Operative Volume of Newborn Surgery in German University Hospitals: High Volume Versus Low Volume Centers.

INTRODUCTION: Adequate patient volume is essential for the maintenance of quality, meaningful research, and training of the next generation of pediatric surgeons. The role of university hospitals is to fulfill these tasks at the highest possible level. Due to decentralization of pediatric surgical care during the last decades, there is a trend toward reduction of operative caseloads. The aim of this study was to assess the operative volume of the most relevant congenital malformations at German academic pediatric surgical institutions over the past years. METHODS: Nineteen chairpersons representing university-chairs in pediatric surgery in Germany submitted data on 10 index procedures regarding congenital malformations or neonatal abdominal emergencies over a 3-year period (2015 through 2017). All institutions were categorized according to the total number of respective cases into "high," "medium," and "low" volume centers by terciles. Some operative numbers were verified using data from health insurance companies, when available. Finally, the ratio of cumulative case load versus prevalence of the particular malformation was calculated for the study period. RESULTS: From 2015 through 2017, a total 2,162 newborns underwent surgery for congenital malformations and neonatal abdominal emergencies at German academic medical centers, representing 51% of all expected newborn cases nationwide. The median of cases per center within the study period was 101 (range 18-258). Four institutions (21%) were classified as "high volume" centers, four (21%) as "medium volume" centers, and 11 (58%) as "low volume" centers. The proportion of patients operated on in high-volume centers varied per disease category: esophageal atresia/tracheoesophageal fistula: 40%, duodenal atresia: 40%, small and large bowel atresia: 39%, anorectal malformations: 40%, congenital diaphragmatic hernia: 56%, gastroschisis: 39%, omphalocele: 41%, Hirschsprung disease: 45%, posterior urethral valves: 39%, and necrotizing enterocolitis (NEC)/focal intestinal perforation (FIP)/gastric perforation (GP): 45%. CONCLUSION: This study provides a national benchmark for neonatal surgery performed in German university hospitals. The rarity of these cases highlights the difficulties for individual pediatric surgeons to gain adequate clinical and surgical experience and research capabilities. Therefore, a discussion on the centralization of care for these rare entities is necessary.

[Current Treatment of Oesophageal Atresia]. / Aktuelle Behandlungsstrategien der Ösophagusatresie.

Oesophageal atresia is a rare congenital malformation occurring in 1 : 3000/1 : 4000 neonates. Surgical correction is always required. Perioperative management concepts depend on the type of malformation. Postoperative results are closely related to postsurgical complications. Interdisciplinary management should extend from prenatal diagnosis, birth and perinatal care to neonatal intensive care and paediatric surgical therapy with specialised pediatric anaesthesia. Other areas that should be available are logopedia, paediatric gastroenterology and paediatric pulmonology. Long-term care should include systematic aftercare and transition programs to adult medicine.

Multidisciplinary long-term care and modern surgical treatment of congenital melanocytic nevi - recommendations by the CMN surgery network.

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, "Netzwerk Nävuschirurgie", NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi-stage procedure. Today, the long-term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of "removal at any cost" no longer holds. Potential treatment-related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus-based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.

Sonographic differentiation of complicated from uncomplicated appendicitis.

OBJECTIVE: This study aims to differentiate acute uncomplicated and complicated appendicitis, by investigating the correlation between sonographic findings and histological results in different types of paediatric appendicitis. METHODS: This is a retrospective study of 1017 paediatric patients (age < 18 years) who underwent ultrasound by paediatric radiologists before appendicectomy at our institution between 2006 and 2016. Histologically, uncomplicated appendicitis was primarily associated with transmural infiltration of neutrophil granulocytes, while complicated appendicitis was characterised by transmural myonecrosis. Logistic regression analyses were used to investigate the association between sonographic and histological findings. RESULTS: Out of 566 (56%) male and 451 (44%) female patients with a mean age of 10.7 years, uncomplicated appendicitis was histologically diagnosed in 446 (44%) children and complicated appendicitis was diagnosed in 348 (34%) cases. The following ultrasound findings were significantly associated with complicated appendicitis in multivariate regression: an increased appendiceal diameter (OR = 1.3, p < .001), periappendiceal fat inflammation (OR = 1.5, p = 0.02), the presence of an appendicolith (OR = 1.7, p = 0.01) and a suspected perforation (OR = 6.0, p < .001) by the pediatric radiologist. For complicated appendicitis, an appendiceal diameter of more than 6 mm had the highest sensitivity (98%), while a sonographically suspected perforation showed the highest specificity (94%). CONCLUSION: Abdominal sonography by paediatric radiologists can differentiate between uncomplicated and complicated appendicitis in paediatric patients by using an increased appendiceal diameter, periappendiceal fat inflammation, the presence of an appendicolith and a suspected perforation as discriminatory markers. ADVANCES IN KNOWLEDGE: This paper demonstrates expanded information on ultrasound, which is not only an essential tool for diagnosing appendicitis, but also a key method for distinguishing between different forms of appendicitis when performed by paediatric radiologists. Compared with previous studies, the crucial distinction features in our analysis are 1) the definition of gangrene and not primarily perforation as an acute complicated appendicitis enabling early decision-making by sonography and 2) a large number of patients in a particularly affected age group.

Correction to: Phlegmonous appendicitis in children is characterized by eosinophilia in white blood cell counts.

The original article can be found online.

Phlegmonous appendicitis in children is characterized by eosinophilia in white blood cell counts.

BACKGROUND: Phlegmonous and complicated appendicitis represent independent entities depending on hereditary immunological mechanisms. However, clinically there are no means to distinguish uncomplicated phlegmonous from complicated appendicitis. The ability to distinguish these two forms of appendicitis is relevant as current attempts are to treat both forms of the disease differently. The aim of the present study was to investigate differences in white blood cell counts (WBCs) in these conditions to identify areas of interest for future molecular studies. METHODS: White blood cell counts of patients aged between 7 and 14 years who underwent appendectomy from January 2008 to June 2016 were investigated with special reference to particular cellular subpopulations. RESULTS: A total of 647 children were included in the study. Within distinct inflammatory patterns, significant eosinophilia and basophilia were found in phlegmonous inflammation compared with complicated inflammation (0.11 ± 0.19 × 109/L vs. 0.046 ± 0.104 × 109/L, P < 0.0001, and 0.033 ± 0.031 × 109/L vs. 0.028 ± 0.024 × 109/L, P < 0.001). CONCLUSIONS: Compared with complicated disease, phlegmonous appendicitis seems to depend primarily on eosinophil inflammation. This observation is stable over time and indicates a direction for investigation of underlying genetic prerequisites.

Obstruction of peritoneal dialysis catheter is associated with catheter type and independent of omentectomy: A comparative data analysis from a transplant surgical and a pediatric surgical department.

BACKGROUND: Peritoneal dialysis (PD) catheter occlusion is a common complication with up to 36% of catheter obstructions described in the literature. We present a comparison of complications and outcome after implantation of PD catheters in a transplant surgical and a pediatric surgical department. METHODS: We retrospectively analyzed 154 PD catheters, which were implanted during 2009-2015 by transplant surgeons (TS, University Medical Center Hamburg-Eppendorf, Germany, n=85 catheters) and pediatric surgeons (PS, Charité University Medicine Berlin, Germany, n=69 catheters) in 122 children (median (range) age 3.0 (0.01-17.1) years) for acute (n=65) or chronic (n=89) renal failure. All catheters were one-cuffed or double-cuffed curled catheters, except that straight catheters were implanted into smaller children (n=19) by TS in Hamburg. RESULTS: Patient characteristics and operation technique did not differ between the departments. Peritonitis was the most common complication (33 catheters, 21.4%). Leakage (n=18 catheters, 11.7%) occurred more often in children weighing <10kg (p<0.001). The incidence of obstruction and dysfunction was significantly higher in catheters used in PS than catheters used in TS (30.4% vs. 11.8%, p=0.004). Omentectomy did not reduce the incidence of catheter obstruction (p=1.0). Perforation at the catheter tips was larger and appeared to be rougher in catheters used in PS than the catheters in TS. CONCLUSIONS: The type of catheter and presumably the type of perforation at the catheter tip may influence the incidence of peritoneal dialysis catheter obstruction.

Pulmonary outcome of esophageal atresia patients and its potential causes in early childhood.

INTRODUCTION: The aim of this study was to illustrate the pulmonary long term outcome of patients with repaired esophageal atresia and to further examine causes and correlations that might have led to this outcome. METHODS: Twenty-seven of 62 possible patients (43%) aged 5-20years, with repaired esophageal atresia were recruited. Body plethysmography and spirometry were performed to evaluate lung function, and the Bruce protocol treadmill exercise test to assess physical fitness. Results were correlated to conditions such as interpouch distance, gastroesophageal reflux or duration of post-operative mechanical ventilation. RESULTS: Seventeen participants (63%) showed abnormal lung function at rest or after exercise. Restrictive ventilatory defects (solely restrictive or combined) were found in 11 participants (41%), and obstructive ventilatory defects (solely obstructive or combined) in 13 subjects (48%). Twenty-two participants (81%) performed the Bruce protocol treadmill exercise test to standard. The treadmill exercise results were expressed in z-score and revealed to be significantly below the standard population mean (z-score=-1.40). Moreover, significant correlations between restrictive ventilatory defects and the interpouch distance; duration of post-operative ventilation; gastroesophageal reflux disease; plus recurrent aspiration pneumonia during infancy; were described. CONCLUSION: It was shown that esophageal atresia and associated early complications have significant impact on pulmonary long term outcomes such as abnormal lung function and, in particular restrictive ventilatory defects. Long-running and regular follow-ups of patients with congenital esophageal atresia are necessary in order to detect and react to the development and progression of associated complications such as ventilation disorders or gastroesophageal reflux disease. LEVEL OF EVIDENCE: Prognosis study, Level II.

Voiding Cystourethrography in the Diagnosis of Anorectal Malformations.

Introduction In a newborn with an anorectal malformation (ARM), it is vital to determine the anatomy of the underlying defect. After a colostomy has been created, distal colostography (DCG) is currently the chosen modality for the detection of fistulas. The role of voiding cystourethrography (VCU) is unexplored. Aim The aim of this study was to analyze the reproducibility of DCG and VCU in assessing the underlying malformation in ARM, and to evaluate any degree of concordance among them. Materials and Methods A retrospective evaluation was undertaken comparing DCG and VCU findings with definitive surgical findings in children who received both investigations for the initial management of ARM. Results In this study, 26 boys were included. Malformations were classified according to Krickenbeck classification. Four boys with perineal fistula were excluded from the analysis, as none of them needed a colostomy; therefore, comparison between both methods was not possible. VCU identified a rectourethral fistula in 12 cases, a rectovesical fistula in 4 cases, and excluded a fistula in 6 cases. VCU was false negative for a rectovesical fistula in one case. VCU showed a vesicoureteral reflux in 16 patients. Results obtained by VCU were compared with DCG. DCG showed a rectourethral fistula in 11 cases, a rectovesical in 3 cases, and excluded a fistula in 6 cases correctly. DCG was false negative in two cases, a rectoprostatic and a rectovesical fistula. The diagnostic accuracy, measuring the sensitivity was 95% in VCU (range: 76.18-99.88%) and 90% (range: 68.30-98.77%) in colostogram. Conclusion VCU can be as accurate as distal colostogram in the evaluation of male patients with ARM. VCU uses a natural orifice, without the need of a colostomy. VCU can be performed as an initial modality to determine the type of malformation and to decide on the type of early surgical management.

Improvements in Incontinence with Self-Management in Patients with Anorectal Malformations.

UNLABELLED: There are limited data available in children with anorectal malformation (ARM) regarding the use of transanal colonic irrigation delivered with the Peristeen system (Coloplast Denmark A/S, Humlebaek, Denmark). To our knowledge no study has combined the element of controlled evacuation with self-management strategies. Our center began offering this management regimen 5 years ago to patients suffering from fecal incontinence. The aim of this study was to appraise the results of this approach in children from 4 to 18 years with incontinence and fecal soiling secondary to ARM. MATERIAL AND METHODS: Bowel management was initiated with the help of hydrosonography to evaluate bowel motility and the volume of the enema. The Peristeen irrigation system was used. Anorectal irrigation was repeated every 24, 48, or 72 hours. A personal schedule was developed based on every patient's individual preferences. Irrigations were self-administered by the patient while sitting on the toilet. Patients were controlled for soiling, time needed for irrigation, time interval between irrigations 6 and 12 months after start of therapy, with further yearly follow-ups. RESULTS: A total of 40 patients aged between 4 and 18 years were evaluated. After 12 months of therapy, 32 patients were free of symptoms of soiling. Six patients were soiling occasionally. Two patients did not follow the therapeutic regime. The average time needed for irrigation was 35 minutes, with the lower limit of 12 minutes and the upper limit of 60 minutes, irrigations where done every 24 hours in 12 patients. Overall 25 patients irrigated twice every 48 and 72 hours to achieve a constant 7-day rhythm. One patient irrigated every 5 days. At follow-up after 2, 3, and 4 years success rates were stable. CONCLUSION: We suggest that colonic irrigation should be combined with self-management strategies in children with ARM. Adherence to therapy can be enhanced with the use of an individualized irrigation schedule. The amount of time required for the irrigation can be significantly reduced. Therefore, when establishing colonic irrigation in children and adolescents a focus should be placed on time-saving measures and self-regulation.

Animal and Human Bite Wounds.

BACKGROUND: 30,000 to 50,000 injuries are caused by bites in Germany every year. Dog and cat bites are common, human bites relatively rare. 25% of the victims are under age 6, and 34% are aged 6 to 17. METHODS: This review is based on pertinent literature retrieved by a selective search and on the authors' clinical and scientific experience. RESULTS: In small children, most bite wounds are on the head and neck; in older children and adolescents, most are on the limbs. Bite injuries range from trivial ones needing no medical intervention to major soft-tissue defects with the loss of functionally important structures. A bite can transmit unusual pathogens from the saliva into the wound. The risk of infection after a bite is 10-20%, and about 30-60% of the infections are of mixed aerobic-anaerobic origin. Prophylactic antibiotics are recommended only for wounds that are considered at high risk of infection in view of their type and location, the species of the biting animal, and the characteristics of the patient. CONCLUSION: Structured surgical management of bite wounds is the most important factor in the prevention of infection. High-risk wounds must be differentiated from trivial ones. Interdisciplinary management is advisable for wounds on the hands and face.

Occurrence of giant focal forms of congenital hyperinsulinism with incorrect visualization by (18) F DOPA-PET/CT scanning.

CONTEXT: Congenital hyperinsulinism (CHI) is a rare disease characterized by severe hypoglycaemic episodes due to pathologically increased insulin secretion from the pancreatic beta cells. When untreated, CHI might result in irreversible brain damage and death. Currently, two major subtypes of CHI are known: a focal form, associated with local distribution of affected beta cells and a nonfocal form, affecting every single beta cell. The identification of focal forms is important, as the patients can be cured by limited surgery. (18) F DOPA-PET/CT is an established non-invasive approach to differentiate focal from nonfocal CHI. OBJECTIVE: The purpose of this study was to identify possible limitations of (18) F DOPA-PET/CT scan in patients with focal forms nonfocal CHI. DESIGN: A retrospective chart review of 32 patients (from 2008 through 2013) who underwent (18) F DOPA-PET/CT and partial pancreatectomy for focal CHI at the reference centres in Berlin, Germany and London, UK. RESULTS: In most cases (n = 29, 90·7%), (18) F DOPA-PET/CT was sufficient to localize the complete focal lesion. However, in some patients (n = 3, 9·3%), (18) F DOPA-PET/CT wrongly visualized only a small portion of the focal lesion. In this group of patients, a so-called 'giant focus' was detected in histopathological analysis during the surgery. CONCLUSIONS: Our data show that in most patients with focal CHI (18) F DOPA-PET/CT correctly predicts the size and anatomical localisation of the lesion. However, in those patients with a 'giant focal' lesion (18) F DOPA-PET/CT is unreliable for correct identification of 'giant focus' cases.

Prenatal diagnosis and management of a massive fetal ovarian hemorrhagic cyst torsion with secondary fetal anemia.

We report the case of one of the largest prenatally detected fetal hemorrhagic cyst with ovarian torsion and fetal anemia leading to subsequent cesarean section delivery and further unilateral oophorectomy of the neonate. Usually, fetal ovarian cysts tend to resolve spontaneously within the first months after birth. There is no need of surgical treatment for such simple cysts. Routine sonographic examinations are obligatory, because in some cases complications such as massive hemorrhage, cyst rupture, or ovarian torsion with following infarction can occur. With the occurrence of these complex cyst signs by sonographic investigation, subsequent intervention should be considered by an interdisciplinary team.

[Treatment for fecal incontinence in patients with anorectal malformations. Introduction of a therapeutic approach]. / Therapie der Inkontinenz am Beispiel anorektaler Fehlbildungen Vorstellung eines Behandlungskonzepts.

UNLABELLED: Fecal incontinence is a serious problem that may lead to social segregation and psychological problems. Patients with anorectal malformations frequently suffer fecal incontinence even with an excellent anatomic repair. In these patients an effective management program with enemas can improve their quality of life. We want to present our experience with bowel management and anorectal irrigation as treatment for stool incontinence. MATERIAL AND METHODS: Patients who presented with soiling regardless of the type of anomaly were included in the study. The diagnostic program comprised a careful clinical history, physical examination, exact classification of the malformation and stool protocol. All patients suffering from true fecal incontinence were included in a bowel management program. These patients received oral polyethylenglykol to evacuate stool impaction. Than anorectal irrigation was initiated and repeated every 24 or 48 hours. Patients were controlled for soiling, time needed for irrigation and time interval between irrigations 6 and 12 months after start oftherapy. RESULTS: 40 patients aged 4 to 54 with a mean age of 15,95 years were evaluated. 12 months after start of therapy 32 patients were free of symptoms of soiling. 6 patients were soiling occasionally once or twice per week. 2 patients did not follow the therapeutic regime and therefore did not show an improved condition concerning soiling in the long run. The average time needed for irrigation was 45 minutes, irrigations where done every 24 hours in 12 patients. 25 patients irrigated twice every 48 and 72 hours to achieve a constant seven day rhythm. One patient irrigated every five days. DISCUSSION: Patients born with anorectal malformation and suffering from stool incontinece can be kept clean of stool if they are subjected to an adequate treatment.

Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study.

BACKGROUND: Although the survival of children and adolescents with malignant germ-cell tumours has improved greatly in recent years, the outcome remains poor for those with refractory or recurrent malignant germ-cell tumours. We aimed to determine whether objective tumour response could be achieved in patients with refractory or recurrent malignant germ-cell tumours with PEI-regional deep hyperthermia as salvage treatment. METHODS: Patients with refractory or recurrent non-testicular malignant germ-cell tumours after standard cisplatin-based chemotherapy were treated prospectively with PEI chemotherapy (cisplatin 40 mg/m(2), delivered intravenously on days 1 and 4; etoposide 100 mg/m(2), intravenously on days 1-4; and ifosfamide 1800 mg/m(2), intravenously on days 1-4) plus simultaneous 1-h regional deep hyperthermia (41-43°C) on days 1 and 4. Patients received three to four treatment courses at 21-day intervals until residual tumour resection was possible; they subsequently received one or two additional courses of PEI-regional deep hyperthermia. Local radiotherapy was given for incompletely resected tumours. Chemotherapy and hyperthermia toxic effects were assessed using WHO grading. The primary endpoint was the proportion of patients who had an objective response as assessed with Response Evaluation Criteria in Solid Tumors version 1.0 guidelines. Secondary endpoints were the event-free survival and overall survival after 5 years. This ongoing PEI-regional deep hyperthermia study (Hyper-PEI protocol) is registered at the German Cancer Society, number 50-2732. FINDINGS: 44 patients aged 7 months to 21 years (median 2 years 7 months) with refractory or recurrent malignant germ-cell tumours (nine patients with poor response, 23 patients with first relapse, 12 patients with multiple relapses) were included in this study. We identified 34 yolk sac tumours, eight embryonal carcinomas, one choriocarcinoma, and one dysgerminoma by histology analysis. Of the 35 patients who had sufficient clinical and radiographical data available for response assessment, 30 (86%) had an objective response to treatment (16 patients had complete remission and 14 had partial remission). 5-year event-free survival was 62% (95% CI 45-75), and 5-year overall survival was 72% (95% CI 55-83). The median follow-up of surviving patients was 82 months (range 9-195). WHO grade 3-4 neutropenia and thrombocytopenia occurred in all 181 chemotherapy cycles. Granulocytopenic fever, which required intercurrent hospital admission, was noted in 29 (66%) of 44 patients after 53 (29%) of 181 courses. Five patients experienced treatment-related grade-3 acute renal toxic effects. INTERPRETATION: A multimodal strategy integrating PEI-regional deep hyperthermia and tumour resection with or without radiation can successfully treat children and adolescents with refractory or recurrent malignant non-testicular germ-cell tumours. The long-term prognosis of patients with poor response or after first relapse was almost similar to those receiving first-line treatment. This strategy merits further investigation. FUNDING: Deutsche Krebshilfe eV, Bonn, Elterninitiative Kinderkrebsklinik Düsseldorf eV, the Barbara and Hubertus-Trettnerstiftung, and the Marie Quendt Fund.

Hirschsprung disease in the older child: diagnostic strategies.

BACKGROUND: Hirschsprung disease is usually diagnosed in patients who are younger than 1 year; but in some individuals it is found later in childhood. OBJECTIVE: This retrospective study is focused on clinical signs and symptoms of Hirschsprung disease in older children. MATERIALS AND METHODS: Patients with Hirschsprung disease were included in the study if they were older than 14 months at the time of diagnosis. RESULTS: Ten patients older than 14 months were diagnosed with Hirschsprung disease; 7 were males and 3 females. In all, 60% had a positive history of recurrent gastrointestinal infection with vomiting and hospitalization. In 6 patients, the final diagnosis was delayed because of unspecific findings in contrast enema. Rectal biopsy confirmed the diagnosis in all patients. CONCLUSION: Contrast enema is not a specific method for diagnosing Hirschsprung disease. Rectal biopsy alone confirms the diagnosis and provides a clear indication for surgery.

Miliary tuberculosis complicated by pulmonary cavitations and pneumothorax in a 14-month old boy.

Surgical management of tuberculosis is uncommon in children. We report a case of a 14-month-old boy with miliary tuberculosis and recurrent pneumothorax due to cavities in the left lung. This boy had no previous medical history and was referred to our hospital for a severe pneumonia. Initial chest radiograph showed bilateral miliary pattern. Direct microscopy of gastric lavage showed the presence of tubercle bacilli, providing definitive diagnosis. In spite of effective medication, his status rapidly worsened. A cardiac resuscitation was followed by intubation, and he required high-pressure ventilation for four weeks. He developed left pneumothorax, for which several drainages were performed. Computed tomography revealed a huge cavern system involving the entire lingula and surrounded by the left pneumothorax. Eventually, a massive enlargement of the initial cavity necessitated a thoracotomy and wedge resection.

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.