Diazoxide-Induced Neutropenia and Long-Term Follow-up in a Patient with Hyperinsulinemia-Hyperammonemia due to GLUD1 Mutation.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

Genetic IGF1R defects: new cases expand the spectrum of clinical features.

PURPOSE: We aimed to identify the phenotypic variability of IGF1R defects in a cohort of short children with normal GH secretion gathered through the last decade. PATIENTS AND METHODS: Fifty children (25 girls) with short stature and a basal/stimulated growth hormone (GH) over 10 ng/ml having either a low birth weight or microcephaly were enrolled. MLPA and then Sanger sequence analysis were performed to detect IGF1R defects. The auxological and metabolic evaluation were carried out in index cases and their first degree family members whenever available. RESULTS: A total of seven (14%) IGF1R defects were detected. Two IGF1R deletions and five heterozygous variants (one frameshift, four missense) were identified. Three (likely) pathogenic, one VUS and one likely benign were classified by using ACMG. All children with IGF1R defects had a height < - 2.5SDS, birth weight < - 1.4SDS, and head circumference < - 1.36SDS. IGF-1 ranged from - 2.44 to 2.13 SDS. One child with a 15q terminal deletion had a normal phenotype and intelligence, whereas low IQ is a finding in a case with missense variant. Two parents who carried IGF1R mutations had diabetes mellitus, hypertension and hyperlipidemia, one of whom also had hypergonadotropic hypogonadism. CONCLUSION: We found a deletion or variant in IGF1R in 14% of short children. Birth weight, head circumference, intelligence, dysmorphic features, IGF-1 levels and even height are not consistent among patients. Additionally, metabolic and gonadal complications may appear during adulthood, suggesting that patients should be followed into adulthood to monitor for these late complications.

Acquired resistance to pamidronate treated effectively with zoledronate in juvenile Paget's disease.

Juvenile Paget's disease (JPD) is a rare autosomal recessive osteopathy. There is still a question about the most effective treatment modality in long-term prognosis. A 9-month-old boy who suffered from bone pain and deformities with a very high alkaline phosphatase level was diagnosed as JPD by radiographic findings. Genetic analysis showed a homozygous large deletion in TNFRSF11B gene encoding osteoprotegerin. Clinical improvement was observed with intravenous pamidronate therapy. However, the effect of drug reduced in time so the annual dose per kilogram body weight was increased after 2 years. Despite this increment, bone fractures developed and bone pain recurred with high-ALP levels, which suggested resistance to pamidronate. Switching to zoledronate resulted a significant improvement in bone findings radiographically and ALP level. Severe hypocalcemia requiring intravenous calcium treatment complicated the first dose of zoledronate, but not recurred thereafter. Intravenous pamidronate therapy is effective in reducing bone pain, improving bone deformities and motor development in infantile onset JPD. However, this effect can be transient. Switching to another bisphosphonate like zoledronate may provide long-term clinical and biochemical improvement as an alternative treatment in case of resistance to pamidronate therapy.

Intrapartum, postpartum characteristics and early neonatal outcomes of idiopathic polyhydramnios.

This paper investigates the effect of idiopathic polyhydramnios on the intrapartum and postpartum characteristics of labour and early neonatal outcomes. In this study, intrapartum and early neonatal outcomes of 207 women with idiopathic polyhydramnios and 336 matched healthy pregnant patients were evaluated. In the case of idiopathic polyhydramnios, the active phase of labour became longer when compared to the control group (5.76 ± 3.56 h vs. 4.38 ± 2.8 h, p: 001). The risk of preterm birth (OR 5.23; 95% CI: 2.04-13.42) and caesarean section (OR 2.26; 95% CI: 1.56-3.28) was higher in women with IP. Patients with IP had a higher rate of transcient tachypnoea of the newborn (TTN), newborn resuscitation, admission to neonatal intensive care unit (NICU), ventilator requirement, newborn jaundice, newborn hypoglycaemia and structural anomalies. IP did not cause any appreciable maternal risk during the intrapartum or postpartum periods. However, neonatal morbidity and post-natal anomaly rates were higher in the case of IP.

Risk factors for clavicle fracture concurrent with brachial plexus injury.

PURPOSE: The aim of this study was to evaluate the risk factors for clavicle fracture concurrent with brachial plexus injuries. METHODS: A retrospective study was conducted at a tertiary centre. The hospital records of 62,288 vaginal deliveries were evaluated retrospectively. There were 35 cases of brachial plexus injury. Of these patients, nine had brachial plexus injuries with clavicle fracture and 26 without clavicle fracture. The analysed risk factors for clavicle fracture concurrent with brachial plexus injury were gestational diabetes, labour induction and augmentation, prolonged second stage of labour, estimated foetal weight above 4000 g, birth weight above 4000 g, risky working hours, and the requirement of manoeuvres to free the impacted shoulder from behind the symphysis pubis. RESULTS: Labour augmentation with oxytocin increased the risk of clavicle fracture in cases of brachial plexus injury (OR 6.67; 95% CI 1.26-35.03). A birth weight higher than 4000 g also increased the risk of clavicle fracture. Risky working hours, gestational diabetes, estimated foetal weight higher than 4000 g, and requirement of shoulder dystocia manoeuvres did not increase the risk of clavicle fracture. CONCLUSIONS: Labour augmentation and actual birth weight higher than 4000 g were identified as risk factors for clavicle fracture in cases of brachial plexus injury.

N-acetylcycsteine attenuates the deleterious effects of radiation therapy on inci-sional wound healing in rats.

BACKGROUND: During preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats. MATERIAL & METHODS: Forty Wistar albino rats were randomized into four groups containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy was performed to all groups (Groups 1-4). Group 1 was designed as a control group without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal NAC, respectively. RESULTS: Group comparisons demonstrated that breaking strength was significantly higher in NAC treated rats. A statistically significant difference was determined in terms of superoxide dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups (p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were found to be similar between groups (p=0.163). Serum GSH and SOD levels were significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05). Similarly, there was a significant increase in serum MDA concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p < 0.05). There was not a significant difference between Groups 3 and 4 regarding GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization. CONCLUSION: The present study supports the hypothesis that NAC administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration.

Efficacy and safety of pneumatic trabeculoplasty versus timolol added to latanoprost in primary open angle glaucoma.

BACKGROUND: To compare the safety and short-term additive hypotensive effect of pneumatic trabeculoplasty (PNT) versus timolol among patients receiving topical latanoprost for primary open angle glaucoma (POAG). PATIENTS AND METHODS: This study prospectively evaluated 30 eyes of 30 patients with POAG receiving latanoprost monotherapy. We randomly assigned 15 eyes to PNT plus latanoprost (Group A), and 15 eyes to latanoprost/timolol fixed combination therapy (Group B). PNT treatment was performed at days 0, 7, and 90. Follow-up visits occurred at day 1, week 1, and months 1 and 3. RESULTS: Compared to baseline values, both treatments significantly lowered IOP (p ≤ 0.001).The mean IOP for Group A was 21.13 ± 1.6 mmHg at baseline and 18.7 ± 1.5 mmHg at three months (p ≤ 0.001). For Group B, mean IOP was 20.8 ± 1.9 mmHg at baseline and 18.9 ± 0.8 mmHg at three months (p ≤ 0.001). Transient conjunctival hyperaemia, the only adverse effect occurring after PNT, was observed in all patients in Group A. CONCLUSION: The additive IOP-lowering effect of PNT was similar to timolol in patients with POAG receiving latanoprost.

Variations in tumor marker levels in metastatic breast cancer patients according to tumor subtypes.

PURPOSE: To investigate whether serum CA 15-3 and CEA levels show differences among subgroups of breast cancer patients at the time of diagnosis of early-stage disease and at disease relapse. METHODS: Patients with metastatic breast cancer diagnosed from 2000 to 2010 were retrospectively analyzed. Data were obtained from medical charts. CA 15-3 and CEA levels of patients with metastatic disease at the time of diagnosis or who relapsed during follow-up were evaluated. Four different breast cancer subtypes were defined: estrogen receptor (ER) and/or progesterone receptor (PR) positive and HER-2 negative (luminal A), ER and/or PR positive and HER-2 positive (luminal B), ER and PR negative and HER-2 positive (HER-2 overexpressing) and triple negative (ER, PR and HER-2 negative). Fifty-eight (13.7%) of the patients were metastatic at the time of diagnosis. RESULTS: 423 metastatic breast cancer patients were included. Of the patients, 232 (54.8%) had luminal A disease, 70 (16.5%) luminal B, 53 (12.5%) HER-2 overexpressing, and 68 (16.1%) triple negative disease. Preoperative CA 15-3 levels were raised in 48.1% of the luminal A group, in 42.8% of the luminal B group, in 26.0% of the HER-2 overexpressing group, and in 33.3% of the triple negative group. CA 15-3 levels after relapse were raised in 44.5% of the luminal A group, in 33.3% of the luminal B, in 28.9% of the HER-2 overexpressing, and in 38.8% of the triple negative group. Preoperative CEA levels were elevated in 44.3% of the luminal A group, in 28.5% of the luminal B, in 43.4% of the HER-2 overexpressing, and in 14.3% of the triple negative group. CEA levels after relapse were raised in 60.8%, 54.7%, 51.1%, and 36.0% of the patients in the 4 subgroups, respectively. CONCLUSION: This study showed that there are differences between the breast cancer subgroups in terms of tumor marker levels in metastatic breast cancer patients. Tumor marker elevation was lower in the triple negative group as compared to the luminal groups. Monitoring CEA levels in luminal A group may be beneficial in determining early relapses. However, this retrospective study requires further prospective confirmative cohort studies.

Anemia and neutropenic fever with high dose diazoxide treatment in a case with hyperinsulinism due to Munchausen by proxy.

BACKGROUND: The etiology of hyperinsulinemic hypoglycemia in adolescents is similar to that of adults. Patients resistant to medical treatment may undergo pancreatectomy. Diazoxide is the mainstay of medical treatment. Rarely bone marrow suppression is reported due to diazoxide. PATIENT: An adolescent with severe hyperinsulinemic hypoglycemia was referred for pancreatectomy after she was treated with high doses of diazoxide, octreotide and glucose. She developed anemia and febrile neutropenia in the course of diazoxide treatment that resolved with cessation of medication. The cause of the hyperinsulinemia proved to be classical Munchausen by proxy. CONCLUSION: This is the first report of bone marrow suppression involving erythroid series by diazoxide. Follow-up of blood count may be considered in patients on high dosages since anemia may be dose dependent. Munchausen by proxy poses a serious threat to children with significant morbidity and mortality. Awareness and a high index of suspicion in clinical settings with unusual causes are the mainstay for the diagnosis.

c-Kit (CD117) expression in classic Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is a multicentric, low-grade, vascular neoplasia. Human herpesvirus 8 is associated with all epidemiological forms of KS and has been shown in vitro to induce the tyrosine receptor kinase c-Kit in infected cells. AIM: To investigate the expression of c-Kit in cases of classic KS and to clarify its association with clinicopathological parameters and HHV8 latency-associated nuclear antigen-1 expression. METHODS: In total, 35 cases of classic KS at various histological stages were included in the study. Age and gender of the patients and location and histological stage of the tumours were recorded. Formalin-fixed, paraffin wax-embedded tissue sections were stained by immunohistochemistry with antibodies to c-Kit and HHV8. RESULTS: c-Kit immunoreactivity was found in 22 cases and HHV8 immunoreactivity was present in all cases. There was no correlation in c-Kit immunoreactivity between clinicopathological parameters and HHV8 immunoreactivity. CONCLUSIONS: The results of our study show that in cases of classic KS there is a high rate of c-Kit immunoreactivity, but c-Kit expression does not show any correlation with HHV8 immunoreactivity.

Assessment of thyroid function during the long course of Hashimoto's thyroiditis in children and adolescents.

CONTEXT: The prognosis of Hashimoto's thyroiditis (HT) in children and adolescents is not well known and studies reporting long-term outcome of the disease are scarce. OBJECTIVE: To assess the thyroid hormone status during long-term follow-up and to establish the prognosis of children and adolescents with HT. PATIENTS: One hundred and twenty-nine patients with HT were re-evaluated for thyroid hormone status after a mean follow-up period of 50 months. RESULTS: Seventy-seven per cent of the euthyroid patients were still euthyroid, while 21.1% of these patients became hypothyroid at the time of re-evaluation. However, 69.5% of hypothyroid patients remained hypothyroid (overt or subclinical) and 30.5% recovered. CONCLUSION: HT is a dynamic process. Thyroid functions can show variation during follow-up. Therefore, thyroid function tests should be repeated periodically to detect progression to hypothyroidism in initially euthyroid patients as well as reversibility of hypothyroidism.

Hashimoto's thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease.

UNLABELLED: Hashimoto's thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents in iodine replete areas. To find out the clinical, epidemiological and laboratory characteristics of the disease in childhood, we reviewed files of 162 children and adolescents with HT followed in the Department of Pediatric Endocrinology, Hacettepe University Faculty of Medicine. RESULTS: Female patients constituted 86.4% (n = 140) of all patients with a female:male ratio of 6.4. Mean age at diagnosis was 11.4 +/- 2.97 years (age range 4.4-16.5 years). At the time of diagnosis 43.2% of the patients (n = 70) were euthyroid, 24.1% (n = 39) had subclinical hypothyroidism, 21% (n = 34) had overt hypothyroidism, and 8.6% (n = 14) had overt and 3.1% (n = 5) subclinical hyperthyroidism. CONCLUSIONS: Autoimmune thyroiditis is more frequent in females, and increases in frequency over age during childhood and adolescence. At the time of diagnosis, frequency of overt and subclinical hypothyroidism is similar to that of euthyroid goiter.

Marker assisted genetic analysis of non-brittle rachis trait in barley.

Brittle rachis is a head shattering mechanism of barley. Two tightly linked complementary genes, btr1 and btr2, were believed to control the non-brittle rachis trait. Position of non-brittle rachis loci btr1btr2 on the short arm of Chromosome 3 was investigated using RFLP markers. Two approaches were employed. First, a Hordeum vulgare subsp. spontaneum fragment that confers brittleness in a cv. Bowman near isogenic line was detected. This fragment is 18-33 cM in length and contains MWG798B, ABG057, MWG014, BCD706 and KFP216 markers of the short arm of Chromosome 3. In the second approach, position of btr1 locus in a H. vulgare subsp. spontaneum (Wadi Qilt 23-38)xH. vulgare subsp. vulgare (cv. Harrington) cross was detected using a selective genotyping approach in BC2F1 generation. F-tests and analysis of genotypic compositions of BC2F1 lines showed that btr1 locus, and supposedly the tightly linked btr2 locus, is in 4.3 cM KFP216-RisP114 interval of short arm of Chromosome 3. Results also yielded clues for the presence of at least two additional loci that affect the non-brittle rachis trait. Allelism tests using genotypes with known non-brittle rachis gene compositions provided additional evidence for presence of such loci.

A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis.

The rare bone thickening disease osteopetrosis occurs in various forms, one of which is accompanied by renal tubular acidosis (RTA), and is known as Guibaud-Vainsel syndrome or marble brain disease. Clinical manifestations of this autosomal recessive syndrome comprise increased bone density, growth failure, intracerebral calcification, facial dysmorphism, mental retardation, and conductive hearing impairment. The most common cause is carbonic anhydrase II (CAII) deficiency. Several different loss of function mutations in CA2, the gene encoding CAII, have been described. To date, there have been no exceptions to the finding of CAII deficiency in patients with coexistent osteopetrosis and RTA. Most often, the RTA is of mixed proximal and distal type, but kindreds are reported in which either distal or proximal RTA predominates. We report the molecular genetic investigation of two consanguineous kindreds where osteopetrosis and distal RTA (dRTA) were both manifest. One kindred harbours a novel homozygous frameshift alteration in CA2. In the other, CAII levels were normal despite a similar clinical picture, and we excluded defects in CA2. In this kindred, two separate recessive disorders are penetrant, each affecting a different, tissue specific subunit of the vacuolar proton pump (H(+)-ATPase), providing a highly unusual, novel genetic explanation for the coexistence of osteopetrosis and dRTA. The osteopetrosis is the result of a homozygous deletion in TCIRG1, which encodes an osteoclast specific isoform of subunit a of the H(+)-ATPase, while the dRTA is associated with a homozygous mutation in ATP6V1B1, encoding the kidney specific B1 subunit of H(+)-ATPase. This kindred is exceptional firstly because the coinheritance of two rare recessive disorders has created a phenocopy of CAII deficiency, and secondly because these disorders affect two different subunits of the H(+)-ATPase that have opposite effects on bone density, but which have only recently been determined to possess tissue specific isoforms.

Fludrocortisone treatment in a child with severe cerebral salt wasting.

Hyponatremia is a common complication of intracranial disease or surgery. An evaluation should be undertaken to determine whether cerebral salt wasting (CSW) or inappropriate secretion of antidiuretic hormone is present as a cause. Since the treatment principles are completely different in the two pathological states, differential diagnosis is very important. CSW is defined as the renal loss of sodium leading to hyponatremia and decreased extracellular fluid volume. In the literature, it has been noted that mineralocorticoid administration can be useful in CSW cases. We herein present an 11-year-old boy who developed hyponatremic seizures after intracranial tumor resection. He was diagnosed with CSW on the basis of high urinary sodium excretion and increased urine output, together with signs and symptoms of dehydration. Despite intensive fluid and salt therapy, we were unable to decrease the urinary output. Therefore, fludrocortisone therapy was administered and his urinary output and sodium excretion were decreased and his serum sodium level was normalized. In conclusion, in addition to fluid and salt replacement, mineralocorticoid supplementation also seems to be a safe and effective treatment for CSW.

True hermaphroditism: clinical features, genetic variants and gonadal histology.

True hermaphroditism is a rare cause of intersexuality in which both ovarian and testicular tissue is present in the same individual. We present the clinical findings, karyotype, gonadal histology and management of eight patients with true hermaphroditism. Their ages ranged from 43 days to 12 years at the first evaluation. The presenting symptoms were ambiguous genitalia (6 patients), isolated clitoromegaly (1 patient) and hypospadias (1 patient). The most common karyotype was 46,XX (6 patients). In one patient the karyotype was 46,XY and in another 45,XO/46,XY mosaicism, which is rare in the literature. A vagina was found by genitography in all patients, and at laparotomy the uterus was found normal in five patients, hypoplastic in one patient, as a fibrous band in one, and absent in the remaining patient. Histological investigation of the gonads revealed bilateral ovotestis in two patients, ovotestis plus ovary in two patients, and ovary on one side and testis on the other side in three patients. Five patients were assigned to the female sex, and three to the male sex. One of these patients was changed from male to female after evaluation.

Comparison of stimulated growth hormone levels in primed versus unprimed provocative tests. Effect of various testosterone doses on growth hormone levels.

OBJECTIVE: To show the importance of priming prior to growth hormone (GH) stimulation tests in the diagnosis of GH deficiency, the effect of different doses and schedules of testosterone (T) on GH levels. PATIENTS AND METHODS: Eighty-four prepubertal and early pubertal boys whose heights were 2 SD below the mean and height velocities <4 cm per year and who failed in GH stimulation tests were included in the study. The boys were divided into two groups: the first group consisting of 41 boys was primed with 62.5 mg/m(2) (low dose testosterone - LDT) and the second group consisting of 43 boys with 125 mg/m(2) depot testosterone (conventional dose testosterone - CDT) intramuscularly 1 week before the stimulation test. Twenty-one boys out of 36 who failed in GH stimulation tests after one dose T injection were treated with three doses of 62.5 mg/m(2) T (multiple dose testosterone - MDT) injections monthly and retested. RESULTS: The GH levels increased from 4.80 +/- 2.78 to 11.50 +/- 8.84 ng/ml and from 4.76 +/- 2.46 to 12.98 +/- 8.30 ng/ml by priming with LDT and CDT respectively. The increment of mean GH levels by both LDT and CDT were found to be similar (p = 0.443). The peak GH levels were found to be elevated >10 ng/ml in 22/41 (54%) and 26/43 (60%) who received LDT and CDT respectively (p = 0.528). The mean GH level of 21 boys who received MDT was increased from 5.38 +/- 2.50 ng/ml (by priming with one dose T) to 10.19 +/- 6.13 ng/ml (p = 0.004). Twelve (57%) of 21 boys who received MDT responded to GH stimulation test >10 ng/ml. The T level increased from 0.71 +/- 0.97 to 4.54 +/- 2.80 ng/ml by LDT (p < 0.001) and from 0.65 +/- 0.71 to 7.18 +/- 3.18 ng/ml by CDT (p < 0.001). The increment of T level was higher by CDT than LDT (p = 0.001). There was no correlation between T and peak GH levels after priming. CONCLUSION: LDT is as effective as CDT in priming of GH stimulation tests. The ones who failed in GH stimulation tests after one dose T injection can be primed with MDT. The stimulated GH level after priming was related neither to the plasma level of T nor the dose of T.

Height prognosis in children with late-diagnosed congenital hypothyroidism.

It is a general belief that early and adequate thyroid hormone replacement achieves normalization of growth as well as disappearance of clinical sings and symptoms of hypothyroidism. Due to the lack of comprehensive growth studies, height prognosis has remained controversial in late-diagnosed hypothyroidic children. The limited number of previous studies have suggested permanent height deficit in these children. In this study we present longitudinal growth and final height of 20 children (14 females and 6 males) in whom the duration of hypothyroidism before onset of therapy varied from three to 12.6 years. The etiological distribution of cases revealed ectopic thyroid tissue in nine cases, agenesis in seven, and dyshormonogenesis in four cases. At the time of the diagnosis all hypothyroidic children had severe growth retardation (mean height SDS +/- SD -3.95+/-1.07) due to prolonged hypothyroidism. Although the catch-up spurt corrected an important part of the initial height deficit in all patients, only nine patients reached or exceeded their target height, and the final height of five patients remained below 2 SD of mean. Despite treatment, prolonged hypothyroidism may result in compromised adult height in some patients. The contributing factors to this height deficit may include the duration of hypothyroidism, the height deficit at the time of the diagnosis, etiological differences and the diminished potential for catch-up growth in late-diagnosed hypothyroidism.

Pituitary adenoma associated with gigantism and hyperprolactinemia.

An 11-year-old girl presented with excessive growth, headache, left visual loss and seizures. Her growth hormone (GH) and prolactin (PRL) levels were high and magnetic resonance imaging findings showed an invasive macroadenoma. Gross total tumor removal was performed and then radiotherapy and medical therapy were given. During the follow-up, she developed ACTH deficiency, secondary hypothyroidism and hypogonadism requiring replacement therapy. It is still unclear whether the biological characteristics of GH- and PRL-secreting tumors are different in children from those in adults. More data are needed before a definitive conclusion can be established.

Magnetic resonance imaging in growth hormone deficiency: relationship between endocrine function and morphological findings.

Magnetic resonance imaging (MRI) using gadopentetate dimeglumine (Gd-DTPA) improves the delineation of hypothalamic-pituitary structures and facilitates the detection of anatomical abnormalities which are indicators of permanent growth hormone deficiency (GHD). The aim of this study was to determine the frequency of neuroradiological abnormalities in 85 (52 M, 33 F) patients with hereditary or idiopathic forms of isolated GHD (IGHD) or multiple pituitary hormone deficiency (MPHD) and also to investigate the relationship between anatomical findings and hormonal status. Pituitary hypoplasia with absent or thin infundibulum and ectopic posterior pituitary (EPP) were the most frequent findings in 39 patients with MPHD, whereas in 46 patients with IGHD the most frequent finding was pituitary hypoplasia without neuroradiological abnormalities. All patients whose infundibulum was not visualized after Gd-DTPA injection belonged to the MPHD group; therefore, absence of pituitary stalk can be a good indicator of the severity of hormonal deficiencies. Pituitary hypoplasia was found in all patients with familial IGHD. Among patients with abnormalities of the hypothalamic pituitary area on MRI, normal or breech delivery frequency distributed equally. Therefore it seems that mechanical or hypoxic prenatal events cannot be the primary etiological factor in all patients with neuroradiological abnormalities since half of these patients had normal delivery and birth history. The localization of the bright spot of the posterior pituitary at the level of the median eminence, midstalk position or at the end of the infundibulum may suggest a neuronal migration defect which may occur during early embryogenesis. In conclusion, in children with GHD a careful examination of the hypothalamic pituitary area by MRI after enhancement helps to establish the diagnosis and predicts the prognosis.