Should we routinely assess hypothalamic-pituitary-adrenal axis in pediatric patients with Prader-Willi syndrome?

Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.

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.

Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader-Willi Syndrome: A Polish Multicentre Study.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.

Diversity of Pathological Conditions Affecting Pituitary Stalk.

Pituitary stalk lesions (PSL) are a very rare pathology. The majority of conditions affecting the infundibulum do not present with clinically apparent symptoms, what makes the diagnosis difficult. The recognition might be also complicated by the non-specific and transient characteristics of hormonal insufficiencies. In our study, we retrospectively analysed demographic, biochemical, and clinical long-term data of 60 consecutive, unselected adult patients (34 women and 26 men) with PSL diagnosed in the Department of Endocrinology, Jagiellonian University in Krakow. The diagnosis of PSL were categorized as confirmed, probable, or undetermined in 26, 26 and 8 patients, accordingly. Given the possible aetiology congenital, inflammatory, and neoplastic stalk lesions were diagnosed in 17, 15 and 20 patients, accordingly. In eight cases the underlying pathology remained undetermined. The most common pituitary abnormality was gonadal insufficiency diagnosed in 50.8% of cases. Diabetes insipidus was detected in 23.3% of cases. In 5% of patients the pituitary function recovered partially over time. Stalk lesions were extensively discussed in the context of the current literature. Based on the published data and our own experience a diagnostic algorithm has been proposed to help physicians with the management of patients with this challenging condition.

Correlation of Genotype and Perinatal Period, Time of Diagnosis and Anthropometric Data before Commencement of Recombinant Human Growth Hormone Treatment in Polish Patients with Prader-Willi Syndrome.

Genotype-phenotype correlation in patients with Prader-Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age-group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

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.

The effects of growth hormone therapy on the somatic development of a group of Polish children with Silver-Russell syndrome.

OBJECTIVE: Silver-Russell Syndrome is both clinically and genetically a heterogeneous syndrome. Among the most important dysmorphic features of this condition are: a triangular shaped face with a small mandible, a prominent frontal eminence, a thin vermilion border with downward-pointing lip corners, clino- and brachydactyly of the 5th fingers as well as body asymmetry. The most well-known genetic mutations in this syndrome are: the 11p15 epimutation (20-60% patients) and the maternal uniparental chromosome 7 disomy present in 7% to 15% of patients. Children with SRS have severely impaired physical growth - intrauterine and after birth. This, together with the aforementioned dysmorphic features, forms the main diagnostic criteria. MATERIAL AND METHODS: The study group consisted of 12 children treated with growth hormone, aged 2 to 17 (8.9±4.0 years), therein, all of whom met the phenotype diagnostic criteria by Wollmann and Price. The effects of growth hormone therapy on somatic development of these children are also presented. RESULTS: Height and weight improved as a result of growth hormone treatment, but the effects were significantly worse than in children with IUGR. Children from the study group presented also a smaller an improvement in growth velocity than children from the control group, but the difference was statistically insignificant. CONCLUSIONS: Growth hormone therapy accelerates the growth of children with SRS but to a smaller extent than the growth of children born with intrauterine growth retardation without dysmorphic features.

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.

A ten-year observation of somatic development of a first group of Polish children with Silver-Russell syndrome.

OBJECTIVE: Silver-Russell syndrome is heterogeneous both clinically and genetically. The best known genetic aberrations existing in this syndrome are an 11p15 epimutation, present in 20-60% patients, and a maternal uniparental chromosome 7 disomy (7-15%) (upd(7)mat). Children with SRS suffer from physical growth impairments - intrauterine and after birth. MATERIAL AND METHODS: The study group consisted of 38 children aged 2 to 17 (x=8.9 ± 4.0 years). These children had undergone a genetic analysis in search for the 11p15 epimutation and the upd(7)mat. Somatic growth was also analysed in terms of birth parameters and postnatal BMI, weight and height. The aforementioned parameters were compared in a subgroup of children with the genetic aberrations and with a control group of children born with IUGR. RESULTS: In the study group a mean weight SD on birth was -3.41 ± 1.22, the birth height was -1.25 ± 2.08 SD and a head circumference of -3.56 ± 1.93 SD. No significant differences were noted between the SRS study group and the control group in reference to weight and head circumference (p>0.05). Such difference was, however, seen in birth height. Children with 11p15 epimutation had significantly lower weight and height at birth, but a significantly larger head circumference than children without this genetic aberration. When analysing further development of children with SRS, a significantly smaller height SD, body mass and BMI was observed, compared with children from the control group. CONCLUSIONS: Children with SRS present impaired somatic development compared to children with IUGR, and these with a genetic aberration develop worse.

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.

Atypical Clinical Presentation of ACTH-Dependent Cushing's Syndrome in a Patient Treated with Retinoic Acid.

OBJECTIVE: The leading signs and symptoms of Cushing's syndrome (CS) in adolescents, which depend on the duration and the severity of hypercortisolemia, are: a decrease in growth velocity with an increase in body weight, redistribution of fat tissue (round face), and less commonly, acne due to hyperandrogenization. A widely used antiacne drug, retinoic acid, can change the clinical presentation of CS and delay the diagnosis. METHODS: We report an atypical presentation of adrenocorticotropic hormone (ACTH)-dependent CS in a patient treated with retinoic acid due to severe acne. RESULTS: Three months after the discontinuation of retinoic acid treatment (at a dose of 40 mg daily for 6 months, with a 4 month break and then for an additional 6 months), a 17.5-year-old male presented with short stature (-3.0 SD), muscle weakness, difficulty concentrating, insomnia, and depressed mood. Body weight (body mass index, 22 kg/m2), fat tissue distribution, pubertal status (testicular volume equal to 20 mL, pubarche V, axillarche present), and blood pressure were normal, and the patient's bone age was equal to his chronologic age. His bone mineral density was decreased (Z-score, -3.5 SD). The morning serum cortisol level was normal (8:00 AM, 171.9 ng/mL) and did not decrease in the evening (8:00 PM, 178.9 ng/mL) or after 1 mg of dexamethasone (100.4 ng/mL). The patient's urinary free cortisol was elevated on 3 occasions (274.5, 217.3, and 253.7 µg/day). Increased ACTH levels in the morning (97.5 to 141.1 pg/mL) and postcorticoliberine (577.6 pg/mL) pointed to ACTH-dependent CS. A magnetic resonance imaging scan of the pituitary gland confirmed the presence of a microadenoma. CONCLUSION: Retinoic acid treatment may alter the clinical presentation of ACTH-dependent CS and consequently delay the diagnosis.

[Clinical symptoms at the diagnosis of the craniopharyngioma]. / Objawy kliniczne przy rozpoznaniu czaszkogardlaka.

INTRODUCTION: Craniopharyngioma can cause neurological, ophthalmological and endocrine signs and symptoms. AIM OF THE STUDY: Retrospective analysis of symptoms accompanying diagnosis of craniopharyngioma in children. MATERIAL AND METHODS: 10 children and adolescents, 3.75-14.08 years old, median 8.96, treated in our centre in the years 1992-2010, with diagnosis of craniopharyngioma, were included into the study. In the analysis clinical symptoms at the moment of diagnosis, before surgery treatment were taken into consideration. Data from medical histories, physical examination, auxological data, biochemical and hormonal parameters were analyzed. RESULTS: Among 10 patients, 9 had headaches, 4 had experienced vomiting, 2 had symptoms of cranial hypertension, 6 had vision disorders, 8 had endocrine disorders. A decrease of growth rate was observed in 5 children (among 7 with previous anthropometric data), diabetes insipidus in 2, gain of body weight and delayed puberty in 1, and secondary hypothyroidism in 1 patient. Endocrine disorders appeared on average 13 months before diagnosis of craniopharyngioma. Among them the earliest was the decrease of growth rate - on average 23 months before the diagnosis, and the latest diabetes insipidus - 2 months before it. The most frequent symptom - headaches appeared 2 months before the diagnosis. CONCLUSIONS: 1. Endocrine symptoms are early symptoms of craniopharyngioma, which usually appear before neurological, and ophthalmological disorders. 2. Craniopharyngioma may be a cause of growth disorders in children and adolescents, therefore a detailed analysis of height data on growth charts in pediatric patients is very important for the diagnosis.

Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects.

BACKGROUND/AIMS: Defects of the PROP1 gene are the most prevalent genetic cause of combined pituitary hormone deficiency. Previous observations in affected patients have shown pituitary size ranging from hypoplasia to overt pituitary mass and evolution of size over the lifespan. METHODS: We evaluated pituitary size and morphology in PROP1-mutation carriers who originated from Central and Eastern Europe. We analyzed 112 pituitary magnetic resonance imaging (MRI) scans from 82 patients (42 males) aged 2.5-72.7 (median 16.6) years from 60 kindreds. RESULTS: Among the 120 independent PROP1 alleles, the most prevalent mutations were delGA301/302 (99 alleles) and delA150 (13 alleles). Median pituitary height at first MRI was 4.7 mm (range 1.0-20.7) and median volume was 127.6 mm(3) (range 7.5-3,087.0). Pituitary size did not differ between sexes and did not correlate with hormonal phenotype, but significantly decreased with increasing age. However, evaluation of individual values suggested a biphasic mode with increasing volume during childhood, peak in adolescence, and subsequent regression in adulthood. CONCLUSION: Although pituitary size was increased in a number of PROP1-deficient patients, none of them suffered permanent damage from pituitary mass; therefore, any proposed surgery should be postponed as long as possible and ultimately may not be necessary due to the self-limiting nature of the pituitary enlargement.

[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.

[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.

[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.

Pituitary enlargement in patients with PROP1 gene inactivating mutation represents cystic hyperplasia of the intermediate pituitary lobe. Histopathology and over 10 years follow-up of two patients.

Patients with a PROP1 inactivating mutation present combined pituitary hormone deficiency (CPHD) and pituitary maldevelopment. A retrospective analysis of 31 CPHD patients with a PROP1 mutation revealed two individuals, aged 18 and 4.5 years, who had undergone subtotal surgery to remove pituitary tumors, 16.8 x 12 mm and 9 x 10 x 12 mm in size. Histological reassessment of tissue samples revealed epithelial cells, partially oxyphilic, forming gland-like microcystic structures, most of them filled with eosinophilic colloid. These structures were directly linked with fragments of the posterior lobe. Neither atypia nor any traces of proliferation activity (Ki-67 LI=0%) were noted. Immunohistochemistry showed the presence of all hormonal phenotypes of cells. These findings corresponded to the intermediate lobe of the pituitary gland. For this type of pathology we propose the term 'cystic hyperplasia of the intermediate pituitary lobe' and suggest PROP1 gene assessment in patients with CPHD in order to avoid unnecessary neurosurgical interventions.