An unusual cause of bleeding in primary hypothyroidism.

A 10-yr-old female was referred due to prolonged bleeding lasting for a week following tooth extraction. She had heavy periods since she was 9. Her height was < 0.4th centile. Tanner staging was breast stage B3-4, axillary hair A1, and pubic hair P1. Thyroid function tests showed elevated TSH, low free T4, and negative anti-TPO antibodies. Gonadotrophins showed high FSH and a prepubertal LH. Prolactin was high and ovarian cysts were found on ultrasound. Further investigations revealed low von Willebrand factor (vWF) antigen levels, leading to a diagnosis of acquired von Willebrand disease. She was started on levothyroxine therapy, with normalization of vWF antigen levels, prolactin levels, cessation of her menstrual periods and resolution of ovarian cysts.

Feeding Problems Are Persistent in Children with Severe Congenital Hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is a rare but severe disorder of hypoglycemia in children, often complicated by brain injury. In CHI, the long-term prevention of hypoglycemia is dependent on reliable enteral intake of glucose. However, feeding problems (FPs) often impede oral glucose delivery, thereby complicating the management of hypoglycemia. FPs have not been systematically characterized in follow-up in a cohort with CHI. AIMS: We aimed to determine the prevalence, types, and persistence of FPs in a cohort of children with CHI and investigate potential causal factors. METHODS: FPs were defined as difficulty with sucking, swallowing, vomiting, and food refusal (or a combination) in an observational study in 83 children in a specialized CHI treatment center. The prevalence of FPs at diagnosis, 6, and 12 months after diagnosis were noted. Genetic mutation status and markers of severity of CHI were tested for association with FPs. RESULTS: A third of children with CHI had FPs (n = 28), of whom 93% required antireflux medication and 75% required nasogastric and gastrostomy tube feeding. Sucking and swallowing problems were present at diagnosis but absent later. Vomiting was present in 54% at 6 months, while food refusal was present in 68% at 6 months and 52% at 12 months. The age at commencing and stopping nasogastric tube feeding did not correlate with FPs frequency at 6 and 12 months. Children with FPs had severe hypoglycemia at diagnosis and required glucagon infusion more often [odds ratio (OR) (95% confidence intervals) (95% CI) 28.13 (2.6-300.1), p = 0.006] to normalize glucose levels. FPs were more frequent in those with diffuse CHI undergoing subtotal pancreatectomy [n (%) = 10 (35%) vs. 0 (0%), p < 0.001], in contrast to those with spontaneous resolution [6 (22%) vs. 32 (58%), p = 0.002]. Those undergoing focal lesionectomy also had reduced FPs at 6 months after diagnosis [OR (95% CI) 0.01 (0.0-0.2), R (2) = 0.42, p = 0.004]. These observations suggest that persistence of hyperinsulinism was associated with FPs. CONCLUSION: FPs occur in a significant proportion of children with CHI. Severe hyperinsulinism, rather than nasogastric tube feeding or medications, is the main factor associated with FPs.

Reduced Glycemic Variability in Diazoxide-Responsive Children with Congenital Hyperinsulinism Using Supplemental Omega-3-Polyunsaturated Fatty Acids; A Pilot Trial with MaxEPA(R.).

OBJECTIVE: Congenital hyperinsulinism (CHI) is a rare condition of hypoglycemia where therapeutic options are limited and often complicated by side-effects. Omega-3-polyunsaturated fatty acids (PUFA), which can suppress cardiac myocyte electrical activity, may also reduce ion channel activity in insulin-secreting cells. PUFA supplements in combination with standard medical treatment may improve glucose profile and may reduce glycemic variability in diazoxide-responsive CHI. DESIGN: Open label pilot trial with MaxEPA(R) liquid (eicosapentaenoic and docosahexaenoic acid) PUFA (3 ml/day for 21 days) in diazoxide-responsive CHI patients (https://eudract.ema.europa.eu/, EudraCT number 201100363333). METHODS: Glucose levels were monitored pre-treatment, end of treatment, and at follow-up by subcutaneous continuous glucose monitoring systems (CGMS) in 13 patients (7 girls) who received PUFA. Outcome measures were an improved glucose profile, reduced glycemic variability quantified by a reduction in the frequency of glucose levels <4 and >10 mmol/l, and safety of PUFA. All children were analyzed either as intention to treat (n = 13) or as per protocol (n = 7). RESULTS: Mean (%) CGMS glucose levels increased by 0.1 mmol/l (2%) in intention to treat and by 0.4 mmol/l (8%) in per protocol analysis (n = 7). The frequency of CGMS <4 mmol/l was significantly less at the end of treatment than in the pre-treatment period [556 (7%) vs. 749 (10%)]. Similarly, the frequency of CGMS >10 mmol/l, was also less at the end of treatment [27 (0.3%) vs. 49 (0.7%)]. Except for one child with increased LDL cholesterol, all safety parameters were normal. CONCLUSION: MaxEPA(R) was safe and reduced glycemic variability, but did not increase glucose profiles significantly in diazoxide-responsive CHI. The supplemental value of PUFA should be evaluated in a comprehensive clinical trial.

Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism.

INTRODUCTION: Neuroglycopenia is recognized to be associated with abnormal neurodevelopmental outcomes in 26-44% of children with persistent congenital hyperinsulinism (P-CHI). The prevalence of abnormal neurodevelopment in transient CHI (T-CHI) is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI. MATERIALS AND METHODS: A cohort of children with CHI (n = 67, age 2.5-5 years) was assessed at follow-up review and noted to have normal or abnormal (mild or severe) neurodevelopmental outcomes for the domains of speech and language, motor, and vision. Children were classified as P-CHI (n = 33), if they had undergone surgery or remained on medical therapy, or T-CHI (n = 34), if medical treatment for hypoglycemia was stopped. RESULTS: Overall, abnormal neurodevelopment was present in 26 (39%) children with CHI, of whom 18 (69%) were severe. Importantly, the incidence of abnormal neurodevelopment in T-CHI was similar to that in P-CHI (30 vs. 47% respectively, p = 0.16). The prevalence of severe abnormal neurodevelopment in speech, motor, and vision domains was similar in both T-CHI and P-CHI children. For this cohort, we found that the severity of disease [based upon maximal diazoxide dose (odds ratio 95% confidence intervals) 1.3 (1.1; 1.5), p = 0.03], and early presentation of CHI <7 days following birth [5.9 (1.3; 27.8), p = 0.02] were significantly associated with abnormal neurodevelopment. There was no significant association with gender, genotype, or the histopathological basis of CHI. CONCLUSION: Abnormal neurodevelopment was evident in one third of children with both T-CHI and P-CHI, early presentation and severe CHI being risk factors. Early recognition and rapid correction of hypoglycemia are advocated to avoid abnormal neurodevelopment in children with CHI.