Autoimmune polyglandular endocrinopathy and anterior hypophysitis in a 14 year-old girl presenting with delayed puberty.

We report a 14 year-old peripubertal girl who presented at our clinic with the primary complaint of delayed puberty. She was asymptomatic except for vague complaints of fatigue. Physical examination was significant for mucosal hyperpigmentation and lack of secondary sexual characteristics. Laboratory evaluation revealed a morning cortisol concentration of <0.1 microg/dl (normal range [n.r.]: 4.3-22.4 microg/dl) and a simultaneous ACTH concentration of 2 pg/ml (n.r. 25-62 pg/ml); FSH 66.8 IU/l (n.r. for age: 1-12.8 IU/l); LH 41.1 IU/l (n.r. for age: 1-12 IU/l); E2 38 pg/ml (n.r. for age: 7-60 pg/ml). She had a flat cortisol response to an ACTH stimulation test. MRI of the pituitary gland failed to reveal a lesion. Plasma renin activity, thyroid function tests, parathyroid hormone, prolactin, IGF-I, IGFBP-3 concentrations and serum electrolytes were normal. However, her urinary sodium concentration was high. She was diagnosed with autoimmune polyglandular endocrinopathy including ovarian failure, adrenal failure and autoimmune anterior hypophysitis presenting as isolated ACTH deficiency. We emphasize that autoimmune etiology should be considered in the differential diagnosis of delayed puberty and ovarian failure and that the presence of other endocrinopathies should be searched for even in asymptomatic patients.

Low serum carnitine concentrations in healthy children with iron deficiency anemia.

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.

Factors influencing remission phase in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus (DM) is characterized by selective and progressive autoimmune destruction of beta-cells of the pancreas in genetically susceptible individuals. This autoimmune process takes years before the patient eventually develops clinical DM. Over the course of the disease, some patients regain their ability to secrete endogenous insulin to some extent for a period of few months to years. This partial remission phase has drawn a lot of attention since it offers a window of opportunity to intervene in an attempt to restore pancreatic beta-cell function or to prevent development of the disease in the prediabetic population at risk. Several factors, including age, sex, pubertal status, metabolic findings at the time of presentation, HLA types, presence of diabetes-associated autoantibodies, have been recognized to affect the likelihood of partial or complete remission in children with type 1 DM. Several interventions in patients with new-onset type 1 DM have been tried, including oral nicotinamide and immunomodulatory and immunosuppressive treatments, in an attempt to preserve beta-cell function and to promote or prolong the remission phase, but no conclusive data have been obtained so far. This review summarizes current knowledge on the factors that possibly influence the remission phase in children with type 1 DM.

In pubertal girls, naloxone fails to reverse the suppression of luteinizing hormone secretion by estradiol.

Estradiol (E2) negative feedback on LH secretion was examined in 10 pubertal girls, testing the hypothesis that E2 suppresses LH pulse frequency and amplitude through opioid pathways. At 1000 h, a 32-h saline infusion was given, followed 1 week later by an E2 infusion at 13.8 nmol/m2 x h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h, and four naloxone iv boluses (0.1 mg/kg each) were given hourly beginning at 1200 h on the following day. Blood was obtained every 15 min for LH determination and every 60 min for E2 determination from 1200 h to the end of the infusion. E2 infusion increased the mean serum E2 concentration from 44+/-17 to 112+/-26 pmol/L (P < 0.01). The mean LH concentration between 2200-1200 h decreased from 3.19+/-0.89 to 1.99+/-0.65 IU/L (P = 0.014), and LH pulse amplitude decreased from 3.4+/-0.6 to 2.6+/-0.5 IU/L (P = 0.0076). Although there were 1.2 fewer pulses during E2 infusion compared to saline infusion, differences did not reach significance (P = 0.1; 95% confidence interval for the difference, -3.5, 1.1). Pituitary responsiveness to GnRH, assessed at the end of the infusion by administering 250 ng/kg GnRH iv, did not change during E2 infusion. The effect of naloxone blockade of opioid activity on LH secretion was determined by assessing the area under the curve (AUC) from 1200-1600 h. During saline infusion, the LH AUC was 1122+/-375 IU/L during saline boluses and 1575+/-403 IU/L during naloxone boluses (P = 0.39). When E2 was infused, the LH AUCs during saline and naloxone boluses were 865+/-249 and 866+/-250 IU/L, respectively. Thus, in pubertal girls: 1) E2 decreases the LH concentration and LH pulse amplitude; 2) the main site of negative feedback effect of E2 appears to be at the level of the hypothalamus; 3) an increase in LH secretion after naloxone administration could not be demonstrated in these girls and may depend on the maturity of the hypothalamic-pituitary-gonadal axis; and 4) opioid receptor blockade does not reverse the E2 inhibition of LH secretion even in the most mature girls. Thus, E2 suppression of LH secretion in pubertal girls appears to be mediated by a decrease in hypothalamic GnRH secretion that is independent of opioid pathways.

Lymphocytic hypophysitis presenting with diabetes insipidus in a 14-year-old girl: case report and review of the literature.

UNLABELLED: Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. It is characterized by destruction and lymphocytic infiltration of the pituitary gland, probably by an autoimmune process, leading to a pituitary mass lesion and/or various degrees of hypopituitarism. The lesion is usually confined to the adenohypophysis. Posterior pituitary gland or stalk involvement is rare, although patients presenting with diabetes insipidus have been reported. We describe a girl aged 13 years 9 months with lymphocytic hypophysitis who presented with diabetes insipidus and secondary amenorrhea. MRI of the brain revealed a 1 cm enhancing mass in the pituitary stalk. A biopsy of the mass by right pterional craniotomy showed lymphocytic infiltration without neoplastic cells or granuloma formation. To our knowledge, this is the youngest reported patient with a diagnosis of lymphocytic hypophysitis. In this case report, her clinical presentation is discussed along with a review of the literature. CONCLUSION: We present the first childhood case of lymphocytic hypophysitis which is an autoimmune inflammatory disorder of the pituitary gland. Although this is a rare condition in adults, it also needs to be considered in the pediatric population. Conservative management is preferred unless there are signs of increased intracranial pressure. Most importantly, close monitoring for multiple hormone deficiencies is indicated in this condition.

Changes in serum immunoreactive and bioactive growth hormone concentrations in boys with advancing puberty and in response to a 20-hour estradiol infusion.

Acceleration of linear growth during puberty is associated with increased GH secretion, although the relationship between growth and GH is complex. As GH exists as a family of isoforms, some of which may not be identified by immunoassay, there may be alterations in isoform secretion during pubertal maturation that result in increased growth. The changes in serum immunoreactive and bioactive GH concentrations across pubertal maturation were determined in 30 boys, aged 6.5-19.3 yr, with idiopathic short stature or constitutional delay of adolescence. Data were grouped as follows: 1) 6 prepubertal boys with bone age 7 yr or less; 2) 5 prepubertal boys with bone age of more than 7 yr, 3) 10 boys in early puberty; 4) 9 boys with mid- to late puberty. Blood was obtained every 20 min from 2000-0800 h. An equal aliquot of each serum sample was pooled for determination of GH by bio- and immunoassays. The mean serum immunoreactive GH concentration increased from 2.1 +/- 0.3, 1.8 +/- 0.3, and 2.9 +/- 0.5 micrograms/L in groups 1, 2, and 3, respectively, to a peak of 4.6 +/- 0.7 micrograms/L in group 4 (P < 0.05 vs. groups 1-3). The mean serum GH bioactivity was 48 +/- 13 micrograms/L in group 1 and declined to 39 +/- 8 and 31 +/- 3 micrograms/L in groups 2 and 3, increasing to a maximum of 64 +/- 15 micrograms/L in group 4 (P < 0.05 vs. group 3). The ratio of bioactive to immunoreactive GH suggests that the biopotencies of secreted isoforms do not increase during pubertal maturation. The role of E2 in increasing GH secretion was characterized in 8 additional early pubertal boys. Each boy received a saline infusion from 1000-0800 h, followed 1 week later by an infusion of E2 at 4.6 nmol/m2.h. Blood was obtained every 15 min from 2200-0800 h for GH and LH and every 60 min for E2 and testosterone. An equal aliquot of each overnight serum sample was pooled for insulin-like growth factor I (IGF-I) and GH by immuno- and bioassays. The mean serum LH concentration decreased from 5.0 +/- 0.9 to 2.3 +/- 0.6 IU/L (P < 0.01), and the E2 concentration increased from 22 +/- 4 to 81 +/- 26 pmol/L (P < 0.01) during saline and E2 infusions, respectively. Mean serum GH concentrations as measured by immunoassay were similar during both infusions (6.6 +/- 1.4 vs. 9.7 +/- 2.1 micrograms/L; saline vs. E2 infusion, respectively). In contrast, the mean serum GH concentration, as measured by bioassay, decreased from 48 +/- 10 micrograms/L during saline infusion to 16 +/- 3 micrograms/L during E2 infusion (P < 0.05). The mean serum IGF-I concentration also decreased significantly from 116 +/- 17 to 93 +/- 15 micrograms/L (saline vs. E2 infusion, respectively; P < 0.05). Thus, although mean overnight serum GH concentrations increase in late puberty, whether measured by immuno- or bioassay, an acute increase in E2 produces an acute decline in serum GH bioactivity and a lesser decline in the serum IGF-I concentration. These unexpected changes indicate that E2 may affect pubertal growth and GH secretion in a complex or biphasic manner depending on the context in which it is administered.

Comparison of the neuroendocrine control of pubertal maturation in girls and boys with spontaneous puberty and in hypogonadal girls.

Puberty in boys is characterized by a nocturnal increase in mean LH concentration and LH pulse frequency. To determine whether similar mechanisms exist in girls, nocturnal serum LH concentrations were determined in 16 girls with constitutional delay of adolescence or idiopathic short stature who had or have subsequently been shown to have spontaneous puberty. Mean LH and LH pulse frequency and amplitude were analyzed in 3-h blocks and compared to those in 20 pubertal boys. Girls had an increase in mean LH concentration from 3.6 +/- 0.7 IU/L at 2000-2250 h to 4.8 +/- 0.9 IU/L at 0200-0450 h. LH pulse frequency increased from 0.27 +/- 0.11 pulses/girl.h at 2000-2250 h to 0.54 +/- 0.10 pulses/girl.h at 0200-0450 h. The increase in LH pulse amplitude, from 2.0 +/- 0.8 IU/L at 2000-2250 h to 4.1 +/- 1.1 IU/L at 2300-0150 h, did not achieve statistical significance because many girls had no pulses from 2000-2250 h. With advancing age, the day/night differences in LH concentration and LH pulse frequency disappeared in girls, but were preserved in boys of same pubertal stage. The effect of lack of estrogen on LH pulse characteristics was inferred by analyzing the LH profiles of 15 girls with gonadal dysgenesis who were age-matched to girls with spontaneous puberty. The girls with gonadal dysgenesis had an increase in mean LH concentration after 0200 h, but LH pulse frequency was rapid in all time blocks; the nocturnal increase in LH concentration was secondary to a significant increase in LH pulse amplitude. Older girls with gonadal dysgenesis had a loss of nighttime augmentation of LH secretion similar to that seen in girls with spontaneous puberty. These data suggest that the apparent slower LH pulse frequency encountered in girls with spontaneous puberty during waking hours may be related to estrogen suppression of LH pulse amplitude, which masks the true daytime LH pulse frequency. With or without pubertal estrogen exposure, developmental progression of LH secretion occurs more rapidly in girls than in boys. Thus, intrinsic sex differences exist in the timing and tempo of endocrine control of pubertal maturation between boys and girls.

Salmonella typhi infections. A 10-year retrospective study.

Enteric fever is still a common health problem in many countries, especially in children. Thus a ten-year retrospective study was carried out to evaluate the clinical and laboratory properties of enteric fever and the incidence of antimicrobial resistance in children. Throughout the past 10 years, Salmonella was isolated in 105 patients by blood culturing, 27 of which were Salmonella typhi. Most of the patients were above the age of two. Besides the typical symptoms and signs of enteric fever, 29.2% of the patients had some neurologic findings. Besides, 68.5% had elevated liver enzymes while only 44.4% had hepatomegaly with or without splenomegaly. Anemia was present in 44%, leukopenia in 16% and leukocytosis in 11.1% of the cases. The emergence of antimicrobial resistance during the last five years against ampicillin, chloramphenicol and trimetoprim-sulfamethoxazole has created a challenge in treating these infections.

Prognostic factors in Salmonella typhimurium septicemia. A 10-year retrospective study.

In this study, 74 S.typhimurium septicemia cases were evaluated retrospectively from their records, and the age and sex distribution, presence of underlying disease, signs and symptoms, complete blood count, liver function tests and case fatality rate were documented and prognostic factors determined. It has been shown that S.typhimurium is the most common strain causing Salmonella septicemia, which is more fatal in the newborn period and in the presence of an associated disease, while hemoglobin and leukocyte counts do not play an important role in the prognosis. In Salmonella septicemia, congenital heart disease was the second-most common associated disease, which may be attributed to probable underlying immunodeficiency.

Haematologic consequences of viral infections including serum iron status.

Twenty-seven children with mumps or chickenpox were taken as a model to evaluate the haematological consequences of viral infections including serum iron status. Blood samples were obtained from all patients at presentation and on the 21st day of the disease. While haemoglobin, haematocrit, and mean corpuscular volume levels were similar in two measurements (P > 0.05), the mean leucocyte, absolute lymphocyte and thrombocyte counts, mean serum iron, serum iron binding capacity and transferrin saturation levels were lower at presentation than on the 21st day of the disease. The serum iron levels were below 30 micrograms/dl in 16 (59.2%) patients at presentation while only 4 (14.8%) had low values on 21st day. Twenty-four (88.9%) patients had an increment in the serum iron binding capacity levels and 2 (7.6%) reached values above the normal range on the 21st day. In 21 (77.8%) patients, the transferrin saturation levels were below the expected ranges at presentation but 26 (96.3%) showed an increment on the 21st day. However, the mean ferritin level was higher at presentation. Therefore, during the evaluation of patients for anaemia, the presence of a recent acute viral infection should be documented so as to avoid unnecessary iron medication.

Acute lymphoblastic leukemia following optic glioma treated by radiotherapy and surgery.

A 14-year-old girl was diagnosed as having acute lymphoblastic leukemia following 5000 cGy cranial radiotherapy for treatment of optic glioma. In the absence of underlying predisposing factors, development of acute leukemia was attributed to the oncogenic effect of radiation.