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.

Causes and consequences of abandoning one-stage bilateral adrenalectomy recommended in primary pigmented nodular adrenocortical disease--case presentation.

We present a 7-year-old girl with a 2-year history of decelerated growth rate and cushingoidal obesity, upon admission presenting with fixed hypertension. Cyclic hypercortisolemia with inhibited baseline and post-CRH stimulation ACTH level pointed to primary adrenal hypercortisolemia. Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) showed normal adrenal glands. 131J-labeled cholesterol scintiscan showed a weak but slightly more expressed tracer uptake in the left adrenal gland. Cushing syndrome concomitant with isolated primary pigmented nodular adrenocortical disease (PPNAD) was diagnosed. After hypotensive pretreatment, a left adrenalectomy was performed, resulting in normalization of corticoadrenal function, blood pressure, Cushing features and growth rate. Histopathology confirmed PPNAD. In the course of infection, corticoadrenal function showed absence of adrenal reserve, and adrenal crisis. Hydrocortisone (HC) therapy, followed by HC supplementation was introduced. Four years later, a contralateral adrenalectomy was performed and total HC supplementation was introduced. Causes and consequences of abandoning one-stage bilateral adrenalectomy recommended in PPNAD are reviewed.

[Neurological disorders in patients with hypoparathyroidism]. / Zaburzenia neurologiczne u pacjentów z niedoczynnoscia przytarczyc.

BACKGROUND: The term hypoparathyroidism refers to a group of disorders in which a relative or absolute deficiency of PTH leads to hypocalcemia and hyperphosphatemia. THE AIM OF THE STUDY: Was to evaluate clinical symptoms in patients with hypoparathyroidism during normocalcemic period and to try to establish its etiology (electrolyte imbalance, organic central nervous system lesions, coincidence of tetany and epilepsy). MATERIAL AND METHODS: The analysis included a group of 14 patients with hypoparathyroidism: 3 boys and 11 girls, aged from 12 months to 31 years (median 16.11 years), with duration of the disease 12 months to 26 years (median 10.9 years). In all the patients, the diagnosis was confirmed based on history, physical examination, results of biochemical and hormonal laboratory tests, radiological and neurological examinations. All the patients were followed by endocrinology specialists. Low phosphorus diet, calcium, magnesium, active vitamin D supplementation and management of other endocrine disorders were employed. RESULTS: In 9 patients, pseudo-hypoparathyrodism was diagnosed; of this number, in 8 children, type Ia Albright syndrome was confirmed. Five patients were diagnosed as true hypoparathyroidism, two girls in this group were found to have autoimmune hypoparathyroidism as a component of the autoimmune polyglandular syndrome type 1, 2 others were diagnosed in infancy as congenital hypoparathyroidism and 1 girl had true hypoparathyroidism as a component of Kearns-Sayre syndrome. Five patients were referred to neurological department with epilepsy suspicion. In the medical history, 9 patients had generalized epileptic seizures, moreover, 1 girl manifested absence attack and balance disturbances. In 3 patients, EEG demonstrated changes typical of generalized seizure activity. In 5 patients on anti-epileptic management, additional calcium and active vitamin D treatment was initiated, allowing for achieving seizure remission. CT of the head and pituitary gland showed calcification foci in the central nervous system in 9 patients. Five patients of the eight individuals with Albright syndrome showed mild or moderate mental retardation confirmed by psychological testing. CONCLUSIONS: 1. Hypoparathyroidism leads to functional and morphological CNS changes. 2. Restoring metabolic balance through administration of calcium and active vitamin D preparations may obliterate the need for anti-epileptic treatment. 3. Calcification foci in the central nervous system seem to be associated with the duration of hypoparathyroidism. 4. No correlation has been observed between the extent and location of calcification foci and neurological abnormalities. 5. Hypoparathyroid patients with calcification foci in CSN require long-term multidisciplinary medical management and neurophysiological, imaging and neuropsychological monitoring.

[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.

[Disorders of lipid metabolism in adolescents with simple obesity]. / Zaburzenia metabolizmu lipidów u mlodziezy z otyloscia prosta.

BACKGROUND: Obesity affects approximately 45 millions of children worldwide. Some of them present with secondary dyslipidemia that leads to premature atherosclerosis. AIM OF THE STUDY: 1) Assessment of the frequency and type of dyslipidemia in obese adolescents. 2) An attempt at defining risk factors of atherogenic lipid profile in obese adolescents. MATERIAL AND METHODS: In 146 (84 girls/62 boys) obese (mean BMI SDS 4.95, 95% CI 4.62-5.29) adolescents (age 10-18, mean 14.7 years), the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglicerydes (TG) were measured. Atherogenic dyslipidemia was defined as a high TG level with a concomitant low HDLc level. Standard oral glucose tolerance test was performed with the assessment of fasting and after 120' post-load of 75 g of glucose and insulin levels; the insulin resistance index HOMA-IR was calculated. RESULTS: The mean values of the lipid fractions were in normal ranges: TC 4.64 mmol/L (95% CI 4.48-4.8), LDLc 2.86 mmol/L (95% CI 2.73-2.99), TG 1.4 mmol/L (95% CI 1.3-1.5), and HDLc 1.16 (95% CI 1.1-1.2). However, in 50.69% of the patients (45.24% girls and 58.06% boys), elevated levels of TC, LDLc, and TG were observed respectively in 23.29%, 17.81% and 37.67%, and low HDLc in 15.07% of patients. A total of 10.96% of the patients presented with coexistence of a low HDLc and a high TG. In 26.7%, dyslipidemia was followed by arterial hypertension. There was a reverse correlation between a low HDLc value and BMI SDS [R (-) 0.22, p < 0.05] and not with TC, LDLc, and TG. The relative risk of abnormal lipid profile occurrence was higher in obese patients with insulin resistance (OR 1.72; 95% CI 0.8-3.4; p = 0.12), being significant only for boys (OR 3.67; 95% CI 1.1-12.1; p = 0.03). There was a reverse correlation between fasting insulin level, HOMA-IR and HDLc [R (-) 0.2; p < 0.05; R (-) 0.2; p < 0.05) respectively], as well as TG (R 0.26 ; p < 0.05; R 0.26; p < 0.05, respectively), and between post-load insulin level and TG (R 0.24; p < 0.05). CONCLUSIONS: 1) Lipid disorders occur in about one-half of obese adolescents, of which 10% presents with atherogenic lipid profile. 2) One of the most important risk factors of atherogenic lipid profile occurrence is insulin resistance, especially in boys. The severity of the obesity (BMI-SDS) is of lesser importance.

Bilateral slipped capital femoral epiphysis as first manifestation of primary hyperparathyroidism in a 15-year-old boy.

ABSTRACT: Primary hyperparathyroidism (PHP) in children is a rare condition and has a very dynamic course with nonspecific symptoms, what complicates the diagnosis and delays PHP treatment. CASE PRESENTATION: A 15-year-old boy was admitted to the Orthopedic Ward with the diagnosis of juvenile bilateral slipped capital femoral epiphysis and valgus deformities. Gait disturbances, limb pains and valgus knee deformities, polyuria, polydipsia and weight loss, have been increasing for 8 months. Despite the hypercalcemia found in laboratory tests and bone destruction demonstrated in computed tomography of the hips, orthopedic correction was performed. In histopathological examination -brown bone tumors. The PTH concentration was determined (PTH - 589.1 pg/ml; (N: 10-60) and the child was referred to the Department of Pediatric Endocrinology, where severe hypercalcemia (Ca - 4.07 mmol/l, N: 2.2-2.84) and hypophosphatemia (P - 0.68 mmol/l; N: 0.95-1.75) and adenoma of the left lower parathyroid gland was diagnosed. Forced diuresis, loop diuretics and pamidronic acid were used to obtain normocalcemia. The complications of hypercalcemia were excluded; diagnostic management excluding multiple endocrine neoplasia type 1 and 2a (MEN 1 and MEN 2A) syndrome were performed. The child was referred to the Department of Endocrinological Surgery, where the adenoma of the left inferior parathyroid gland was resected. CONCLUSIONS: 1) Patients with PHP should be diagnosed of the condition based on clinical symptoms. In patients with specific symptoms, it is necessary to determine serum Ca levels, especially prior to the surgical procedures. 2) In each case of PHP, determinations should be made of blood PTH, Ca and P and detection of MEN 1 and MEN 2A syndromes. 3) Patients with hyperparathyroidism require management of multiorgan complications of hypercalcemia. 4) Following surgical treatment of parathyroid adenoma, long-term endocrinological follow-up is necessary.

[The role of a pediatric endocrinologist in diagnostics and therapeutic management of anorexia nervosa--own experiences and review of literature]. / Rola endokrynologa dzieciecego w diagnostyce i leczeniu jadlowstretu psychicznego--doswiadczenia wlasne i przeglad pismiennictwa.

INTRODUCTION: Anorexia nervosa and bulimia nervosa are counted among psychosomatic diseases, whose incidence has been rapidly increasing in the last decades. To date, the etiology, diagnostic and therapeutic management of eating disorders have not been uniformly determined. The objective of the study is determination of the role of a pediatric endocrinologist in diagnostics and management of eating disorders. MATERIAL: In the years 1992-2007 in Department of Pediatric and Adolescent Endocrinology Chair of Pediatrics, Polish-American Institute of Pediatrics, Collegium Medicum, Jagiellonian University in Krakow, Poland were hospitalized 164 patients with suspected anorexia nervosa, aged 9-20 years, 150 girls, and 14 boys. All girls were included in psychological and dietetic treatment. Additionally, in group of 36 girls, the 3-years observation of bone mineralization changes was performed. METHODS: The indications for hospitalization included the assessment of nutritional status, particularly electrolyte imbalance, cardiovascular complications and nutritional treatment. II. Procedure included on department: 1) Correction of general children's state. 2) Monitoring of cardiovascular system disorders. 3) Nutritional treatment. 4) Differential diagnosis. III. Prevention and treatment of late complications was performed in group of 36 girls. In this group, every 6 months were evaluated: body mass index, duration of secondary amenorrhea, serum sex hormone, IGF-I and cortisol levels and 24-hour urine cortisol. Spine densitometry in the AP projection was performed every 12 months, using a Lunar unit (DEXA). The pharmacological treatment of osteoporosis was introduced in girls with duration of secondary amenorrhea lasted for more than 6 months, with decreased bone mineralization BMD < (-) 1SD and body mass deficit < 20%. 16 girls which did not presented disorders of bone mineralization, or refused treatment have not got the pharmacological treatment, while in 20 girls the pharmacological therapy (calcium and vitamin D3 supplementation and hormonal treatment - Estraderm TTS and Provera 5 mg) was provided. RESULTS: Anorexia nervosa was diagnosed in 150 cases, bulimia in 6 cases, in 2 children was diagnosed celiac disease, in 2 patients adrenal insufficiency, in 1 girl myasthenia, in 1 girl diabetes mellitus type 1, in 1 boy hypothalamo-pituitary tumor and in 1 boy psychosis was diagnosed. The nutritional improvement was evaluated in group of 36 girls, which continued treatment in time 3 years. At the beginning of the observation period the mean value of the body mass index (BMI) was 15.95 kg/m2, and after 36 months of the treatment the mean BMI value was 20 kg/m2. Before the treatment one patient was still menstruated despite her body mass loss, 8 girls were pre-menarche, and the remaining 27 patients had secondary amenorrhea of the mean duration of 11.14 months. In the initial period of the follow-up, all the anorectic patients demonstrated a decreased bone mineral density. Before treatment the median Z score in the entire experimental group was (-)1,2 SD whereas after 3 years of treatment value of Z score decreased by 0,5 SD in group of 16 girls without the pharmacological treatment and increased by 0,5 SD in 20 girls on pharmacological treatment. The significant, negative correlation between secondary amenorrhea and Z score value was observed. CONCLUSIONS: The role of a pediatrician in therapeutic management of eating disorders is intervention in life-threatening conditions, treatment of acute complications, differential diagnosis, nutritional treatment, prevention and management of late complications. Because of etiology and special way of treatment the management of anorexia nervosa should have been taken by psychiatrist. The duty of endocrinologists and gynecologists is the late complications treatment, such as an amenorrhea and osteoporosis.