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Growth hormone deficiency (GHD) is an important cause of decreased bone mass in childhood and adolescence. The role of other pituitary hormone deficiencies on bone mass is still a query in children. Thirty-nine children (28 with isolated GHD [IGHD] and 11 with multiple pituitary hormone deficiency [MPHD]) were investigated to show the effects of IGHD vs MPHD on bone status. Bone turnover markers (calcium, phosphate, alkaline phosphatase [ALP] Bone ALP [BALP], osteocalcin [OSC], carboxyterminal propeptide of type-1 collagen [CPP-I], parathyroid hormone [PTH]) were measured before and every four months during growth hormone (GH) therapy; bone mineral density (BMD) of the lumbar spine was measured before and every six months during therapy. All bone turnover markers except calcium and PTH increased significantly during 1 year of GH therapy. There were no differences in the levels of bone turnover markers between children with IGHD and MPHD at baseline, and after 4, 8 and 12 months of therapy. Lumbar spine BMD SDS of all patients increased significantly during 1 year of therapy (p = 0.035 after 6 months and p <0.001 after 12 months compared with baseline). BMD SDS of both IGHD and MPHD groups were similar at baseline and after 6 and 12 months of therapy (p = 0.235, p = 0.295 and p = 0.384). Height SDS (HtSDS) at baseline was the most important predictor of baseline BMD SDS in children with GHD (t = 4.166, p <0.001). DeltaHtSDS was also positively related to deltaBMD SDS after 1 year of GH therapy. In conclusion, there was no difference in bone status of the patients with IGHD and MPHD at baseline. GH therapy yielded similar increases in bone mass in both groups. Increase in height contributed to increase in BMD during 1 year of GH therapy.

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., (Copyright 2001 S. Karger AG, Basel)

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.

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., (Copyright 2002 S. Karger AG, Basel)

In this study the presence of pituitary-hypothalamic abnormalities was searched by magnetic resonance (MR) imaging in 30 children (18 males and 12 females, aged 7.4 to 23 years) with isolated growth hormone deficiency (IGHD). Small anterior pituitary was demonstrated in 18 patients and ectopic posterior pituitary (EPP) in four of them. Pituitary stalk was found to be thin in two patients with anterior pituitary hypophasia and EPP and was visible only in post-gadolinium images. In one patient, a hypothalamic mass was found and the bright spot of the posterior pituitary was found without diabetes insipidus, possibly due to a variation in the intensity of the bright signal. Eight patients had normal pituitary imaging suggesting functional damage. In all five patients with familial growth hormone deficiency the anterior pituitary was hypoplastic. We conclude that a high percentage of patients with IGHD had anomalies of the hypothalamo-pituitary region, which could be demonstrated by MR imaging. Furthermore, the low frequency of perinatal abnormalities in these patients suggested developmental defect as the cause of the morphostructural abnormalities. The presence of the familial cases with the same defect pointed to the genetic origin in some instances.

From a total of 118 patients treated for growth hormone deficiency, 37 (23 boys, 14 girls) have reached their final height. Twenty-five patients had isolated growth hormone deficiency (IGHD) and 12 had multiple pituitary hormone deficiency (MPHD). Growth hormone deficiency was diagnosed and treated late in both boys and girls. The mean height standard deviation score (SDS) for chronological age (CA) increased significantly from -4.43 to -1.94 during the therapy. The target height was not achieved in boys or girls nor in MPHD and IGHD groups, although they have reached the third percentile of the normal Turkish population. The height and chronological age of the patients at the start of the treatment correlated significantly with final height in all patients. Therefore, early diagnosis and treatment is important to complete catch-up growth in growth hormone deficient patients. The height prognosis is improved with administration of a recombinant form of human growth hormone (GH) as daily subcutaneous injections with a dose of 0.1 IU/kg, when compared to the earlier studies with pituitary GH.

The GH receptor (GHR) is a member of the cytokine receptor superfamily; GH binding protein is the solubilized extracellular domain of the GHR. Abnormalities in the GHR produce an autosomal recessive form of GH resistance, the Laron syndrome, characterized by growth failure and the clinical appearance of severe GH deficiency despite elevated circulating GH levels. In 13 unrelated patients with undetectable levels of GH binding protein, we characterized nine novel mutations in the GHR gene. These molecular defects comprise three nonsense mutations (Q65X, W80X, and W157X), one frameshift (36delC), two splice defects (G-->A at 70 + 1, C-->T at 723), and three missense mutations (C38S, S40L, and W50R) located in the extracellular domain of the receptor, and thus would be expected to interfere with GH binding activity. These results further confirm the broad heterogeneity of mutations underlying this rare GH resistance syndrome.

Clinical spectrum and endocrine details of thirteen Turkish children (age 0.3-14.2 years; eight females and five males; ten prepubertal, three pubertal) with growth hormone insensitivity are presented. All patients display phenotypical features of severe growth hormone deficiency. The diagnosis based on height standard deviation score (SDS), basal growth hormone (GH), basal insulin-like growth factor I (IGF-I, IGF-I response in an IGF generation test and growth hormone binding protein (GHBP) measurements. The median height SDS was -7.4 (range -3.2 to -10), weight for height index was 100 (range 81-152) and bone age/height age ratio was 2 (range 1.6-3.3). Endocrine investigations showed a median basal GH concentration of 61.4 mU/l (range 23.5-120 mU/l). Basal IGF-I level was below 10 ng/ml in all patients except one. None of the patients showed a significant IGF-I response to injections of GH (0.1 U/kg body weight for 4 days). The median IGFBP-3 level was 0.23 mg/l (range 0.1-0.56 mg/l). The GHBP level was undetectable in all of 10 patients. The high number of patients in our center may be due to the high rate of consanguinity among the Turkish population and the referral facility of our center in the area. These patients may benefit from the new therapy with recombinant human IGF-I.

The hospital records of 477 patients under 18 years of age with insulin-dependent diabetes mellitus (IDDM) who were followed in the Endocrinology Unit of Hacettepe University Children's Hospital between the years 1969 and 1991 were analyzed for age, sex, residence at time of diagnosis, date of onset of symptoms, date of diagnosis, family history of IDDM, and consanguinity between parents. The distribution of age at diagnosis showed a small peak between 4 and 6 years of age and a main peak between 12 and 14 years. In girls, the main peak appeared between 10 and 12 years, and in boys between 12 and 14. A significant difference was not seen between sexes (239 males and 236 females). The frequency of diagnosis showed seasonal variations the lowest in autumn and the highest in winter. Consanguinity between parents was 23.9 percent, and 10.3 percent of the patients had IDDM in first degree relatives.