The effect of a dietary portfolio compared to a DASH-type diet on blood pressure.

BACKGROUND AND AIM: Compared to a DASH-type diet, an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the relation to sodium (Na(+)), potassium (K(+)), and portfolio components. METHODS AND RESULTS: 241 participants with hyperlipidemia, from four academic centers across Canada were randomized and completed either a DASH-type diet (control n = 82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n = 159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with 24-h urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg (95% CI, 4.2 to -0.1 mm Hg) (p = 0.056), 1.8 mm Hg (CI, 3.2 to 0.4 mm Hg) (p = 0.013) and 1.9 mm Hg (CI, 3.4 to 0.4 mm Hg) (p = 0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (ρ = -0.15 to -0.17, p ≤ 0.016) as did urinary potassium (ρ = -0.25, p = 0.001), while the Na(+)/K(+) ratio was positively associated (ρ = 0.20, p = 0.010). CONCLUSIONS: Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet. CLINICAL TRIAL REG. NO.: NCT00438425, clinicaltrials.gov.

Dexamethasone in the diagnostic work-up of growth hormone deficiency.

OBJECTIVE: Acute administration of dexamethasone (dexa) has recently been shown to induce growth hormone (GH) release. To ascertain the efficacy of this stimulus in assessing GH secretory status in children, we tested it in a large group of patients with short stature. METHODS: We administered dexamethasone at the dose of 2 mg/m2 to 44 short normal children and 19 GH deficient (GHD) children, either orally or intravenously and compared the results of the dexa-test to the more classical clonidine test. RESULTS: The oral dexa-test induced a GH peak similar to the clonidine test (clo) (controls clo: 23.8 +/- 7.8 mU/l, median 22.8, range 15.2-45.4 vs. control dexa: 20.6 +/- 10.8, median 16.8, range 8-47, P = 0.2. GHD clo: 9.8 +/- 2.6, median 9.2, range 6.4-13.4 vs. GHD dexa: 9.4 +/- 3.4, median 10.2, range 4.6-14, P = 0.8). Its sensitivity and specificity with respect to the clonidine test were 91% (10/11 GHD) and 65% (15/23 controls), respectively. The GH peak after i.v. dexa was smaller than that after clonidine (control clo: 30.6 +/- 14 micrograms/l, median 24.8, range 14.2-62.4 vs. control dexa: 21.6 +/- 5.4, median 21.6, range 11.2-33, P = 0.01. GHD clo: 7.4 +/- 4.2, median 8.8, range 0.4-11.8 vs. GHD dexa: 6.4 +/- 5.6, median 5.8, range 0.4-16.2, P = 0.17) with sensitivity and specificity of 87% (7/8 GHD) and 90% (19/21 controls), respectively. The lower potency of dexamethasone could account for these figures, since when a different cut-off was used (12 mU/l and 11 mU/l for the oral and i.v. route) both sensitivity and specificity were improved. More data are needed to support these findings and establish a clear cut-off. In the control group, no difference was found between GH peak after oral or i.v. dexa but GH-area under the curve (AUC) was larger for i.v. than for oral dexa. No side effects were noted. CONCLUSIONS: Intravenous dexamethasone appears to be a promising stimulus for the detection of GH deficiency in children, particularly for use in outpatients.

Evidence of a congenital midline brain anomaly in pituitary dwarfs: a magnetic resonance imaging study in 101 patients.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain in pituitary dwarfs has revealed a previously unknown entity: ectopia of the posterior pituitary (PPE), absence or hypoplasia of the pituitary stalk and hypoplasia of the anterior pituitary. The pathogenesis of these findings was explained originally by a traumatic transection of the pituitary stalk during delivery. A high incidence of breech delivery has been reported in these groups, but the traumatic hypothesis cannot explain the findings in the relatively high percentage of patients with normal delivery, nor account for a different feature also found in other pituitary dwarfs consisting of pituitary hypoplasia with normal posterior pituitary. A second hypothesis could then been proposed, based on dysgenesis or abnormal embryonic development of both adenohypophysis and neurohypophysis. OBJECTIVE: To review the value and significance of these two different etiopathogenetic hypotheses by analyzing clinical, endocrinological, and MRI findings in a large population of pituitary dwarfs. METHODS: One hundred and one consecutive patients with congenital idiopathic growth hormone deficiency (CIGHD) were studied by MRI; they were compared with a control group of 46 healthy short children. A complete clinico-endocrinological evaluation was obtained in both patients and controls to assess the perinatal history, the pituitary-hypothalamic function, and the neurological status. MRI studies were evaluated both qualitatively and quantitatively and the pituitary volume (PV) was calculated in both patients and controls. Quantitative data were statistically analyzed to compare the mean PV of the patients with the mean PV of controls, the hormonal therapy, the single or multiple pituitary hormone deficiency, and the presence of breech delivery. RESULTS: MRI revealed PPE in 59 patients and a normal posterior pituitary (NPP) in 42. PV was extremely small in patients with PPE and in patients with NPP associated with a severely narrowed pituitary stalk; mean PV was significantly lower in CIGHD patients when compared with that of healthy short children. PV was not influenced by hormonal therapy and did not differ between patients with single and multiple pituitary hormone deficiency and between patients with normal and breech delivery. PPE patients differed from NPP patients for a higher male/female ratio (3:1 vs 1:1) and for a greater frequency of multiple pituitary hormone deficiency (49% vs 12%), breech delivery (32% vs 7%), and associated congenital brain anomalies (12% vs 7%). In PPE patients breech delivery was strongly associated with multiple pituitary hormone deficiency. CONCLUSION: On the basis of this study the traumatic hypothesis could theoretically explain the pathogenesis of PPE only in 32% of the patients with this condition. On the basis of modern understanding of embryogenesis of anterior and posterior pituitary, it is then justified to propose that a defective induction of mediobasal structure of the brain in the early embryo could account for both the complex morphological MRI abnormality and the clinico-endocrinological features encountered in all PPE patients. The close contiguity between the future pituitary and hypothalamus, the peculiar association with congenital midline brain anomalies, and the recent data about a possible role of Pit-1 gene, all support the hypothesis of a congenital defect. Finally, breech delivery can be considered not as a cause of PPE, but as an effect of the embryonic pituitary-hypothalamic abnormalities.

Persisting functional connection in growth-hormone-deficient patients with a transected stalk.

Prolactin response after domperidone (DOM) stimulus was used to investigate the functional status of the hypothalamo-hypophyseal axis in 57 congenital growth-hormone-deficient (GHD) children with and without magnetic resonance imaging (MRI) abnormalities. Response to DOM was significantly lower in the GHD children compared with controls, using maximum peak (p < 0.0001), increase (p < 0.0001) or percentage increase (p < 0.05). The lowest values were observed in patients with hypophyseal stalk transection. Thus, the DOM test revealed reduced dopaminergic transmission in GHD subjects, more severe in the transected group, in whom, however, a response to the stimulus was still present. Therefore, it seems that a residual hypothalamo-hypophyseal connection is preserved even if it is not detectable with MRI.

Growth hormone deficiency in children: role of magnetic resonance imaging in assessing aetiopathogenesis and prognosis in idiopathic hypopituitarism.

To search for the presence of morphostructural abnormalities of the hypothalamus-pituitary region in growth hormone deficient (GHD) children magnetic resonance imaging (MRI) was performed in 30 GHD patients (age 10.09 +/- 3.5 years) and in 15 healthy age-matched controls. MRI demonstrated a significantly small sella and pituitary volume compared to controls and normal literatures values. In 20 patients the structures were extremely small and an abnormal development of the pituitary stalk was observed, and in 18 of these patients the bright spot indicating the neurohypophysis was dislocated to the distal part of the maldeveloped stalk, although these children had a normal fluid balance. From a functional point of view hypothalamus and pituitary defects were equally distributed between the two morphological groups. The patients with multiple endocrine defects had the smallest pituitary volume and abnormal stalk. A possible pathogenetic role of perinatal trauma or dysembryogenic events are discussed. A careful follow up of patients with isolated GHD presenting MRI abnormalities of the pituitary is suggested for the possible evolution in panhypopituitarism.

Long term growth hormone (GH)-releasing hormone and biosynthetic GH therapy in GH-deficient children: comparison of therapeutic effectiveness.

Twenty-five GH-deficient children were treated with GHRH (1-44), once daily sc for 6-24 months. At the 6th month of therapy, 40% of our patients showed a catch-up growth (responders), while the remaining 60% did not (nonresponders). No differences in auxological and biological variables at inclusion were found between the two groups. However, integrated GH secretion elicited by iv GHRH at inclusion was significantly (p less than 0.025) higher in responders than in non responders. During GHRH therapy, no significant increase in IGF 1/SmC was found in both groups. In all patients treatment was discontinued after 6-24 months, when its effect on growth rate failed. After a wash-out period of at least 6 months, patients were submitted to biosynthetic GH therapy. After 6 months of GH treatment a significant catch-up growth was found in both responder and non-responder children. Although the majority of GH-deficient children have hypothalamic rather than pituitary dysfunction, GHRH therapy is found to be less effective than GH treatment. Other methods of GHRH administration are worth investigating.

Evidence of morphological and functional abnormalities in the hypothalamus of growth-hormone-deficient children: a combined magnetic resonance imaging and endocrine study.

Fifty-seven children with growth hormone deficiency and 15 healthy age-matched controls were studied by magnetic resonance imaging (MRI). Of the patients, 36 (63%) had isolated GH deficiency (IGHD) and 21 (37%) multiple pituitary hormone deficiency (MPHD). MRI studies showed a marked reduction in pituitary volume in all patients in comparison with normal controls. Moreover, a striking morphological abnormality with the apparent absence of the pituitary stalk and an ectopic posterior pituitary lobe was detected in 34 of the patients (59%). This pituitary stalk abnormality was detected in 95% of the MPHD patients and in 39% of the IGHD patients. All but one of the patients with a normal pituitary stalk had IGHD. Endocrine evaluation showed no correlation with MRI data: in particular patients with an apparent anatomical interruption of the hypothalamic-pituitary axis showed a variety of patterns of hormonal responses. In conclusion, our study shows a high frequency of hypothalamic-pituitary anomalies in patients with GH deficiency, particularly related with MPHD. However, further studies are needed to improve our understanding of the relationship between MRI and endocrine data.

[New perspectives on the treatment of growth hormone deficiency]. / Recenti prospettive nella terapia del deficit di GH.

In the last few years the therapeutic management of GHD children has been improved by the recent synthesis of GH by DNA recombinant technique (rGH). rGH made it possible to overcome the problems of availability and purity of extractive GH, obtaining the same results (in growth velocity) without any information as regards late side effects of such a treatment. GHRH therapy in GHD patients of hypothalamic origin is still on trial and a lot of aspects are to be pointed out (indications to treatment, schedule and route of administration, cost/benefit ration, side effects).

Tolerance of the oral clonidine test in 75 pediatric patients.

We evaluated the tolerance and effectiveness of the oral clonidine test for GH in 75 children, 84% with hyposomia and 16% with other diseases. The test was well tolerated, since 97% of the examined children had no side effects with the exception of occasional drowsiness, pallor and myosis of short duration. Two of the children at the end of the test, had more severe symptoms 30 min after (deep asthenia, pallor and a further small blood pressure drop) which however, resolved after 4-6 h. No correlation was observed between the clinical picture and the drops in blood pressure and/or plasma cortisol in the children examined. We confirm the effectiveness of the clonidine test in the release of GH since in our study we observed no negative false subnormal responses.

Prednisone treatment in newly diagnosed type I diabetic children: 1-yr follow-up.

Thirty-one children suffering from type I diabetes mellitus were arranged at onset of the disease in two different groups. Group 1 was treated with oral prednisone (60 mg X m-2 X day-1 for 14 days, 30 and 15 mg X m-2 X day-1 for 7 days). Group 2 matched the control group. All patients were treated with continuous subcutaneous insulin infusion for the first 15 days of treatment, and then with two daily injections of a mixture of intermediate- and fast-acting insulin. All subjects were followed for 1 yr. Group 1 required more insulin than group 2 after 30 days (1.5 +/- 0.3 vs. 0.6 $ 0.2 U X kg-1 X day-1, P less than .001) and after 60 days (0.8 +/- 0.1 vs. 0.5 +/- 0.06 U X kg-1 X day-1, P less than .001). After 3 mo, both groups reached the lowest mean stable HbA1 level (8.4 +/- 0.4 and 8.3 +/- 0.4% group 1 and 2 respectively). Between the 2nd and 9th mo of follow-up, mean postbreakfast C-peptide concentration increased in both groups. The highest levels of fasting C-peptide were reached by group 1 after 90 days (0.77 +/- 0.32 nM) and group 2 after 60 days (0.34 +/- 0.09 nM). The largest partial remission (C-peptide 0.3 nM, insulin requirement less than 0.5 U X kg-1 X day-1 and no glycosuria) was observed in group 1 after 180 days (5 of 16 patients) and in group 2 after 60 days (5 of 15 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Empty sella in children with pituitary dwarfism: does it exist?

Empty sella is a descriptive term used to define an anatomoradiological entity characterized by penetration of cerebrospinal fluid (CSF) and subarachnoid space within the sella cavity. To clarify the relationship between empty sella and the endocrinological abnormalities frequently associated in pediatric patients, we examined the hormonal and radiological characteristics of 16 short children with empty sella. In all patients the diagnosis of empty sella was made by computerized tomography (CT) examination. In 5 of 16 patients a magnetic resonance imaging (MRI) study of the sellar region was performed. Growth hormone deficiency (GHD) was found in all 16 patients, hypothyroidism in 6 of 16, hyperprolactinemia in 1 of 16, gonadotropin deficiency in 4 of 11, low cortisol levels in 4 of 13 patients. None of our patients had a CT image of classical empty sella. MRI showed instead the presence of hypoplastic pituitary and disrupted stalk in all patients. In conclusion the endocrinological investigation revealed the presence of isolated GHD in 7 of 16 and multiple hormone defects in 9 of 16 of our patients. This situation is probably not related to a classical empty sella, but depends on a pituitary hypoplasia as the MRI study properly demonstrated.

In vivo studies with growth hormone (GH)-releasing factor and clonidine in rat pups: ontogenetic development of their effect on GH release and synthesis.

The demonstration that GH-releasing factor (GRF) stimulates GH synthesis and release in rat pups prompted studies to evaluate the effects on the same indices of clonidine (CLO), an alpha 2-adrenoceptor and potent GH secretagogue, purported to act in adult rats via GRF release. Our first aim was to ascertain whether CLO elicits GH release in rat pups via GRF, and if this is the case, to evaluate the ontogenetic development in 1- to 10-day-old pups of the GH response to acute CLO or GRF administration and, finally, the effects of short term CLO or GRF treatment on plasma and pituitary GH concentrations and on the GH response to an acute challenge with the homologous secretagogue. CLO (15 micrograms/100 g BW, sc) induced a clearcut GH rise in 10-day-old rats but not in pups pretreated with a specific anti-GRF serum. Moreover, unlike GRF (10(-8) M), CLO (10(-6) to 10(-5) M) did not stimulate GH release in vitro from anterior pituitaries of 10-day-old rats. In 1-day-old rats, neither CLO (15 micrograms/100 g BW, sc) nor GRF (20 ng/100 g BW, sc) stimulated GH release, whereas significant GH stimulation was elicited by GRF, but not CLO, in 5-day-old rats and by both secretagogues in 10-day-old rats. Short term treatment with CLO (15 micrograms/100 g BW, sc, twice daily) or GRF (20 ng/100 g BW, sc, twice daily) on postnatal days 1 through 5 did not modify either plasma or pituitary GH concentrations 14 h after the last drug administration, but did so when either secretagogue was administered on postnatal days 5 through 9. Finally, an acute challenge with GRF, but not with CLO, induced a further rise in the already elevated plasma GH levels of pups pretreated from postnatal day 5 through 9, but neither secretagogue did so in pups pretreated from postnatal days 1 to 5. Viewed together, these data indicate that in infant rats CLO releases GH via GRF release and that the somatotropes respond earlier to GRF (5 days) than the GRF-secreting structures do to alpha 2-adrenergic stimulation (10 days). Both GRF and CLO stimulate GH synthesis when administered repeatedly. However, whereas repeated GRF treatment has a priming effect on the somatotropes, CLO does not, probably because of down-regulation of hypothalamic alpha 2-adrenoceptors.

[Non-endocrine growth retardation. Diagnostic and therapeutic indications]. / I ritardi staturali non endocrini. Indicazioni diagnostiche e terapeutiche.

We analyze the most frequent conditions of non endocrine short stature divided into two groups by phenotypic criterion (dysmorphic or not). Furthermore we consider the different causes of short stature in relation to the appearance of stunted growth. The most recent etiopathogenetic advances in knowledge and the main auxologic features of each kind are reported. In the end we evaluate the current therapeutical measures and we analyse the usefulness of non specific treatments.