Aurora Natalia Rossodivita

Ovarian volume and gluco-insulinaemic markers in the diagnosis of PCOS during adolescence

To evaluate the role of mean ovarian volume (MOV) in the diagnosis of polycystic ovary syndrome (PCOS) during adolescence, and its relationship with metabolic and endocrine parameters.

Chromosome 9p deletion syndrome and sex reversal: novel findings and redefinition of the critically deleted regions

Deletions of the short arm of chromosome 9 are associated with two distinct clinical entities. Small telomeric 9p24.3 deletions cause genital anomalies in male subjects, ranging from disorder of gonadal sex to genital differentiation anomalies, while large terminal or interstitial deletions result in 9p‐malformation syndrome phenotype. The critical region for non‐syndromic 46,XY sex reversal was assigned to a 1 Mb interval of chromosome 9p, extending from the telomere to the DMRT genes cluster. The 9p‐syndrome was assigned to bands 9p22.3p24.1, but a phenotypic map has not been established for this condition, probably because of the lack of detailed molecular and/or phenotypic characterization, as well as frequent involvement of additional chromosome rearrangements. Here, we describe a unique patient with a small isolated 9p terminal deletion, characterized by array‐CGH and FISH, who shows a complex phenotype with multiple physical anomalies, resembling the 9p‐syndrome, disorder of sex development with gonadoblastoma, congenital heart defect and epilepsy. The observed deletion includes the 46,XY sex‐reversal critical region, excluding the region so far associated with the 9p‐syndrome. Genotype–phenotype correlations are tentatively established comparing our patient to seven other previously reported males with isolated terminal 9p deletions, finely defined at a molecular level. Our observations expand the 9p deletion clinical spectrum, and add significantly to the definition of a 9p‐syndrome critical region.

Functional analysis of two rare CYP21A2 mutations detected in Italian patients with a mildest form of congenital adrenal hyperplasia

Background  More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21‐hydroxylase gene (CYP21A2) mutations. Most of these mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5–10% of 21‐hydroxylase deficiency alleles.

A novel MEN1 frameshift germline mutation in two Italian monozygotic twins

Abstract Background: This report describes clinical, biochemical and molecular findings regarding two Italian monozygotic twins carrying a novel multiple endocrine neoplasia type 1 (MEN1) mutation inherited from their mother. Methods: Clinical, biochemical and genetic evaluations of the above-mentioned family members were performed. Results: All three members were heterozygous for a deletion involving the first nucleotide at codon 98 in exon 2 of the MEN1 gene, which results in early termination of the protein. The clinical phenotypes were as follows: one out of the two twins suffered from insulinoma and hyperparathyroidism, while the second one was asymptomatic. Furthermore, the mother suffered from hyperparathyroidism, as well as from hypergastrinemia for several years before the daughter was diagnosed of MEN-1. Conclusions: We describe a family with a new heterozygous mutation (g.292delC) in the MEN1 gene not described previously. The mutation leads to a truncated protein without activity, explaining the clinical picture of this family. Clin Chem Lab Med 2008;46:824–6.

Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure

Costello syndrome is a rare multisystem disorder caused by mutations in the proto-oncogene HRAS. Failure to thrive is one of its cardinal clinical features. This study documents that individuals with Costello syndrome have increased resting energy expenditure. We speculate this could be one of the potential mechanisms causing failure to thrive.

Insulin and GH secretion in adolescent girls with irregular cycles: Polycystic vs multifollicular ovaries

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15±0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with poly-cystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (p<0.01) and LH (p<0.05) plasma levels higher than control group and the highest free androgen index (FAI) values (13±0.87). All patients with irregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4±709 vs 5447±431 μIU/ml × 180min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809±432 ng/ml × 120min) in respect to controls (1708±208 ng/ml × 120min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618±119 ng/ml × 120min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

Effects of oral glucose administration on plasma growth hormone levels in women with polycystic ovary syndrome

OBJECTIVE To evaluate the sensitivity of GH secretion to the suppressive effect of oral glucose administration in women with polycystic ovary syndrome (PCOS). DESIGN Comparison of the GH response to an oral glucose load in women with PCOS and in weight-matched normally menstruating women (controls). SETTING Reproductive endocrinology unit. PATIENT(S) Eighteen obese and 11 nonobese patients and 10 obese and 10 nonobese controls. INTERVENTION(S) After an overnight fast, each woman underwent a 75-g, 3-hour oral glucose tolerance test (OGTT). MEAN OUTCOME MEASURE(S) Growth hormone, glucose, and insulin responses to OGTT. RESULT(S) No significant differences in the glycemic and insulinemic responses were found between the patients and the weight-matched controls. No decrease in plasma GH was observed in both obese and nonobese patients and in obese controls during the OGTT, whereas a significant GH decrease occurred in nonobese controls 60 and 120 minutes after glucose intake. CONCLUSION(S) Oral glucose administration was unable to suppress GH levels in nonobese as well as in obese women with PCOS and in obese control women. These data suggest that both PCOS and obesity are associated with a reduced sensitivity of GH secretion to glucose suppression.

CYP21A2 genetics: When genotype does not fit phenotype

• To increase awareness of genotype–phenotype correlation in congenital adrenal hyperplasia

Hashimoto's thyroiditis: an accidental discovery of a lingual thyroid in a 7-year-old child

An ectopic thyroid located at the base of the tongue is a rare entity, resulting from early developmental defects of thyroid gland embryogenesis during its descent from the foramen caecum to its normal eutopic pretracheal site. This condition is the main cause of congenital primary hypothyroidism, even though signs and symptoms of thyroid dysfunction may also appear later in childhood. Lingual thyroid may sometimes present with symptoms of respiratory obstruction or feeding difficulties. We illustrate the case of a 7-year-old girl with subclinical hypothyroidism due to Hashimoto’s thyroiditis arising in a lingual thyroid. She had never suffered from upper airway obstructive symptoms, but did refer a 3-month history of cough. Rapid normalisation of thyroid-stimulating hormone levels and termination of the cough were attained when the L-thyroxine treatment started. After 6 months a significant reduction of lingual thyroid size was also noted. The diagnostic procedures and therapeutic options in childhood are discussed.

Incidental Finding of Idiopathic Unilateral Adrenal Calcification in an 18-Month-Old Child: Case Report and Review of the Literature

ABSTRACT The presence of calcified lesions in the adrenal gland requires a careful endocrine, microbiological and radiological evaluation combined with detailed clinical history to confirm its non-evolving nature and avoid unnecessary surgery. We report an 18-month-old male child hospitalized with an incidentally discovered calcification in his right adrenal gland. All biochemical data as well as liver, renal and adrenal function tests were normal. Abdominal computed tomography scan showed that the right adrenal gland was completely occupied by a large calcification, which was put in relationship with an undetected adrenal distress during the neonatal period, as macrosomy and clavicle fracture of the newborn could let us suggest. Our report describes the diagnostic approach to disclose the nature of a suprarenal mass, which is particularly problematic when this is found incidentally. In addition, an extensive review of the medical literature dealing with non-traumatic adrenal calcifications and haemorrhages in children has been carried out.