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S Zucchini

Publications and source records attributed to S Zucchini.

At least 37 records · Page 2Linked to original sources
PubMed1995

Primary empty sella: differences and similarities between children and adults.

To identify possible differences between empty sella in children and adults we studied 43 subjects (age 13.6 +/- 5.4 years, range 4.1-27 years) with hypothalamic-pituitary disorders and empty sella at magnetic resonance imaging. Pituitary function, presence of non-endocrine symptoms, perinatal history, sellar volume, pituitary height, midline or intrasellar anatomical abnormalities were evaluated. Twenty subjects had isolated growth hormone deficiency, 17 multiple pituitary hormone deficiency and 6 puberty disorders (3 precocious puberty, 2 idiopathic delayed puberty, 1 Kallmann syndrome). The group with multiple pituitary hormone deficiency had a higher percentage of subjects with complete empty sella, i.e. pituitary height < 2 mm (p = 0.016), or intrasellar anatomical abnormalities (p = 0.0002) than the other groups. The subjects with puberty disorders had a mean sellar volume higher than the other groups (p < 0.05). Apart from pituitary dysfunction, symptoms of the empty sella syndrome were infrequent (9.3% of cases) in our subjects. The age of our subjects, the frequent association between empty sella and pituitary dwarfism and the non-enlarged sellae suggest a different aetiology, perhaps congenital, for empty sella in our subjects. As in adults, empty sella may be associated with both pituitary hypo- and hyperfunction.

Adolescent↗
PubMed1995

An 8-year follow-up of anti-insulin antibodies in diabetic children: relation to insulin autoantibodies, HLA type, beta-cell function, clinical course and type of insulin therapy.

In 105 children and adolescents with IDDM, insulin antibodies were detected as a percentage of radiolabelled insulin both at onset of disease and during the first 8 years of treatment. At diagnosis, 29 patients (27%) were insulin autoantibody positive (IAA+). An inverse relationship was found between IAA levels and age at diagnosis. No significant correlation was seen between IAA positivity and HLA antigens, while there was a negative correlation between IAA and C-peptide levels in the second year of the disease. The percentage of insulin antibody (IA) positive patients increased after insulin administration, with a maximum peak between the first and second year of the disease. The IA response to insulin therapy was similar in IAA+ and IAA- patients, while it was greater in younger children. No relationship was found between IA levels and haemoglobin A1c values, daily insulin requirement, HLA and early complications. No difference in either percentage of positivity or IA levels was seen in patients treated continually for the first 5 years of the disease with monocomponent porcine insulin or human insulin. A negative correlation was found between IA and C-peptide levels in the first and second years of the disease. In conclusion, we have shown that, even after many years of disease, neither IAA nor IA, induced in equal measures by current human insulin preparations, have significant effects on the clinical course of the disease.

Adolescent↗
PubMed1995

Role of magnetic resonance imaging in hypothalamic-pituitary disorders.

Improvement of MRI diagnostic accuracy in the study of the hypothalamic-pituitary region provides precise anatomic details. In pituitary dwarfism, MRI reveals severe sella/pituitary gland and stalk hypoplasia with or without posterior pituitary ectopia, and empty sella, and this more frequently in patients with multiple pituitary hormone deficiency. Two main hypotheses have been proposed to explain these findings: traumatic stalk transection during breech delivery, and abnormal embryonic development of the pituitary gland. The association between neuroradiological findings and type/severity of endocrine alteration has not yet been clarified. In diabetes insipidus, MRI findings are normal picture, posterior lobe not visible, and thickened stalk (as expression of preclinical/initial histocytosis). Patients with central precocious puberty or hypogonadotropic hypogonadism rarely show morphologic abnormalities (hamartoma of the tuber cinereum, partially empty sella). So far, MRI permits one to identify morphologic pictures in diseases previously considered 'idiopathic'.

Humans↗
PubMed1994

Molecular study of human growth hormone gene cluster in three families with isolated growth hormone deficiency and similar phenotype.

The growth hormone (GH) gene (hGH-N) cluster was analysed using polymerase chain reaction, Southern and polymorphism analysis in five patients (including two pairs of siblings) with extreme short stature and absence of GH secretion. Patients 1 and 2 (siblings) were homozygous for a large deletion removing four genes of the cluster: hGH-N, hCS-L, hCS-A and hGH-V. Both siblings produced high anti-GH antibody levels in response to exogenous GH therapy, followed by growth arrest a few months after starting replacement therapy. In patient 3 we detected a heterozygous deletion which involved three genes of the cluster (hCS-A, hGH-V, hCS-B) and left an intact hGH-N gene. Direct sequencing of hGH-N specific amplified fragments excluded the presence of any point mutations in exons and splicing regions. In patients 4 and 5 (sisters) our study did not demonstrate any gene deletions. Analysis of polymorphic restriction patterns in this family demonstrated that both sisters inherited the same alleles from the father but different alleles from the mother, suggesting that the defect was not linked to the hGH-N gene. These results confirm the difficulty of clinical identification of subjects with hGH-N deletion and underline the importance of DNA analysis in patients with absence of GH secretion and extreme growth retardation.

Adolescent↗
PubMed1994

Empty sella in children and adolescents with possible hypothalamic-pituitary disorders.

Several computed tomographic scan studies have described empty sellae in children with hypothalamic-pituitary disorders. Magnetic resonance imaging, however, is a more precise technique for visualizing the intrasellar content, such as the stalk and pituitary lobes. Using magnetic resonance imaging, we studied 339 children and adolescents (mean age +/- SD, 12.7 +/- 4.5 yr) with possible hypothalamic-pituitary disorders to ascertain the frequency of primary empty sella and examine its relationships with other intrasellar abnormalities, pituitary function, and adverse perinatal events. One hundred and ninety-three patients had isolated GH deficiency, 43 had multiple pituitary hormone deficiency, 10 had diabetes insipidus, 17 had hypogonadotropic hypogonadism, 5 had idiopathic delayed puberty, 47 had precocious puberty, and 24 had other hypothalamic pituitary disorders of hyperfunction. One tenth (10.9%) of the patients (37 cases) had empty sella, with a marked variation of incidences among the disorders listed above. A statistically higher frequency of subjects with empty sellae was found only in patients with multiple pituitary hormone deficiency. Patients with and without empty sellae were not different in regard to age or sex. The incidence of empty sella in the various groups of patients was as follows: isolated GH deficiency, 8.8% (17 cases); multiple pituitary hormone deficiency, 34.9% (15 cases); hypogonadotropic hypogonadism, 5.9% (1 case); idiopathic delayed puberty, 40% (2 cases); and precocious puberty, 4.2% (2 cases). No patients with isolated diabetes insipidus or other hypothalamic-pituitary disorders had empty sellae. In the patients with empty sellae, abnormalities of the stalk or posterior lobe were found in 1 patient with isolated GH deficiency (5.9%), 13 patients with multiple pituitary hormone deficiency (86.7%), and no patients with puberty disorders. Likewise, adverse perinatal events were found only in 1 patient with isolated GH deficiency and 9 patients with multiple pituitary hormone deficiency. These findings suggest that empty sella is not rare in children and adolescents evaluated for hypothalamic-pituitary disorders, particularly if there is multiple pituitary hormone deficiency. Empty sella can be found regardless of abnormalities of the stalk and posterior lobe, and adverse perinatal events do not seem to be the primary etiological factor. Empty sella is usually associated with pituitary hypofunction, but it can be found in patients with hyperfunction of the hypothalamic-pituitary-gonadal axis.

Adolescent↗
PubMed1994

Value and limits of pharmacological and physiological tests to diagnose growth hormone (GH) deficiency and predict therapy response: first and second retesting during replacement therapy of patients defined as GH deficient.

There is currently a debate about the use of pharmacological and physiological tests to define GH deficiency and predict response to GH therapy. In addition, a good response to therapy has also been described in subjects without GH deficiency. For further information, we reevaluated GH secretion during replacement therapy in a group of children defined as GH deficient and examined response to therapy in the subjects subdivided according to secretion. One hundred eighty four children (113 boys and 71 girls) initially diagnosed with GH deficiency by means of pharmacological (peak < 8 micrograms/L after arginine and L-dopa tests) and physiological tests (mean nocturnal concentration < or = 3.3 micrograms/L during sleep test) underwent the same tests 2.8 +/- 1.1 yr after start of GH therapy. Sixty eight patients were retested 1.5 +/- 0.4 yr after first retesting. At diagnosis 122 subjects had pathological pharmacological and physiological tests (group A), 30 subjects normal sleep test with pathological pharmacological tests (group B), and 32 subjects pathological sleep test with normal pharmacological tests (group C). At diagnosis 140 subjects were prepubertal and 44 pubertal. To evaluate response to therapy in relation to GH secretion at diagnosis and at both retestings, a number of auxological parameters were calculated during treatment. At first retesting, 107 subjects (58.1%) changed initial group of diagnosis, 34 of whom (18.5%) presented normal secretion in both pharmacological and physiological tests (group D). At second retesting, 31 of the 68 subjects reexamined (45.6%) changed first test results, and 33 (48.5%) reverted to the initial group of diagnosis; none of the 6 subjects of group D maintained normal secretion. Although the percentage of normalized subjects was higher in pubertal subjects (36.4%; P = 0.0003) than prepubertal subjects (8.9%), puberty did not prevent a reduction of secretion in some subjects. Response treatment during the first year of therapy was similar in the various groups. GH secretion seems to change in both prepubertal and pubertal children diagnosed with GH deficiency when pharmacological and physiological tests are repeated over time. Moreover, such tests may not represent a reliable tool for predicting response to treatment. GH secretion normalization at retesting may not necessarily represent the end of a transient secretory defect.

Adolescent↗
PubMed1993

Inhibition of human immunodeficiency virus reactivation from latency by a tat transdominant negative mutant.

A BK virus (BKV) expression vector, specific for human cells, was engineered to express antisense human immunodeficiency virus type 1 (HIV-1) tat cDNA (tat-AS) or a tat mutant in cysteine 22 (tat22). Cysteine residues in the cysteine-rich domain of tat are necessary for tat transactivation of the HIV-1 long terminal repeat (LTR). Both the AS tat and the tat mutant significantly inhibited transactivation by tat when assayed in cells cotransfected with an expression vector where the reporter gene for chloramphenicol acetyl transferase was driven by the HIV-1 LTR. Infection of Jurkat cell clones stably expressing tat22 (Jurkat/tat22) or tat-AS (Jurkat/tat-AS) with HIV-1 did not show differences in virus titer in comparison to HIV-1-infected control cells. However, in two Jurkat/tat22 cell clones, entrance of HIV-1 into latency was accelerated significantly and reactivation of HIV-1 from latency induced by tumor necrosis factor-alpha (TNF-alpha) or tat was blocked. These results suggest that, in a combined and integrated approach to the treatment of acquired immunodeficiency syndrome (AIDS), anti-tat genetic therapy could be successfully applied to maintain virus in latency, thereby extending the duration of the asymptomatic phase preceding full-blown AIDS.

BK Virus↗
PubMed1992

Magnetic resonance imaging of the pituitary area in children treated for acute lymphoblastic leukemia with low-dose (18-Gy) cranial irradiation. Relationships to growth and growth hormone secretion.

OBJECTIVE: To determine the effects of 18-Gy cranial irradiation on growth, growth hormone (GH) secretion, and pituitary magnetic resonance imaging in children who underwent previous irradiation for treatment of acute lymphoblastic leukemia. DESIGN: Clinical survey. SETTING: Department of Pediatrics of the University of Bologna (Italy). PATIENTS: Ten boys and 18 girls who were treated for acute lymphoblastic leukemia; median age at diagnosis was 3.1 years and at the end of follow-up was 11.5 years. MEASUREMENTS AND RESULTS: Height was periodically measured from diagnosis until the end of follow-up, when GH secretion study and magnetic resonance imaging were performed. The mean height SD score was significantly lower than at diagnosis only at the end of treatment. Nocturnal mean GH concentration and GH response to pharmacological tests (arginine and levodopa [L-dopa]) were pathological in 22 cases (81.5%) and 18 cases (64.3%), respectively. Sixteen cases (59.2%) had a blunted GH release to the three tests. Mean pituitary anterior lobe height was reduced and seven subjects (25%) showed an empty sella. CONCLUSIONS: Cranial irradiation with 18 Gy does not seem to influence the growth pattern of most children who are treated for acute lymphoblastic leukemia, despite severe impairment of GH secretion and morphological abnormalities of the sellar area. However, a follow-up until final height is necessary.

Adolescent↗
PubMed1992

Pitfalls in diagnosing impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient.

Possible causes of error in the diagnosis of isolated GH deficiency are the variability of GH response to repeated tests, the existence of transient GH deficiencies, and the low GH levels found in short statured children with delayed puberty. Sixty-three patients with variously expressed GH deficiency were retested (1 sleep test and 2 pharmacological tests) after 1-3.9 yr of GH therapy (dose, 15 U/m2.week). Forty-eight subjects had arginine, L-dopa, and sleep tests (mean serum GH concentration) twice, while 15 had only arginine and L-dopa tests. All patients were retested 1 month after withdrawal from therapy. The criteria used to subdivide the patients were pubertal development and response to pharmacological and sleep tests at first diagnosis and on retesting. The initial diagnosis in 33 subjects (52.4%) was not confirmed, and 13 (20.6%) were no longer deficient on retesting. The percentage of normalization was high for the sleep test (43.9%), lower for the pharmacological test (24.5%), and lower still (12.9%) for pharmacological and sleep tests considered together. While none of the 28 subjects who remained prepubertal at retesting normalized in any of the tests, 13 of the 35 subjects retested during puberty did. When normalization was observed in pubertal subjects, it occurred predominantly in the sleep test. Growth velocity and height age/bone age increment ratio after the first year of therapy were no different for the groups of subjects classified according to GH secretion on retesting. Our study demonstrates that a number of children diagnosed as GH deficient do not have a true deficiency. However, such a diagnostic error seems to have little effect, at least in the first year of therapy, on the effectiveness of GH treatment.

Adolescent↗
PubMed1990

Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance.

Evaluation of the sellar area was performed with magnetic resonance imaging in 101 patients (age range 0.8-27 years) with hypopituitarism, isolated diabetes insipidus, hypogonadotrophic hypogonadism, and central precocious puberty. The hypopituitary patients (n = 70) included multiple pituitary deficiency (n = 23), pituitary deficiency with diabetes insipidus (n = 5), and isolated growth hormone deficiency (n = 42). The patients with multiple pituitary deficiency showed pathological morphological findings in all cases, with stalk and posterior lobe always involved. The group with associated diabetes insipidus had abnormal stalk in four of five cases and posterior lobe not visible in all cases. Only five of 42 (12%) patients with isolated growth hormone deficiency had abnormalities of the sellar area. In two out of four patients with isolated diabetes insipidus posterior lobe was not seen. All patients with hypogonadotrophic hypogonadism (three with Kallmann's syndrome, one Prader-Willi syndrome, and two idiopathic hypogonadism) appeared normal. In precocious puberty (n = 21) the three patients with onset of symptoms before age 2 years exhibited a hypothalamic hamartoma, whereas in the others with onset of puberty between age 2 and 7 the magnetic resonance image was normal in 17 of 18 patients. The probability of finding a pathological magnetic resonance image was considerably high in our patients with multiple pituitary deficiency, isolated diabetes insipidus, and precocious puberty with very early onset of symptoms. On the contrary, purely functional abnormality is suggested in most patients with isolated growth hormone deficiency, hypogonadotrophic hypogonadism, and precocious puberty with later onset of symptoms.

Adolescent↗
PubMed1990

Variability of growth hormone response to pharmacological and sleep tests performed twice in short children.

Forty-nine children with short stature (age range, 4.1-15.9 yr) were examined. Twenty-four (group 1) were submitted twice to an arginine and a sleep test (12-h overnight GH profile). Twenty-five patients (group 2) were submitted twice to an arginine and L-dopa test. Coefficients of variation were calculated between both the results of pharmacological (peak and area under the curve) and sleep tests [mean GH concentration (MGHC), peak, area under the curve, number of peaks above 5 micrograms/L, and peak area]. In group 1 the coefficient of variation of sleep test parameters was significantly lower than that of pharmacological tests (P less than 0.01 to less than 0.001). In the sleep test the area under the curve and MGHC were the most constant parameters. Group 2 showed no difference between the coefficients of variation of the two pharmacological tests. Considering groups 1 and 2 together, the coefficients of variation of the sleep test, in particular the MGHC and area under the curve, were lower than those of the two pharmacological tests. Eight of 24 subjects in group 1 showed a low GH level in 1 series of tests, and a normal level in the other series. Five of 18 subjects in group 2 showed an abnormally low GH response to the arginine and L-dopa tests and a normal response to the 2 repeated tests. Therefore, to prevent an erroneous interpretation of the GH test results, it is very important to perform a sleep test and repeat it whenever GH secretion seems to be deficient or at the lower limits of normalcy.

Adolescent↗
PubMed1988

Intravascular intrauterine transfusion for severe erythroblastosis fetalis using different techniques.

Over a 3-year period, 44 ultrasound-guided intravascular transfusions were performed between 18 and 32 weeks on 15 patients with severe erythroblastosis fetalis due to Rh immunization. In 4 fetuses, the first transfusion was performed before 20 weeks, in 6 between 20 and 25 weeks and in the remaining 5 between 25 and 31 weeks. Eight of the 15 fetuses were hydropic at the time of referral. Five transfusions were done in the intrahepatic umbilical vein, 6 were simple transfusions via percutaneous umbilical cord puncture, and 33 were partial exchange. There were 4 intrauterine deaths before 26 weeks, despite successfully performed transfusions: 3 of these fetuses were severely hydropic, while in the remaining fetus hydrops had been reversed in utero. Following delivery by cesarean section at 32 weeks of gestation, 1 of the neonates developed respiratory distress syndrome and died 17 h after birth. The overall survival rate was 67% (10 of 15 cases): 4 of the 8 hydropic fetuses (50%) and 6 of the 7 nonhydropic fetuses (83%) were alive at birth and survived the perinatal period. Three of the 5 losses occurred among the first 4 cases, while in the last 11 cases the survival rate increased to 82% (9 of 11).

Blood Transfusion, Intrauterine↗
PubMed1986

Somatomedin-C levels related to gestational age, birth weight and day of life.

Capillary blood samples on filter paper were assayed by means of an RIA method (Kit Nichols Institute USA) from 1096 newborns divided into full term, preterm and small-for-date infants. The somatomedin-C (Sm-C) mean value, which did not differ in the three groups, was 0.15 +/- 0.09 IU/ml. One hundred and ten (10%) showed Sm-C disc values less than or equal to 0.075 IU/ml, the minimum value measurable by our method. The day of life and birth weight had a significant influence on Sm-C levels. Gestational age did not have any significant effect. No significant interaction was found among the parameters considered. All the groups presented a progressive increase of Sm-C. Unlike preterm and small-for-date infants, in full term infants the latter increase seemed already to be evident from 5th day of life and reached higher levels from the 7th day of life onwards. In conclusion, Sm-C rates were reduced in the neonatal phase of life, but showed a tendency to rise later.

Age Factors↗
PubMed1986

Relationships between growth factors (somatomedin-C and growth hormone) and body development, metabolic control, and retinal changes in children and adolescents with IDDM.

We used the radioimmunoassay (RIA) method to determine somatomedin-C (SmC) basal values in 59 diabetic children and adolescents (20 prepubertal and 39 pubertal subjects; age range 2.75-20.16 yr; duration of diabetes 0.08-15.83 yr) and in 274 control subjects. In comparing diabetic subjects with controls, we considered only those 50 diabetic subjects who were age matched with the controls, i.e., those not over 16 yr chronological age. SmC basal levels in pubertal diabetic patients were no different from those of pubertal age-matched control children, whereas in prepubertal diabetic patients SmC was significantly lower than in the respective control children (P less than .001). No correlation was found between the z score for SmC (i.e., the number of standard deviations each SmC level is from the age- and sex-normalized mean) and duration of disease, velocity standard deviation score, severity of fluoroangiographic retinal changes, basal C-peptide values and HbA1 levels. No differences were encountered in mean SmC and SmC z-score values in the separate groups of poorly, fairly, and well-controlled diabetic children, in the groups with and without residual pancreatic activity, and in the group with and without retinal changes. In 16 of the pubertal diabetics and in 15 pubertal controls, serum glucose, growth hormone (GH), and SmC concentrations were determined during the night. The integrated nocturnal secretion of SmC was no different in diabetics than in controls, whereas the integrated nocturnal secretion of GH was significantly (P less than .025) higher in diabetics than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Differences in somatomedin-C between short-normal subjects and those of normal height.

We evaluated basal somatomedin-C (SmC) levels in 98 subjects 2 to 16.6 years of age, with height less than 3rd centile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height greater than 10th centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (greater than 8 ng/ml) in at least one of three tests: arginine, L-dopa, and sleep. In control subjects, there was a significant positive correlation between SmC levels and chronologic age, bone age, and pubertal stage (pubic hair, breast or testicular volume). The same correlations were present in short-normal subjects, but SmC levels were significantly lower than in normal children. The percentage of subjects with very low SmC values (less than or equal to 0.25 IU/ml in those older than 6 years, and less than 0.1 IU/ml in those younger than 6 years) was higher in the short-normal group of children older than 6 years. In growth-retarded subjects, SmC values were significantly higher (P less than 0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response only during sleep. We conclude that short-normal subjects have, on average, low SmC values, which might indicate insufficient GH release. Therefore, current criteria to define GH deficiency and children needing treatment may be too restrictive.

Adolescent↗
PubMedDate not supplied

Modifications of metabolic control in type 1 diabetic children and adolescents: experience over the last 20 years.

The aim of this retrospective study was to verify whether the daily number of insulin injections could have affected metabolic control in 181 unselected diabetic patients (age 0.66-14.75 yr at onset of diabetes) followed in our clinic from the 1970s to the 1990s. They were evaluated regularly since onset of disease for a mean follow-up period of 6.8 years. The factor with the greatest effect on HbA1c levels was the year of disease onset, which was negatively correlated with HbA1c independently of the daily number of injections and disease duration. Disease duration showed an effect on metabolic control only in the first 5 years of disease. Daily insulin injections affected metabolic control above all as regards 1 vs 2 or more injections. Regarding the change in insulin regimen from 2 to 3-4 injections, there was an improvement in metabolic control in patients with HbA1c > 9% and a worsening in those with HbA1c < 7%/ After the first 5 years of the disease HbA1c levels were higher in adolescent patients than in both younger and older patients. In conclusion, increasing the daily number of injections does not seem in itself capable of eliciting marked improvement in metabolic control, as in our young diabetic patients in the last decade. Multiple insulin injection therapy seems to be mostly indicated for patients with poor control and for adolescents.

Adolescent↗
PubMedDate not supplied

Unusual magnetic resonance imaging findings of the sellar region in subjects with hypopituitarism: report of 4 cases.

Out of 323 consecutive growth hormone deficient patients who underwent magnetic resonance imaging (MRI), we describe the clinical and neuroradiological characteristics of four patients in whom MRI revealed unusual pictures of the sellar area. They were selected as unique in their morphological picture and representative of rare conditions. At presentation all subjects had short stature, growth hormone (GH) deficiency and complex phenotypical abnormalities. Patient 1. Female affected by vaginal atresia and sinus urogenitalis, polydactyly and syndactyly with Y-shaped metacarpals. MRI at age 11.2 years revealed normal pituitary, but hypothalamic mass occupying the suprasellar and interpeduncular cistern. The diagnosis of Hall-Pallister syndrome was made. Patients 2 and 3. Two sisters with a history of epilepsy both showing mild intellectual deficiency, midface hypoplasia and ectodermal dysplasia. MRI at age 8 and 12 years respectively displayed in both cases a round hypointensity protruding from the dorsum sellae into a normal pituitary. The diagnosis was sellar spine. Patient 4. Male with a history of postnatal hypoglycemia showing microphallus and clinical features of severe hypopituitarism. Hormonal evaluation at age 8 months confirmed multiple pituitary hormone deficiencies and MRI at age 6 years showed absent anterior lobe, rudimentary stalk and posterior lobe ectopia. The diagnosis was pituitary aplasia. The patients described show that MRI in pituitary dwarfs can reveal unusual intrasellar findings and allow the correct diagnosis of rare syndromes. Our patients also demonstrate the wide variability in the association of hypopituitarism with midline congenital abnormalities and the possible combination with complex syndromes.

Abnormalities, Multiple↗