Necrobiosis Lipoidica Diabeticorum: A pediatric case report.

INTRODUCTION: Necrobiosis lipoidica (NL) is a rare chronic granulomatous dermatitis that usually appears in the lower extremities. It affects about 0.3-1.2% of diabetic patients, the majority of whom have type 1 diabetes. The etiology and pathogenesis of this disorder are still unclear. NL is characterized by skin rash that usually affects the shins. The average onset is 30 years, with females being affected more commonly. There are very few reported cases of necrobiosis lipoidica in children. CASE REPORT: We report a case of a 16 year old girl affected by type 1 diabetes mellitus (15 years disease duration) who developed an erythematous nodular rash on the lower extremities and interscapular area. In the suspect of necrobiosis lipoidica, a skin biopsy was performed (lower extremities and interscapular area). The microscopic evaluation of the pretibial lesions was suggestive of necrobiosis lipoidica. The smaller lesions in the interscapular area showed signs of perivascular dermatitis which could be consistent with early stages of necrobiosis lipoidica. Local treatment with tacrolimus determined a progressive improvement of the lesions. CONCLUSION: In patients with T1DM, diagnosis of NL of the lower legs is usually unequivocal. However, diagnosis may be more challenging in the presence of lesions with recent onset and/or atypical clinical presentation and unusual site. In these cases, NL must always be taken in consideration in order to avoid misdiagnosis, wrong/late treatment decisions and progression to ulceration.

Sexual function in adult life following Passerini-Glazel feminizing genitoplasty in patients with congenital adrenal hyperplasia.

PURPOSE: We assessed external genitalia sensitivity and sexual function in adults with congenital adrenal hyperplasia who had undergone Passerini-Glazel feminizing genitoplasty as children, and compared them to a control group of healthy counterparts. MATERIALS AND METHODS: Inclusion criteria were congenital adrenal hyperplasia, Passerini-Glazel feminizing genitoplasty, adult age and penetrative vaginal intercourse. Thermal and vibratory sensitivity of the clitoris, vagina and labia minora were analyzed using the Genito Sensory Analyzer (Medoc Ltd., Minnetonka, Minnesota). Psychosexual outcome was assessed with the Beck Depression Inventory, Zung Self-Rating Anxiety Scale, Female Sexual Distress Scale and Female Sexual Function Index. Matched analyses were performed to compare outcomes in patients to controls (healthy medical students). All statistical tests were performed using SPSS®, version 18.0 RESULTS: A total of 12 patients (10%) entered the study. Thermal and vibratory clitoral sensitivity was significantly decreased in all patients compared to healthy controls (p <0.01). There was no difference in thermal or vibratory vaginal sensitivity between patients and controls. On the Female Sexual Distress Scale 11 patients (91.6%) and 11 controls (91.6%) described a stable satisfactory relationship. All patients reported active sexual desire, good arousal, adequate lubrication and orgasm. No significant difference in Female Sexual Function Index global score or single domain scores was observed between patients and controls. CONCLUSIONS: Although clitoral sensitivity in sexually active patients with congenital adrenal hyperplasia treated with Passerini-Glazel feminizing genitoplasty is significantly reduced compared to controls, sexual function in those patients is not statistically or clinically significantly different from their healthy counterparts. Finally, 1-stage Passerini-Glazel feminizing genitoplasty seems to allow normal adult sexual function.

Growth hormone therapy and respiratory disorders: long-term follow-up in PWS children.

CONTEXT: Adenotonsillar tissue hypertrophy and obstructive sleep apnea have been reported during short-term GH treatment in children with Prader-Willi syndrome (PWS). OBJECTIVE: We conducted an observational study to evaluate the effects of long-term GH therapy on sleep-disordered breathing and adenotonsillar hypertrophy in children with PWS. DESIGN: This was a longitudinal observational study. PATIENTS AND METHODS: We evaluated 75 children with genetically confirmed PWS, of whom 50 fulfilled the criteria and were admitted to our study. The patients were evaluated before treatment (t0), after 6 weeks (t1), after 6 months (t2), after 12 months (t3), and yearly (t4-t6) thereafter, for up to 4 years of GH therapy. The central apnea index, obstructive apnea hypopnea index (OAHI), respiratory disturbance index, and minimal blood oxygen saturation were evaluated overnight using polysomnography. We evaluated the adenotonsillar size using a flexible fiberoptic endoscope. RESULTS: The percentage of patients with an OAHI of >1 increased from 3 to 22, 36, and 38 at t1, t4, and t6, respectively (χ(2) = 12.2; P < .05). We observed a decrease in the respiratory disturbance index from 1.4 (t0) to 0.8 (t3) (P < .05) and the central apnea index from 1.2 (t0) to 0.1 (t4) (P < .0001). We had to temporarily suspend treatment for 3 patients at t1, t4, and t5 because of severe obstructive sleep apnea. The percentage of patients with severe adenotonsillar hypertrophy was significantly higher at t4 and t5 than at t0. The OAHI directly correlated with the adenoid size (adjusted for age) (P < .01) but not with the tonsil size and IGF-1 levels. CONCLUSION: Long-term GH treatment in patients with PWS is safe; however, we recommend annual polysomnography and adenotonsillar evaluation.

Rare cases of autoimmune hypothyroidism in young children.

Acquired autoimmune hypothyroidism is common in late childhood and adolescence but is very rare in the first 3 years of life. We report on three cases of autoimmune thyroiditis (AT) in young children who presented with constipation, decreased appetite, and increased hours of sleep. Our cases highlight that AT may remain undiagnosed for a long time in young children owing to the rarity of the disease.

Congenital hypothyroidism with eutopic thyroid gland: analysis of clinical and biochemical features at diagnosis and after re-evaluation.

CONTEXT: In recent years changes in screening strategies for congenital hypothyroidism (CH) led to an increased detection of mild forms of CH, associated with eutopic thyroid gland. OBJECTIVES: We aimed to determine the clinical evolution of CH with eutopic thyroid gland and to find out prognostic factors at diagnosis and follow-up. PATIENTS AND METHODS: We retrospectively analyzed a group of 84 children with CH and eutopic thyroid gland treated at our institution. They all underwent clinical re-evaluation after the age of 3, based on thyroid function testing after l-thyroxine therapy withdrawal, thyroid ultrasonography, and (123)I scintigraphy with perchlorate discharge test. Genetic analysis was performed in selected cases. RESULTS: At re-evaluation, 34.5% of patients showed permanent hypothyroidism and needed l-thyroxine reintroduction, 27.4% had persistent hyperthyrotropinemia (TSH 5-10 mU/L), and 38.1% had transient hypothyroidism. Major risk factors for permanent CH were prematurity, first-degree familial history of goiter/nodules, thyroid hypoplasia at diagnosis, and high l-thyroxine requirements at follow-up. Iodine organification defects were found in 29.7% of patients, 30% of whom harbored DUOX2 mutations. TSH receptor gene mutations were found in 8.7% of patients with persistent thyroid dysfunction and negative perchlorate discharge test. CONCLUSIONS: Only one-third of patients with CH and eutopic thyroid gland needed to continue l-thyroxine therapy after re-evaluation. A frequent finding was the persistence of mild hyperthyrotropinemia. The evolution of CH remains difficult to predict, although different clinical features might suggest different outcomes. Mutations in the genes commonly linked to mild forms of CH were documented in a minority of cases.

Central adrenal insufficiency in young adults with Prader-Willi syndrome.

OBJECTIVE: A high prevalence (60%) of central adrenal insufficiency (CAI) has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. We have assessed CAI in adults with PWS using the low-dose short synacthen test (LDSST). DESIGN: Basal cortisol and ACTH, and 30-min cortisol after the administration of 1 µg synacthen, were determined in 53 PWS adults (33 females). A peak cortisol value of ≥500 nmol/l was taken as normal. Hormonal profiles were analysed in relation to gender, genotype and phenotype. Deficient patients were retested by high-dose short synachten test (HDSST) or a repeat LDSST. RESULTS: Mean ± SD basal cortisol and ACTH were 336·6 ± 140·7 nmol/l and 4·4 ± 3·7 pmol/l respectively. Cortisol rose to 615·4 ± 135·0 nmol/l after LDSST. Eight (15·1%) patients had a peak cortisol response <500 nmol/l, with a lower mean ± SD (range) basal cortisol of 184·9 ± 32·0 (138·0-231·7) compared with 364·1 ± 136·6 (149·0-744·5) in normal responders (P < 0·001). Seven of the eight patients underwent retesting, with 4 (7·5%) showing persistent suboptimal responses. Basal and peak cortisol correlated in females (r = 0·781, P < 0·001). Logistic regression revealed that only female gender and baseline cortisol were predictors of cortisol peaks (adjusted R square 0·505). CONCLUSIONS: Although CAI can be part of the adult PWS phenotype, it has a lower prevalence (7·5%) than previously reported. Clinicians are advised to test PWS patient for CAI. Our study also shows that basal cortisol is closely correlated with adrenal response to stimulation, indicating that its measurement may be helpful in selecting patients for LDSST.

Future Perspectives in Glucose Monitoring Sensors.

The prevalence of diabetes is increasing. improved glucose control is fundamental to reduce both long-term micro- and macrovascular complications and short-term complications, such as diabetic ketoacidosis and severe hypoglycemia. Frequent blood glucose monitoring is an essential part of diabetes management. However, almost all available blood glucose monitoring devices are invasive. This determines a reduced patient compliance, which in turn reflects negatively on glucose control. Therefore, there is a need to develop noninvasive glucose monitoring devices that will reduce the need of invasive procedures, thus increasing patient compliance and consequently improving quality of life and health of patients with diabetes.

Asymptomatic thyrotropin-secreting pituitary macroadenoma in a 13-year-old girl: successful first-line treatment with somatostatin analogs.

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSHomas) are an extremely rare cause of hyperthyroidism. Up to now there are only few cases reported in the pediatric age range. Thefirst therapeutic option is surgical resection, whereas medical treatment with somatostatin analogs has been reported only in cases wherein surgery was unsuccessful. PATIENT FINDINGS: A 13-year-old girl was referred to our clinic for incidental finding of increased circulating free thyroid hormones in the presence of detectable TSH concentrations. She had no signs/symptoms of thyrotoxicosis. Resistance to thyroid hormone was excluded due to the lack of TSH response after thyrotropin-releasing hormone (TRH) stimulation test. Cerebral magnetic resonance imaging showed the presence of a large pituitary macroadenoma, with intra- and suprasellar extension. We decided to treat this patient with somatostatin analog as a first-line therapy because of high surgery risks due to the tumor dimensions. The response to medical treatment was excellent, with rapid and significant tumor shrinkage. No major side effects were reported. The patient developed central hypothyroidism that was corrected with L-thyroxine therapy. SUMMARY: We report the first pediatric case of TSHoma treated with somatostatin analog as a first-line therapy. The diagnosis was challenging because of the insidious and asymptomatic presentation of the tumor. CONCLUSIONS: We conclude that somatostatin analogs should be considered as first choice, bridge-to-surgery treatment in young patients, in order to reduce neurosurgical complications and prevent hypopituitarism during pubertal development.

Sensor-augmented pump therapy in very young children with type 1 diabetes: an efficacy and feasibility observational study.

BACKGROUND: Efficacy and feasibility of sensor-augmented pump (SAP) therapy were evaluated in very young children with type 1 diabetes (T1D). SUBJECTS AND METHODS: SAP (Dexcom [San Diego, CA] Seven Plus™ usage combined with insulin pump) therapy was retrospectively evaluated in 28 children (15 boys) younger than 7 years (mean age, 5.8 ± 1.2 years; range, 3-7 years), with T1D. Glycosylated hemoglobin (HbA1c) was evaluated at baseline and at the end of the study, as were efficacy and feasibility of the system, using a rating scale (with 3 being the most positive). RESULTS: SAP has been used for at least 6 months by 85% of patients, with an overall good satisfaction (92%). The greatest perceived benefit was the reduced fear of hypoglycemia (score of 3, 81%). HbA1c significantly improved only in patients with baseline HbA1c >7.5% (P = 0.026). CONCLUSIONS: SAP therapy is effective and feasible in preschool children with T1D. In patients with high HbA1c at baseline it provide a 0.9% decrease, sustained for at least 6 months.

46,XY karyotype in a female phenotype fetus: a challenging diagnosis.

BACKGROUND: The growing use of prenatal investigations allows an early detection of several inborn disorders, including disorders of sexual development. The management of these conditions is an arising problem. CASE: 46,XY karyotype and female phenotype were detected in a fetus; 5α-reductase and androgen receptor gene analysis on chorionic villi revealed no relevant mutation. The newborn was assigned to female sex. The diagnosis of 17ß-hydroxysteroid dehydrogenase-3 ß-OL deficiency was reached at four months of age, by means of a low testosterone/Δ 4-androstenedione ratio after HCG test and HSD17B3 gene analysis. SUMMARY AND CONCLUSION: A 46,XY fetus with female external genitalia suggests different conditions, some very rare. Specific genetic investigations should be performed prenatally when possible. A complete evaluation is mandatory after delivery to reach a correct diagnosis.

Surgical management of pediatric Graves' disease: an effective definitive treatment.

PURPOSE: The optimal treatment for pediatric Graves' disease (GD) is controversial. Antithyroid drugs are often used initially, but they are associated with a high failure rate. Therefore alternative therapies have become important. In the present study, we analyze our institution's experience regarding the safety and efficacy of thyroid surgery among pediatric patients with GD. METHODS: This is a retrospective chart review of 27 pediatric patients (age ≤ 18 years) with GD who underwent thyroid surgery between 1991 and 2009 at a single academic Institution. We recorded preoperative, intraoperative, and short-term postoperative data. RESULTS: All 27 patients were initially treated with thionamides. The high rate of hyperthyroidism relapse after discontinuation of medical treatment, age < 5 years, adverse reaction to medical therapy, severe ophthalmopathy, and patient preference justified the final decision to proceed with surgery as definitive therapy. All patients underwent total thyroidectomy. We had no mortality; surgical complications were rare: 4 (14.8 %) cases of transient hypocalcemia, 1 (3.7 %) of permanent hypocalcemia, 3 (11.1 %) of transient RLN neuropraxia, and 2 (7 %) of keloid scar. No bleeding, permanent RLN palsy or relapse hyperthyroidism were reported. CONCLUSIONS: Surgical therapy for pediatric GD performed by experienced thyroid surgeons is a safe, definitive and cost-effective treatment.

Difficult treatment of consumptive hypothyroidism in a child with massive parotid hemangioma.

Consumptive hypothyroidism is a rare condition related to massive infantile hemangiomas producing an excess of the thyroid-hormone-inactivating enzyme type 3 iodothyronine deiodinase. We report the first case of consumptive hypothyroidism secondary to a large parotid hemangioma, highlighting the difficulties in selecting an adequate therapeutic strategy. The affected child was initially referred to our center for congenital hypothyroidism with a hypoplastic thyroid gland. L-Thyroxine (L-T4) replacement therapy was started at seven days of life. In the following weeks, the hemangioma rapidly increased in volume and the child developed severe hypothyroidism refractory to high doses of L-T4 therapy. The concentration of reverse triiodothyronine was elevated, suggesting that the underlying cause was an excessive conversion of thyroid hormones by high type 3 iodothyronine deiodinase levels in the tumor. Corticosteroid treatment showed only partial benefit. Introduction of propranolol instead led to normalization of thyroid hormones along with a dramatic involution of the hemangioma.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome.

OBJECTIVE: A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader-Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low-Dose Tetracosactrin Stimulation Test (LDTST), 1 µg] or standard-dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. DESIGN: Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre. PATIENTS: Eighty-four children with PWS. MEASUREMENTS: Assessment of adrenal response by morning cortisol and ACTH dosage, and 1-µg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm; below this threshold, patients were submitted to a second test. Responses were correlated with the patients' clinical and molecular characteristics to assess genotype-phenotype correlation. RESULTS: Pathological cortisol peak responses to the LDTST were registered in 12 patients (14.3%) who had reduced basal (169.4 ± 83.3 nm) and stimulated (428.1 ± 69.6 nm) cortisol levels compared to patients with normal responses (367.1 ± 170.6 and 775.9 ± 191.3 nm, P < 0.001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0.001), and the patients' ages (P < 0.001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0.030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r(2) = 0.353, P < 0.001). Standard-dose (250 µg) tetracosactrin test confirmed CAI in 4/12 patients (4.8% of the cohort). CONCLUSIONS: Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood.

Vitamin D dependent rickets, diagnostic and therapeutic difficulties: two case reports.

There are two types of vitamin D dependent rickets (VDDR) that cause rickets in children. Vitamin D dependent rickets type 1 (VDDR-I) is caused by an inborn error of vitamin D metabolism, which interferes with renal conversion of calcidiol (25OHD) to calcitriol (1,25(OH)2D) by the enzyme 1alpha-hydroxylase. Vitamin D dependent rickets type 2 (VDDR-II) is caused by a defect in the vitamin D receptor (VDR). We report cases of two African children affected by VDDR-I and VDDR-II, respectively. Establishing an early diagnosis of these genetic forms of rickets is challenging, especially in developing countries where nutritional rickets (NR) is the most common variety of the disease. A prompt diagnosis is necessary to initiate adequate treatment, resolve biochemical features and prevent complications, such as severe deformities that may require surgical intervention.

Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series.

OBJECT: Craniopharyngioma accounts for 2%-5% of all primary intracranial neoplasms. The optimal management of craniopharyngioma remains controversial. The authors evaluated the early results of surgery and the longterm risk of tumor recurrence in a large series of patients undergoing resection of craniopharyngiomas. METHODS: Between 1990 and 2008, 112 consecutive patients (57 male and 55 female patients with a mean [± SEM] age of 33.3 ± 1.8 years) underwent resection of craniopharyngiomas at the authors' hospital. Recurrence or growth of residual tumor tissue during follow-up was assessed using MR imaging. RESULTS: There were 3 perioperative deaths (2.7%). Severe adverse events were more frequent in patients who underwent operations via the transcranial route (37%) than the transsphenoidal approach (5.6%; p < 0.001). Magnetic resonance imaging showed radical resection of the tumor in 78 (71.6%) of the remaining 109 patients. Previous surgery and maximum tumor diameter were associated with persistence of disease after surgery. Craniopharyngioma recurred in 26 (24.5%) of 106 patients. Presence of residual tumor on the first postoperative MR imaging, male sex, and no postoperative radiation therapy were associated with a risk of tumor recurrence. Quality-of-life data were assessed in the 91 patients who attended the authors' institution for follow-up visits. Among them, 8.8% patients were partially or completely dependent on others for daily living activities before surgery. This percentage increased to 14.3% at the last follow-up visit. The 5- and 10-year overall survival rates were 94.4% (95% CI 90.0%-98.8%) and 90.3% (95% CI 83.4%-97.3%), respectively. CONCLUSIONS: Complete surgical removal of craniopharyngioma can be achieved with reasonable safety in more than 70% of patients. Recurrence of craniopharyngioma may occur even after apparent radical excision. Prompt management of residual or recurring disease by radiotherapy, repeat surgery, or a combination of both is usually successful in controlling further tumor growth.

Patients' evaluation of nocturnal hypoglycaemia with GlucoDay continuous glucose monitoring in paediatric patients.

A study was conducted to evaluate the accuracy of GlucoDay (A. Menarini Diagnostics) during 48 h of continuous glucose monitoring (CGMS) in type 1 diabetic adolescents and use this novel approach to assess otherwise ignored nocturnal hypoglycaemias, in relationship to intermediate-acting insulin administration timing. Twenty type 1 diabetic adolescents with poor metabolic control were selected from our out-patient department. Equal doses of intermediate insulin were administered at 19:00 and at 22:00 of the first and second night of the study, respectively. Correlation coefficient between GlucoDay and standard glucometer was 0.94; 98.3% of data fall in the A + B area of Error Grid Analysis and 1.7% in the D area. The mean error was 13.9% overall and 16.4% with blood glucose values (BGV) <75 mg/dl. The accuracy, ±15 mg/dl, was 82% for BGV <75 mg/dl and 74% for BGV >75 mg/dl. The CGMS discovered nocturnal hypoglycaemia (NH) in 12/18 patients, but no severe hypoglycaemia. During the first night, 8 asymptomatic NH episodes were found with BGV <60 mg/dl and 12 with BGV <80. During the second night, 4 asymptomatic NH episodes with BGV <60 mg/dl and 5 with BGV <80 were found. Furthermore, during the second night, the mean duration of BGV <126 mg/dl was lower than in the first night. GlucoDay is a reliable device for CGMS in paediatric patients and able to determine asymptomatic NH. Bedtime insulin injections provided safer glycaemic profiles and a lower percentage of hypoglycaemic events, representing a safer insulin administration scheme.

Newborn of mothers affected by autoimmune thyroiditis: the importance of thyroid function monitoring in the first months of life.

BACKGROUND: Evaluation of thyroid function in neonates born from mothers affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb) and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated. METHODS: 129 neonates were tested for thyroid function by measurement of free thyroxine (FT4) and thyroid stimulating hormone (TSH) in 3th day, 15th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected. RESULTS: 28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population. CONCLUSIONS: Transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mothers affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to carefully monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2nd and 4th week of life.

Pseudohypoparathyroidism, an often delayed diagnosis: a case series.

Pseudohypoparathyroidism refers to a heterogeneous group of disorders characterized by parathyroid hormone (PTH) resistance. Pseudohypoparathyroidism is an uncommon sporadic or inherited genetic disorder subdivided into several distinct entities (type Ia, Ib, Ic, type II). We report cases of four children (aged 8 to 13 years) in the winter season 2007-'08. The present work highlights the variable mode of presentation of pseudohypoparathyroidism and the difficulty of an early diagnosis. We stress the importance of a complete biochemical investigation of the calcium-phosphate metabolism to recognize typical biochemical alterations associated with this condition (hypocalcaemia, hyperphosphataemia with increased phosphate tubular reabsorption and elevated PTH levels) in spite of a phenotypic aspect that often lacks the presence of all the peculiar clinical features of Albright hereditary osteodistrophy.

A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH).

CONTEXT: The guidelines of the National Academy of Clinical Biochemistry advocated the use of low bloodspot TSH (b-TSH) threshold for newborn screening of congenital hypothyroidism (CH). The impact generated by the application of this indication is largely unknown. OBJECTIVE: To determine the impact on CH epidemiology and classification generated by the introduction of low b-TSH cutoff. DESIGN: Retrospective study of 629,042 newborns screened with b-TSH cutoffs of 12 (years 1999-2002) or 10 mU/l (2003-2005). MEASUREMENTS: Congenital hypothyroidism incidence and classification. Results were compared with those virtually obtained with the previous cutoff (20 mU/l). Clinical re-evaluation after L-T4 withdrawal of a representative group of 140 CH children at 3-5 years. RESULTS: Low b-TSH cutoffs allowed the detection of 435 newborns with confirmed CH (incidence 1:1446). Forty-five percent of CH infants, including 12/141 dysgenesis, would have been missed using the 20 mU/l cutoff. In contrast to current classification, 32% CH newborns had thyroid dysgenesis and 68% had a gland in situ (GIS). Premature birth was present in 20% of cases being associated with a 3-5 fold increased risk of GIS CH. Re-evaluation at 3-5 years showed a permanent thyroid dysfunction in 78% of 59 CH toddlers with GIS. CONCLUSIONS: The use of low b-TSH cutoff allowed the detection of an unsuspected number of children with neonatal hypothyroidism, evolving in mild permanent thyroid dysfunction later in life. The incidence of CH in this Italian population appears to be double than previously thought with a clear-cut prevalence of functional defects over dysgenetic ones.