgenezja gonad u 12-letniej dziewczynki -- trudnosci diagnostyczno-lecznicze.

The authors present a 12-year-old girl who was seen in the out-patient Endocrinology Clinic, University Children's Hospital of Cracow, with the preliminary diagnosis of androgen insensitivity syndrome, presenting with progressing virilisation, breast underdevelopment and dysmorphy. Pubarche was normal. Gynecological examination revealed ambiguous external genitalia. On ultrasound examination homo genic gonad-like structures without follicles were seen, but no uterus was present. Basic hormonal studies indicated hypogonadotropic hypogonadism. The child was diagnosed as partial gonadal dysgenesis 46, XY. A gonadectomy was performed due to the 30-40% risk of gonadoblastoma development characteristic for such cases, and estrogen substitution followed after the surgery. The authors stress the necessity of including partial gonadal dysgenesis and partial androgen insensitivity syndrome in the differential diagnosis of delayed puberty. In both the above mentioned syndromes the clinical features are similar but the management differs. The authors stress the importance of establishing the cause of the condition and further management prior to discharging the neonate. The ultimate sex must allow the patient to best fulfill his/her psychosocial role in society and reduce the psychological trauma.