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Biomedical subjects

C de Sanctis

Publications and source records attributed to C de Sanctis.

At least 19 recordsLinked to original sources
PubMed2003

Pubertal development in patients with McCune-Albright syndrome or pseudohypoparathyroidism.

Gain or loss of function mutations of the GNAS1 gene lead to McCune-Albright syndrome (MAS) or pseudohypoparathyroidism Ia (PHP-Ia), respectively. Patients with MAS, caused by a post-zygotic missense mutation leading to constitutive activation of Gs alpha, suffer from gonadotropin-independent precocious puberty, and delayed or incomplete sexual development and reproductive dysfunction is found in women with PHP-Ia, an inherited disorder caused by deficient expression or function of the Gs alpha protein. In females with MAS, 50% developed precocious puberty by the age of 4 years, the remaining between 4 and 8 years. Peripheral precocious puberty is often atypical and characterized by alternate periods of rapid progression and regression of pubertal development; menstrual bleeding may occur before breast development. Ovarian cyst growth and regression is often described as a sign of ovarian follicle hyperactivation. Notwithstanding this clinical heterogeneity, a subset of patients with MAS develop relentlessly progressive precocious puberty ultimately resulting in premature epiphyseal fusion and reduced adult stature. Long-term information on reproductive function has been obtained in females: some patients had regular menses without ovarian cysts on pelvic US scan, whereas others were oligomenorrheic and showed recurrent ovarian cysts. In males with MAS, precocious puberty occurred in three patients between 4 and 9 years of age. In one patient, long-term follow-up demonstrated normal plasma testosterone and gonadotropin values at the age of 17 years. On testicular sonography, multiple hyperechogeneic spots were found in both testicles (snow-storm appearance). Female patients with PHP-Ia were oligomenorrheic or amenorrheic; more than half had delayed or incomplete sexual development, They were mildly hypoestrogenic with normal to slightly elevated serum gonadotropin levels. These clinical and biochemical findings indicate partial resistance of the theca and granulosa cells of the ovary to gonadotropins due to deficient Gs alpha activity. Responsiveness might be sufficient to promote some degree of follicular development and steroid secretion, but insufficient to induce ovulation

Amenorrhea↗
PubMed2002

Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia.

Bone fibrous dysplasia is one of the main features of McCune-Albright syndrome, a rare genetic condition caused by constitutive activating mutations of Gs-protein and defined by skin dysplasia, bone fibrous dysplasia, and autonomous multiple endocrinopathies. Raised serum alkaline phosphatase (ALP) and urinary hydroxyproline levels indicating bone metabolic hyperactivity have been reported in these patients. Encouraging therapeutic results have been achieved, mainly in adults, with pamidronate, an aminobisphosphonate. In this study we investigate newer bone metabolic indices in a cohort of 11 children and adolescents treated with pamidronate. Tenfold increases of bone ALP and urinary pyridinoline cross-links were found and osteocalcin levels were twofold higher compared with reference values. After treatment, significant decreases in bone ALP and cross-links (Wilcoxon test P < 0.06) were found. Bone mineral density (BMD) significantly increased during treatment. There were signs of radiological healing as thickening of the cortical bone was found in some cases.

Adolescent↗
PubMed2002

Short children with familial short stature show enhancement of somatotroph secretion but normal IGF-I levels.

The aim of the present study was to evaluate the GH status in children with familial, idiopathic short stature (FSS). To this goal we evaluated the GH response to GHRH (1 microg/kg iv) + arginine (ARG) (0.5 g/kg iv) test which is one of the most potent and reproducible provocative tests of somatotroph secretion, in 67 children with FSS [50 boys and 17 girls, age 10.8+/-0.4 yr, pubertal stages I-III, height between -3.6 and -1.6 standard deviation score (SDS), target height <10 degrees centile, normality of both spontaneous and stimulated GH secretion as well as of IGF-I levels]. The results in FSS were compared with those in groups of children of normal height (NHC) (42 NHC, 35 boys and 7 girls, age 12.0+/-0.5 yr, pubertal stages I-III, height between -1.3 and 1.4 SDS, height velocity standard deviation score (HVSDS)>25 degrees centile, GH peak >20 microg/l after GHRH+ARG test, mean GH concentration [mGHc]>3 microg/l) and children with organic GH deficiency (GHD) (38 GHD, 29 boys and 9 girls, age 11.2+/-3.7 yr, pubertal stages I-III, height between -5.7 and -1.3 SDS, GH peak <20 microg/l after GHRH +ARG test, mGHc <3 mg/l). Basal IGF-I levels and mGHc were also evaluated in each group over 8 nocturnal hours. IGF-I levels in FSS (209.2+/-15.6 microg/l) were similar to those in NHC (237.2+/-17.2 microg/l) and both were higher (p<0.0001) than those in GHD (72.0+/-4.0 microg/l). The GH response to GHRH +ARG test in FSS (peak: 66.4+/-5.6 microg/l) was very marked and higher (p<0.01) than that in NHC (53.3+/-4.5 microg/l) which, in turn, was higher (p<0.01) than in GHD (8.2+/-0.8 microg/l). Similarly, the mGHc in FSS was higher than in NHC (6.7+/-0.5 microg/l vs 5.1+/-0.7 microg/l, p<0.05) which, in turn, was higher than in GHD (1.5+/-0.2 microg/l, p<0.0001). In conclusion, our present study demonstrates that short children with FSS show enhancement of both basal and stimulated GH secretion but normal IGF-I levels. These findings suggest that increased somatotroph function would be devoted to maintain normal IGF-I levels thus reflecting a slight impairment of peripheral GH sensitivity in FSS.

Arginine↗
PubMed2002

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Acromegaly↗
PubMed2002

Pamidronate treatment in bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.

Thirteen patients with McCune-Albright syndrome (MAS) and bone fibrous dysplasia (BFD) have been treated for 2-6 years with pamidronate, an aminobisphosphonate which inhibits osteoclastic function. MAS is a rare genetic condition caused by constitutive activating mutations of the Gs protein and manifests with skin dysplasia, bone fibrous dysplasia, and multiple endocrinopathies. Raised serum alkaline phosphatase and urinary hydroxyproline have been reported in these patients, indicating bone metabolic hyperactivity. Encouraging therapeutic results have been achieved with pamidronate, mainly in adults. In our study, treatment reduced bone pain, fracture rate and metabolic indices of bone turnover, in particular significantly decreased bone alkaline phosphatase and cross-links (Wilcoxon test; p <0.06), and increased bone mineral density (DEXA). Signs of healing, such as thickening of the cortical bone, were found in some patients. Three patterns of MRI were found: homogeneous hypointense fibrous tissue, 'dotted' hypointense fibrous tissue, and hyperintense cystic images. Pamidronate treatment can be considered a favorable therapeutic option for patients with MAS.

Adolescent↗
PubMed2000

Reduction of the pituitary GH releasable pool in short children with GH neurosecretory dysfunction.

OBJECTIVES: The classical 'GH neurosecretory dysfunction' (GHNSD) refers to slowly growing children with normal GH responses to classical provocative tests but impaired spontaneous GH secretion over 24 h frequently leading to low IGF-I levels. Thus it has been assumed that these subjects have insufficiency of spontaneous GH secretion due to neuroendocrine abnormalities in spite of a normal releasable pool of GH. However, classical provocative tests do not reliably assess the maximal somatotroph capacity; thus it is still unclear if the GH pool is really preserved or not. GHRH + arginine test is more potent than the classical tests and evaluates the maximal secretory capacity of somatotroph cells. The GH response to this stimulus is reproducible and also independent of age and puberty. DESIGN AND PATIENTS: We studied the GH response to GHRH (1 microgram/kg iv) + arginine (ARG, 0.5 g/kg iv) in 19 short children with GHNSD (14 boys and 5 girls, age: 12.1 +/- 0.7 years, pubertal stages I-III, HV-SDS between -1.6 and -4.9; GH peak > 10 micrograms/l after classical stimuli but mean GH concentration (mGHc) < 3 micrograms/l). The results in GHNSD were compared with those in 38 short children with idiopathic or organic severe GHD (GHD, 29 boys and 9 girls, age: 11.2 +/- 0.6 years, pubertal stages I-III, HV-SDS between -1.8 and -4.4; GH peak < 10 micrograms/l after 2 classical provocative tests) and in 83 children with normal or familial short stature (NC, 59 boys and 24 girls, age: 11.5 +/- 0.3 years., pubertal stages I-III; HV-SDS > 25th centile, normal IGF-I levels). RESULTS: Mean IGF-I levels in GHNSD (121.9 +/- 20.3 micrograms/l) were lower (P < 0.001) than those in NC (270.3 +/- 13.8 micrograms/l) but higher (P < 0.001) than those in GHD (72.0 +/- 4.0 micrograms/l). The mean GH concentration (mGHc) in GHNSD (2.1 +/- 0.1 micrograms/l) was lower (P < 0.01) than that in NC (4.9 +/- 0.5 micrograms/l) but higher (P < 0.01) than that in GHD (1.5 +/- 0.2 micrograms/l). On the other hand, the mean peak GH response to GHRH + ARG in GHNSD (43.7 +/- 3.7 micrograms/l) was markedly higher (P < 0.001) than that in GHD (8.2 +/- 0.9 micrograms/l) but significantly lower (P < 0.01) than that in NC (60. 4 +/- 2.7 micrograms/l). All GHD patients had peak GH responses to GHRH + ARG below the 3rd centile limit of normality (20 micrograms/l), while all GHNSD patients had peak GH responses within the normal range. No significant correlation was found between GH peak after GHRH + ARG, mGHc and IGF-I levels in each group. CONCLUSION: Our study demonstrates that short children with 'GH neurosecretory dysfunction' show reduction in the GH releasable pool evaluated by the provocative and potent GHRH + arginine test. However, the peak GH response to a single GHRH + arginine test in GH neurosecretory dysfunction is always within the normal range indicating that this test as well as classical stimuli does not distinguish normal subjects from GH neurosecretory dysfunction.

Arginine↗
PubMed2000

Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome.

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.

Adolescent↗
PubMed1998

Cryptorchidism: medical and surgical treatment in the 1st year of life.

Since cryptorchidism can cause infertility and early orchiopexy can improve fertility, we tried to determine whether medical and surgical treatment in the 1st year of life can improve testicular fertility. We concluded that this is the best time to treat cryptorchid tests.

Administration, Intranasal↗
PubMed1997

Early hormonal and surgical treatment of cryptorchidism.

PURPOSE: We investigated the efficacy of early gonadotropin treatment of cryptorchidism for promoting testicular descent and ameliorating testicular histology. MATERIALS AND METHODS: We treated 319 cryptorchid testes in 281 boys 4 months to 3 years old with luteinizing hormone-releasing hormone and human chorionic gonadotropin sequential therapy. Surgery was done on the 207 testes that did not respond to medical treatment. Microscopic biopsies were performed in 134 of these 207 testes. Histological findings were compared to those of 30 cryptorchid testes in boys younger than 1 year who underwent surgery without previous hormonal treatment. RESULTS: Combined luteinizing hormone-releasing hormone and human chorionic gonadotropin treatment induced scrotal descent of a percentage of cryptorchid testes depending on clinical position. Therapeutic success was greater when testes were in a lower position and results were not age dependent. Hormonal treatment of cryptorchidism during the first year of life stimulated spermatogonia maturation. CONCLUSIONS: When administered at the end of age 6 months, hormonal treatment can be considered an effective and timely substitution for gonadotropin and testosterone insufficiency in cryptorchid infants. Therefore, we recommend this therapeutic procedure combined with surgery in the first year of life.

Age Factors↗
PubMed1993

Combined therapy with LHRH and HCG in cryptorchid infants.

In 238 boys with cryptorchidism, between the ages of 4 and 48 months, luteinizing hormone releasing hormone (LHRH) was administered as nasal spray 1.2 mg/day for 4 weeks. The nonresponders received human chorionic gonadotropin (HCG) 500 I.U. i.m. three times a week for 3 weeks. With the combined treatment 37.8% of testes descended into the scrotum. Testicular descent occurred more often in patients whose testes were located in a lower position. Histological findings indicated a reduction in the number and maturation of germ cells. A clear improvement of germ cells trophism was observed in boys hormonally treated and operated on before the 12th month of life. Early administered combined treatment with LHRH and HCG can be considered as a substitution of the gonadotropins insufficiency manifested by most cryptorchid infants in the first months of life.

Administration, Intranasal↗
PubMed1990

[Diagnosis of ambiguous genitalia].

Diagnosis in patients with ambiguous genitalia is based on various investigations. Simple genital examination is not sufficient to attribute sex. Scarce androgenization in a male patient or marked androgenization in a female may both lead to the same stages of genital ambiguity according to Prader. It is important to get information about genital ambiguity in the family, drug consumption during gestation and signs of virilization in pregnant mothers. External genital findings must be integrated by visualization of urogenital sinus by X-rays, ultrasounds and endoscopy. Furthermore, hormonal evaluations on plasma and 24 hours urines allow diagnosis of some disorders of adrenal and gonadal steroidogenesis. To define genetic sex, chromosomal examination is required to integrate X chromatine investigation and fluorescent staining of Y chromosome. Evaluation of psychosexuality in patients who have already got gender identity is mandatory.

Disorders of Sex Development↗