C. Pellini

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 agematched 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 mal-developed 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 dysembriogenic 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.

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.

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 · m−2 · day−1 for 14 days, 30 and 15 mg · m−2 · 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 · kg−1 · day−1, P < .001) and after 60 days (0.8 ± 0.1 vs. 0.5 ± 0.06 U · kg−1 · day−1, P < .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 <0.5 U · kg−1 · 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). We found no significant difference between the two groups in fasting and postbreakfast C-peptide levels, stable HbA1, and remission during 1-yr follow-up. Short-term prednisone therapy in newly diagnosed type I diabetic children does not considerably modify the natural history of the disease during the 1st yr.

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.

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.

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 (responded), while the remaining 60% did not (nonre-sponders). 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<0.025) higher in responders than in non responded. 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.

73 MR IMAGING (MRI) OF PITUITARY GLAND AND STALK IN MIOPATHIC GROWTH HORMONE DEFICIENCY (IGHD)

To search for the presence of morphostructural abnormalities of the hypothalamus - pituitary region in GHD children MRI was performed in 28 IGHD pts (21M, 7F, age 10.1±3.4, range 4.2-18) and in 15 healthy age matched controls (10M, 5F, age 8.3±2.9, range 4 to 12.4). Isolated GHD had been demonstrated in 19/28 pts, multiple pituitary hormones deficiency (MPHD) in 9/28; none had ADH deficiency. Hypothalamic or pituitaric deficiency was equally distributed in the two groups. We evaluated: presence, size, shape of the pituitary stalk; pituitary and sella volume calculated according to Di Chiro. MRI revealed that in 18/28 pts the pituitary stalk was separate from the gland (Group 1); in 14/18 pts the reurohypophysis was dislocated in the hypothalamic region; the pituitary and sella volumes were markedly reduced in all CHD pts compared with controls. No special endocrinological feature characterized the 2 groups.Conclusions: GHD pts frequently present some degree of abnormality of the hypothalamus-pituitary region; this picture is equally distributed between isolated GHD and MPHD pts. The observed dislocation of the neurohypophysis does not induce ADH deficiency.