Congenital hypothyroidism in a kitten resulting in decreased IGF-I concentration and abnormal liver function tests

A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully.

Lung-function tests in neonates and infants with chronic lung disease: tidal breathing and respiratory control

This paper is the fourth in a series of reviews that will summarize available data and critically discuss the potential role of lung-function testing in infants with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses information derived from tidal breathing measurements within the framework outlined in the introductory paper of this series, with particular reference to how these measurements inform on control of breathing. Infants with acute and chronic respiratory illness demonstrate differences in tidal breathing and its control that are of clinical consequence and can be measured objectively. The increased incidence of significant apnea in preterm infants and infants with chronic lung disease, together with the reportedly increased risk of sudden unexplained death within the latter group, suggests that control of breathing is affected by both maturation and disease. Clinical observations are supported by formal comparison of tidal breathing parameters and control of breathing indices in the research setting.

Expression of nitric oxide synthase III in human thyroid follicular cells: evidence for increased expression in hyperthyroidism

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.

Long-term follow-up after complete resection of well-differentiated cancer confined to the thyroid gland

BACKGROUND: Papillary or follicular thyroid carcinomas exhibit a relatively benign course. Hence, long-term follow-up studies with well-defined disease stages and treatment details are needed to evaluate treatment strategies. METHODS: Patients who underwent complete resection of well-differentiated thyroid carcinoma (WDTC) confined to the thyroid gland between 1972 and 1990 identified from a prospective database were assessed. Follow-up was performed by interview, review of patient charts, and analysis of the Death Registry. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). Review of histology was performed and extent of thyroid resection, postoperative therapy, and recognized prognostic factors but not lymphadenectomy were evaluated. RESULTS: Of 2,867 patients, 213 had complete resection of WDTC confined to the thyroid gland. Follow-up was completed in 166 patients with median age 54.2 (range, 20-85) years, and median follow-up of 27.2 (range, 15.6-34.5) years. The 10- and 20-year OS was 71 and 55%, respectively. DSS at 10 and 20 years was 81 and 69%, respectively, and correlated with age, histology, tumor size, radio-iodide ablation (RIA), and external beam irradiation (EBR) treatment. No patient died of WDTC more than 18 years after resection. Total or near-total thyroidectomy without lymphadenectomy was not superior to partial thyroidectomy. In multivariate analysis for DSS, age was the dominant factor, which correlated with histology. CONCLUSION: After a median follow-up of 27 years, about one-third of patients died of WDTC. Age, histology and postoperative therapy but not extent of thyroid resection determined DSS.

Steroid-responsive encephalopathy associated with Hashimoto thyroiditis

An 11-year-old girl presented with sudden sensory disturbance and left-sided muscle weakness. MRI revealed ischaemic change in the right lateral thalamus and the right internal capsule. During sonographic work-up of the cervical arteries, inflammation of the thyroid gland was noted. The results of the thyroid function tests and antibody titers confirmed Hashimoto thyroidits. Under high-dose corticosteroids, the girl had a full neurological recovery.

Morbidity rate of reoperation in thyroid surgery: a different point of view

Goitre recurrence is a common problem following subtotal thyroid gland resection for multinodular goitre disease. The aim of the present study was to evaluate morbidity rate in relation to the side of initial and redo-surgery for recurrent disease.

Consensus statement for inert gas washout measurement using multiple- and single- breath tests

Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

Extended resection for thyroid disease has less operative morbidity than limited resection

BACKGROUND: Theodor Kocher, surgeon and Nobel laureate, has influenced thyroid surgery all over the world: his treatment for multinodular goiter-subtotal thyroidectomy-has been the "Gold Standard" for more than a century. However, based on a new understanding of molecular growth mechanisms in goitrogenesis, we set out to evaluate if a more extended resection yields better results. METHODS: Four thousand three hundred and ninety-four thyroid gland operations with 5,785 "nerves at risk" were prospectively analyzed between 1972 and 2002. From 1972 to 1990, the limited Kocher resections were performed, and from 1991 to 2002 a more radical resection involving at least a hemithyroidectomy was performed. RESULTS: The incidence of postoperative nerve palsy was 3.6%; in the first study period and 0.9%; in the second (P < 0.001, Fisher's exact). Postoperative hypoparathyroidism decreased from 3.2%; in the first period to 0.64%; in the second (P < 0.01). The rate of reoperation for recurrent disease was 11.1%; from 1972 to 1990 and 8.5%; from 1991 to 2002 (P < 0.01). CONCLUSIONS: Extended resection for multinodular goiter not only significantly reduced morbidity, but also decreased the incidence of operations for recurrent disease. Our findings in a large cohort corroborate the suggestions that Kocher's approach should be replaced by a more radical resection, which actually was his original intention more than 130 years ago.

Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

BACKGROUND: To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. METHODS: Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. RESULTS: All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 - 39 days) and the median total RT dose was 40 Gy (range, 36 - 60 Gy). Median lacrimal gland exposure was 35.9 Gy (range, 16.8 - 42.6 Gy). Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. CONCLUSION: The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome.

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms.The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data.In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child.Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

Paediatric thyroid surgery is safe - experiences at a tertiary surgical centre.

PRINCIPLES Thyroidectomy in children is rare and mostly performed because of thyroid neoplasms. The aim of this study based on prospective data acquisition was to evaluate whether thyroid surgery in children can be performed as safely as in adults when undertaken by a team of adult endocrine surgeons and paediatric surgeons. METHODS Between 2002 and 2012, 36 patients younger than 18 years underwent surgery for thyroid gland pathologies. All surgical procedures were performed by an experienced endocrine surgeon and a paediatric surgeon. Baseline demographic data, surgical procedure, duration of operation, length of hospital stay, and postoperative morbidity and mortality were analysed. RESULTS The median age of all patients was 13 years (range 2-17 years), with predominantly female gender (n = 30, 83%). The majority of operations were performed because of benign thyroid disease (n = 27, 75%) and only a minority because of malignancy or genetic abnormality with predisposition for malignant transformation (MEN) (n = 9, 25%). Total thyroidectomy was performed in the majority of the patients (n = 24, 67%). The median duration of the surgical procedure was 153 minutes (range 90-310 minutes). The median hospital stay was 5 days (3-1 days). One patient developed persistent hypoparathyroidism after neck dissection due to cancer. One persistent and two temporary recurrent nerve palsies occurred. CONCLUSION This study demonstrated that paediatric thyroidectomy is safe as performed by this team of endocrine and paediatric surgeons, with acceptable morbidity even when total thyroidectomy was performed in the case of benign disease.

Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

Background Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. Results We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable. Conclusions We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.

[Non-alcoholic steatohepatitis - from NAFLD to MAFLD]

Non-alcoholic steatohepatitis (NASH) as one entity of non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and accompanies the rise in the prevalence of obesity, diabetes mellitus, hypertension and hyperlipidemia in the western world. It is not known why some patients progress in the disease and develop inflammation in the liver, whereas others remain in the stage of simple steatosis, which generally has a benign course. However, NASH can progress to fibrosis and cirrhosis as well as hepatocellular carcinoma. Therefore, it is important to determine the stage of the disease in patients presenting with the metabolic syndrome and abnormal liver function tests, suggesting NAFLD. Liver biopsy is the only tool that allows for reliable detection, grading and staging of liver disease. The main strategies in the treatment of NASH are correction of risk factors (lifestyle modifications, insuline sensitizer) and anti-oxidants (ursodeoxycholic acid, vitamin E) which both have been shown to improve liver histology as well as liver enzymes. Patients wih alcoholic fatty liver disease (AFLD) present the same liver histology and often also metabolic alterations similar to metabolic syndrome. Therefore, MAFLD (metabolic syndrome-associated fatty liver disease) might describe both patient populations more accurately and also describes the pathophysiological characteristics.

Tumor classification of six common cancer types based on proteomic profiling by MALDI imaging

In clinical diagnostics, it is of outmost importance to correctly identify the source of a metastatic tumor, especially if no apparent primary tumor is present. Tissue-based proteomics might allow correct tumor classification. As a result, we performed MALDI imaging to generate proteomic signatures for different tumors. These signatures were used to classify common cancer types. At first, a cohort comprised of tissue samples from six adenocarcinoma entities located at different organ sites (esophagus, breast, colon, liver, stomach, thyroid gland, n = 171) was classified using two algorithms for a training and test set. For the test set, Support Vector Machine and Random Forest yielded overall accuracies of 82.74 and 81.18%, respectively. Then, colon cancer liver metastasis samples (n = 19) were introduced into the classification. The liver metastasis samples could be discriminated with high accuracy from primary tumors of colon cancer and hepatocellular carcinoma. Additionally, colon cancer liver metastasis samples could be successfully classified by using colon cancer primary tumor samples for the training of the classifier. These findings demonstrate that MALDI imaging-derived proteomic classifiers can discriminate between different tumor types at different organ sites and in the same site.

Management of primary ciliary dyskinesia in European children: recommendations and clinical practice

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.