Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy.

CONTEXT: Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland. OBJECTIVE: To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice. DESIGN: Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model. RESULTS: We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range. CONCLUSIONS: Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.

Expanded clinical spectrum in hepatocyte nuclear factor 1b-maturity-onset diabetes of the young.

AIMS: HNF1B-maturity-onset diabetes of the young is caused by abnormalities in the HNF1B gene encoding the transcription factor HNF-1beta. We aimed to investigate detailed clinical features and the type of HNF1B gene anomaly in five pediatric cases with HNF1B-MODY. METHODS: From a cohort of 995 children and adolescents with diabetes, we analyzed the most frequent maturity-onset diabetes of the young genes (GCK, HNF1A, HNF4A) including HNF1B sequencing and deletion analysis by quantitative Multiplex-PCR of Short Fluorescent Fragments (QMPSF) if patients were islet autoantibody-negative and had one parent with diabetes or associated extrapancreatic features or detectable C-peptide outside honeymoon phase. Presence and size of disease-causing chromosomal rearrangements detected by QMPSF were further analyzed by array comparative genomic hybridization. RESULTS: Overall, five patients had a heterozygous HNF1B deletion, presenting renal disease, elevated liver enzymes, and diabetes. Diabetes was characterized by insulin resistance and adolescent onset of hyperglycemia. Additionally, clinical features in some patients were pancreas dysplasia and exocrine insufficiency (two of five patients), genital defects (three of five), mental retardation (two of five), and eye abnormalities (coloboma, cataract in two of five). One case also had severe growth deficit combined with congenital cholestasis, and another case had common variable immune deficiency. All patients reported here had monoallelic loss of the entire HNF1B gene. Whole genome array comparative genomic hybridization confirmed a precurrent genomic deletion of approximately 1.3-1.7 Mb in size. CONCLUSION: The clinical data of our cases enlarge the wide spectrum of patients with HNF1B anomaly. The underlying molecular defect in all cases was a 1.3- to 1.7-Mb deletion, and paired, segmental duplications along with breakpoints were most likely involved in this recurrent chromosomal microdeletion.

Xanthogranulomatous pyelonephritis in children: diagnostic and therapeutic aspects.

Xanthogranulomatous pyelonephritis (XGP) is a rare, chronic inflammatory disease of the kidneys. It is characterized by destruction of renal parenchyma and accumulation of lipid-laden foamy macrophages. Diffuse and focal forms are known. The condition is mainly observed in middle-aged women, and it is very rare in childhood. Of 32 nephrectomies carried out in children for various diseases in our hospital over the course of 2 years, there were two cases of diffuse XGP. In both cases, the preoperative diagnosis based on ultrasound findings was highly suggestive of XGP. We present the two cases and define the typical ultrasonographic signs for distinguishing XGP from other renal masses. The diagnostic and therapeutic management is discussed and an overview of the literature is given.

Spontaneous regression of a vascular tumor of the skull base--infantile hemangioendothelioma?

Extracerebral masses involving the skull base in children and adolescents are rare. We report on a 4-month-old infant who was diagnosed with a large extracerebral mass in the anterior fossa. Subtotal resection to prevent impending blindness was complicated by almost fatal bleeding. Histopathologically, vessel malformation, epitheloid hemangioendothelioma, and angiosarcoma were possible diagnoses. The residual tumor regressed spontaneously and completely within 6 months after surgery. Retrospectively, histologic and radiologic findings and clinical course prompted the diagnosis of an infantile hemangioendothelioma. To our knowledge, this is the first report on an infantile hemangioendothelioma of the skull base.

Calvarial dermoids and epidermoids in infants and children: sonographic spectrum and follow-up.

OBJECTIVE: Dermoids and epidermoids are defined as ectodermal inclusion cysts. The aim of this study was to evaluate the spontaneous natural behavior and the ultrasonographic appearance of calvarial dermoids and epidermoids. MATERIALS AND METHODS: The ultrasonographic image datasets of 100 consecutive children up to 4 years of age (52 females, 48 males; age range at first examination 1 week to 40 months, mean age 8.3 +/- 6.9 months) presenting with a firm palpable calvarial mass (103 lesions) were studied retrospectively. All ultrasound (US) examinations were performed using a 7- to 10-MHz linear transducer including B-mode and color Doppler sonography. US follow-up studies (up to 47 months) could be achieved in 30 patients with 33 lesions. RESULTS: At first presentation, all 103 lesions demonstrated very similar US features: a round or oval configuration (diameter 3-18 mm), hypoechogenic, and homogeneous internal structures with a marked hyperechogenic superficial capsule, which were localized adjacent to or expanded into the osseous external calvarial table. No conspicuous flow signs on color Doppler were seen. In 33 lesions with US follow-up investigations, 49% showed variable signs of regression: reduction of size, increase of internal echogenicity, and decrease of demarcation. Eight lesions (24%) remained unchanged. A slight progression up to a maximum diameter of 17 mm but without any increase in osseous destruction was observed in the remainder (27%). There was no lesion with a complete destruction of the underlying bone and no intracranial extension in any of the cases. CONCLUSIONS: Calvarial dermoids and epidermoids in infants and children show a benign natural behavior with spontaneous regression in a large number of cases. On US, they demonstrate uniform pathognomonic features enabling the correct diagnosis in any of those lesions. Thus, additional, mainly radiation burdening and sometimes misleading imaging techniques should be restricted. Surgical treatment protocols should be handled conservatively and lesions should be primarily followed-up clinically and by US.

Early treatment with L-thyroxine in children and adolescents with type 1 diabetes, positive thyroid antibodies, and thyroid gland enlargement.

AIM: To investigate whether early treatment with l-thyroxine may prevent deterioration of thyromegaly and progression to subclinical or clinical hypothyroidism in pediatric patients with type 1 diabetes, positive thyroid antibodies, and ultrasound abnormalities of the thyroid gland. METHODS: The development of thyroid gland volume and function in patients without L-thyroxine treatment (group A, n = 8) was assessed and compared with that in patients receiving L-thyroxine treatment (group B, n = 7) with median follow-up time of 2.0 yr (range 0.6-3.0 yr). Standard deviation score (SDS) of thyroid gland volume was calculated according to gender- and age-corresponding data. RESULTS: Median thyroid gland volume SDS at study entry was 4.8 (range 2.0-15.3) in group A and 5.6 (3.6-13.9) in group B. At follow-up, median thyroid volume SDS has increased by 0.8 (-3.9 to 6.0) at 1 yr and by 2.0 (-4.5 to 10.9) at 2 yr in group A but decreased significantly by -3.4 (-10.0 to 0.4) and -5.3 (-12.3 to -1.7) in group B, respectively. The change of thyroid gland volume was significantly different between the two groups (p = .043 and .032, respectively). In group A, three of eight patients without therapy developed subclinical hypothyroidism with thyroid-stimulating hormone elevation. CONCLUSION: These data demonstrate that treatment with L-thyroxine in patients with diabetes, positive thyroid antibodies, and elevated gland volume leads to a significant reduction of thyromegaly. Prospective randomized clinical trials are required to prove these preliminary findings.

Uncommon synovial cysts in children.

UNLABELLED: Popliteal synovial cysts (Baker's cysts) are a common occurrence in children and adults. Synovial cysts in other locations and/or with atypical extension are less common and may be confounded with tumors or other medical conditions. In this article we describe the underlying disease, clinical presentation and clinical course in six children with a sudden onset of paraarticular soft tissue masses or non-specific chronic pain. Ultrasound was the initial imaging method used in all cases; this was supplemented by MRI in three patients. Four children were diagnosed to be suffering from juvenile idiopathic arthritis (JIA), one child from Lyme Arthritis, whereas in one child no underlying disease was identified. Well-demarcated hypoechogenic lesions without signs of perfusion extending from the shoulder (two patients), elbow (one patient), hip (one patient), knee (1) or ankle (one patient) far into the adjacent musculature were detected on ultrasonography. A direct connection to the joint was demonstrated in all cases. All synovial cysts in the five arthritic patients resolved rapidly with medical treatment for arthritis, whereas the cyst persisted in the non-JIA patient. CONCLUSION: Uncommon synovial cysts occur in particular as a complication of arthritis. Ultrasonography is the initial and follow-up imaging method of choice, which can be supplemented by MRI in unusual cases. Apart from treatment for arthritis, no specific therapeutic interventions were required in the present cases.

Transcranial Doppler ultrasonography in neurologically asymptomatic children and young adults with sickle cell disease.

The purpose of the study was to evaluate transcranial Doppler ultrasonography for identifying cerebrovascular disease in neurologically asymptomatic children and young adults with sickle cell disease. A total of 47 consecutive patients with sickle cell disease (28 females, 19 males; age range 8 months to 29 years, mean age 9 years 6 months) were evaluated by transcranial color and duplex Doppler ultrasonography via transtemporal and occipital (2-MHz probe) as well as by transocular (5-MHz probe) approach. Eleven vessels (middle, posterior, anterior cerebral artery, vertebral artery, ophthalmic artery on each side and basilar artery) were analyzed in each patient. Following nine transcranial Doppler findings predictive for cerebrovascular disease, patients with one or more of those abnormal sonographic findings underwent MR imaging and MR angiography. In 8 patients with abnormal transcranial Doppler the MR angiography was normal. Thirty-one patients demonstrated normal results. In 15 of 16 patients with one or more abnormal Doppler findings (34% of all studied patients) MR imaging and MR angiography were performed. The MR angiography disclosed cerebrovascular stenosis in 7 patients (15% of all patients, 44% of those with pathological transcranial Doppler findings). In one of those patients MR imaging revealed silent peripheral ischemic infarction as well. Our findings indicate the usefulness of transcranial Doppler ultrasonography to reveal occult cerebrovascular lesions in neurologically asymptomatic patients with sickle cell disease. It should regularly be performed in all sickle cell patients in order to detect patients at risk for later stroke. Patients with homozygous disease and a high frequency of preceding sickle cell crises should be followed most closely.

Unusual mesoblastic nephroma in a young child.

We report a 1-year 11-month-old girl demonstrating a large renal mass with a unique presentation on imaging (US, CT and plain radiography), pathology and histology. The imaging features did not correspond with a Wilms' tumour, the most commonly found renal tumour in the child of this age. The US and CT findings resembled a benign lesion with an unusually high fat content. Histological evaluation demonstrated a congenital mesoblastic nephroma, a tumour entity typical for the neonatal period or early infancy, with an additional unusual, predominantly lipomatous differentiation.

Testicular microlithiasis in children: sonographic features and clinical implications.

BACKGROUND: The natural history of incidentally discovered testicular microlithiasis in children has not been well defined. Although a benign condition, this entity has been found to be associated with testicular malignancies. OBJECTIVE: To determine the spectrum of sonographic findings and clinical implications in children with testicular microlithiasis. MATERIALS AND METHODS: During a 3.5-year period, 850 scrotal examinations with grey-scale US detected testicular microlithiasis in 16 boys (1.9%), age range 6-18 years. The US records of these patients were retrospectively analysed for distribution and pattern of this finding. The presence of intratesticular pathology was determined and the medical records and pathological reports were reviewed. In five patients, US re-evaluation up to 6 years could be performed. RESULTS: Typical punctate hyperechoic foci were found bilaterally in all cases except five, which showed only unilateral foci. Additional pathology was depicted in four patients (chorioncarcinoma n=1; a cystic lesion in a patient with a large-cell calcifying Sertoli-cell tumour, n=1; diffuse structural alterations after orchidopexy, n=2). No testicular tumour developed during clinical follow-up. CONCLUSIONS: The association with benign and malignant testicular tumours, as described in adults, also seems valid in the paediatric age group. Therefore, children with testicular microlithiasis should have clinical and US long-term follow-up.