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.

Comparison of clinical characteristics of a pediatric cohort with combined pituitary hormone deficiency caused by mutation of the PROP1 gene or of other origins.

The most commonly identified genetic cause of combined pituitary hormone deficiency (CPHD) is PROP1 gene mutations. The aim of the study was to compare selected clinical features of patients with CPHD caused by variants of the PROP1 gene (CPHD-PROP1) and patients with inborn CPHD of other etiology (CPHD-nonPROP1). MATERIAL AND METHODS: The retrospective analysis included childhood medical records of 74 patients (32 female) with CPHD, including 43 patients (23 female) with the mutation in the PROP1 gene. RESULTS: Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with the following: significantly higher median birth weight (0.21 vs. - 0.29 SDS, p = 0.019), lower growth velocity within 3 years preceding growth hormone administration (- 2.7 vs. - 0.8 SDS, p < 0.001), higher mean maximal blood concentration of growth hormone within the stimulation process (1.2 vs. 1.08 ng/mL, p = 0.003), lower TSH (1.8 vs. 2.4 µIU/mL, p < 0.001), significantly lower prolactin concentrations (128 vs. 416.3 µIU/mL, p < 0.001), and less frequent typical signs of hypogonadism at birth in boys (n = 6; 30% vs. n = 12, 54%, p < 0.001). Secondary adrenal insufficiency was less frequent in CPHD-PROP1 (20 vs. 25 cases, p = 0.006) and occurred at a later age (13.4 vs. 10.4 years). MRI of the pituitary gland in CPHD-PROP1 revealed a small pituitary gland (21 cases), pituitary gland enlargement (eight cases), and one pituitary stalk interruption and posterior lobe ectopy, while it was normal in nine cases. CONCLUSION: Patients with the PROP1 mutations present a clinical picture significantly different from that of other forms of congenital hypopituitarism. Certain specific clinical results may lead to the successful identification of children requiring diagnostics for the PROP1 gene mutation.

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.

The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective: Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment. Methods: Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH. Results: The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels. Conclusion: These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.

An Attempt to Assess the Impact of Pandemic Restrictions on the Lifestyle, Diet, and Body Mass Index of Children with Endocrine Diseases-Preliminary Results.

BACKGROUND: Home isolation during the coronavirus 2019 (COVID-19) pandemic lockdown strongly impacted everyday life, affecting, in particular, eating habits and everyday activity. The aim of this study was to analyze the impact of the pandemic on behaviors and subsequent changes in body mass index (BMI) in children from Southern Poland. METHODS: The study included 206 participants (104 females and 102 males) with a complete analysis of 177 participants (96 females and 81 males) with a mean age of 12.8 ± 2.6 years admitted to three pediatric endocrinology clinics (Rzeszów, Kraków, and Katowice) due to simple obesity, type 1 diabetes mellitus, somatotropin pituitary deficiency on growth hormone replacement therapy, and other endocrine and metabolic disorders between June and September 2020. The study used a self-prepared questionnaire regarding eating habits, physical activity, screen time, and sleep before and during the lockdown. Anthropometric measurements were performed under clinical settings twice (before the pandemic in January-March 2020, and in June-September 2020). RESULTS: During the lockdown, BMI z-scores increased over the whole group, especially in obese children (0.073 ± 0.18, p = 0.002). The number of children who declared low and high physical activity of more than 60 min per day declined from 41.2% and 18.6% to 31.1% and 6.2% (p = 0.03 and p < 0.001), respectively; sleep times over 8 h increased (46.9% vs. 60.4% p = 0.007); screen times over 5 h daily increased (14.7% to 46.9%, p < 0.001). Eating habits did not change significantly. CONCLUSIONS: Daily physical activity and sleep levels were affected by the pandemic leading to the increase of BMI, especially in obese patients with endocrine disorders. During the COVID-19 pandemic, forward-thinking strategies must be developed to prevent childhood obesity.

Cyclic Cushing's Disease in the Prepubertal Period-A Case Report and Review of Literature.

Background: Cyclic Cushing's disease (CD) has been described in about 15% of adult patients with CD. In the pediatric population, diagnosis of CD is rare and cyclic presentations of the disease are not adequately understood or described. Moreover, prepubertal patients usually do not present with the typical signs and symptoms of CD, which can obscure or delay diagnosis. In this paper, we report a case of cyclic CD in a prepubertal age girls whose etiology was a pituitary corticotropinoma. Case presentation: A Caucasian 7.8 year old girl was admitted to pediatric endocrinology for the evaluation of short stature and prior obesity. The patient remained overweight despite significant lifestyle modifications, resulting in 6 kg weight loss during the prior 6 months. The physical exam was notable for precocious adrenarche and thelarche, but difficult to differentiate from steatomastia. Hypothalamo-pituitary-adrenal axis diagnostics, including single diurnal excretion of urinary cortisol, morning ACTH, and serum cortisol levels, were all within normal limits, and MRI of the pituitary gland showed no deviations at this time. Because of the clinical suspicion of cyclic hypercortisolemia, she was referred to our outpatient clinic for follow-up. After 6 months, the patient returned with rapid weight gain, accompanied by nocturnal anxiety, exacerbation of depressive behavior, insomnia and excessive sweating, and was readmitted to the ward for testing. Standard diagnostics confirmed CD and repeat MRI at 8.6 years old showed a microadenoma of 3 × 4 mm in the right side of the anterior pituitary gland. Histopathologic examination described an atypical, densely-granulated pituitary corticotroph adenoma with Ki-67 expression above 3%. Conclusion: Cyclic presentations of CD in the prepubescent age group could cause difficulties in diagnosis because of atypical signs and symptoms, which can be absent in the remission phase. Decreases in height percentiles and velocities obtained from the growth chart, as well as fluctuations in weight, and signs of androgenization can allow the clinician to suspect cycling CD in prepubertal patients. Confirmation of cyclic CD diagnosis is only possible during periods of relapse (hypercortisolemic state) and should be investigated according to the current diagnostic standard.

The impact of thyroid function on the occurrence of metabolic syndrome in obese children and adolescents.

INTRODUCTION: Thyroid axis abnormalities are common in obese patients. Their contribution in the development of metabolic obesity complications remains unclear. AIM OF STUDY: To assess the influence of thyroid axis dysfunction on the occurrence of metabolic obesity complications. MATERIAL AND METHODS: A cross-sectional review of the thyroid function in 100 obese patients (59 girls and 41 boys, mean age 13.5 years) with alimentary obe-sity (mean standardised body mass index [BMI SDS] in boys 4.175 and girls 4.723) complicated by metabolic syndrome (MS) diag-nosed on the basis of the IDF 2006 criteria (MS, 25 patients) and uncomplicated (75 patients). TSH, fT4, fT3 thyroid peroxidase anti-bodies (TPOAb), and thyroglobulin antibodies (TGAb) were assessed in a single fasting blood sample. RESULTS: There was no case of overt thyroid disease within the whole analysed group. There were no significant differences in mean TSH, fT4, and fT3 levels in patients with and without MS (2.7 µIU/ml vs. 3.0 µIU/ml, 14.5 vs. 14.0 pmol/l, and 5.6 vs. 6.2, respectively; p > 0.05). In the MS group only two patients (8%) presented with a TSH level above the upper limit of the normal range; in the group without MS elevated TSH was noticed in 18 (24%) patients. The maximal value of TSH (10.44 µIU/ml) was noticed in one boy without MS. Positive TPOAb and/or TGAb were present in 11% of all patients: two patients (8%) with MS and nine (12%) without MS. CONCLUSIONS: Isolated increased TSH level is common in obese adolescents, although there is no correlation between TSH, fT3, and fT4 levels and BMI SDS value. Isolated increased TSH level is not associated with the occurrence of MS in obese adolescents. The occurrence of asymptomatic autoimmune thyroiditis (AITD) in obese adolescents is more common than in the general population.

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.

A case report of severe panhypopituitarism in a newborn delivered by a women with Turner syndrome.

Turner syndrome (TS) is a congenital disease caused by absence or structural abnormalities of sex chromosomes resulting in gonadal dysgenesis. Spontaneous pregnancies occur in 2-8% of patients, especially with mosaic kariotypes, however they are associated with increased risk of poor outcome both for mother and fetus. We report a 4-day-old male infant delivered by women with mosaic TS who was admitted to the pediatric intensive care unit and presented with severe panhypopituitarism as the early manifestation of pituitary stalk interruption syndrome (PSIS). To the best of our knowledge this is the first report of severe panhypopituitarism in a newborn borne by women with TS.

The first description of metyrapone use in severe Cushing Syndrome due to ectopic ACTH secretion in an infant with immature sacrococcygeal teratoma. Case Report.

Cushing syndrome due to ectopic secretion of ACTH in infants is rare. The treatment of choice is radical resection of the tumour in combination with pre-operative chemotherapy using steroidogenesis inhibitors if necessary. If radical surgery is not possible, palliative treatment of hypercortisolemia is recommended. The most frequently used drug in infants is ketoconazole. Experience with the use of metyrapone is poor. We report an 8-month-old female infant with congenital immature sacrococcygeal teratoma secreting AFP, beta hCG and ACTH who had undergone non-radical resection of the tumour mass and was receiving standard risk chemotherapy (vinblastine, bleomycin, and cisplatin). The infant initially presented at the age of 6 months with ACTH-dependent Cushing syndrome (cortisol and ACTH level 325 ng/mL, 112 pg/mL respectively). Treatment with ketoconazole was initiated with a dose of 600 mg/day. Due to its ineffectiveness metyrapne was added in increasing dosages, up to 1,500 mg/day. In addition the schema of chemotherapy was changed (adriamycin, bleomycin, carboplatin), which resulted in normalization of cortisol levels and blood pressure. There were no metyrapone side effects during the treatment period. We can conclude that treatment with metyrapone at a dose of 1500 mg/day might be effective and safe in infants with Cushing syndrome.

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.

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.