Congenital hypothyroidism usually secondary to dysgenesis (but maternal autoantibodies may coexist). Beware panhypopit! Defects in synthesis mostly AR, goitre may be present. Transient due to maternal drugs, receptor blocking antibodies.
Features are large anterior fontanlle (delayed bone maturity), thick big tongue, low hair line, dry sparse hair, hoarse cry (myxoedema cords), from 3/52 on. Others are umbilical hernia, mottling, cool peripheries. Later in life infantile proportions (short limbs), square jaw, increased lordosis, myxoedema of face/hands, patellar degeneration on XR.
Equivocal Guthrie (TSH 8-25) may be due to ectopic thyroid with faltering T4 secretion. Dual scanning with US & isotope confirms, so helps with deciding if genetics needed.
Treat with 25-50 mcg thyroxine in first year. Treatment is still associated with language delays, minor motor problems, visuospatial defects, and attention problems. Also, accelerated cranial growth and delayed bone age have been observed, especially in children given high starting doses. There is clearly a need to define the optimal dose of T4 to initiate therapy as well as the desirable levels of serum T4 to be achieved during long term therapy.
A number of studies have shown that a higher dose is beneficial in closing the IQ gap between moderate and severe forms of the disease. However, there is a possible increase in neurobehavioural disorder in children who have received higher dose regimens of thyroxine. Distinction must be made between the initial serum T4 at diagnosis, the starting dose of T4, and the maintenance serum levels of thyroid hormones in the outcome assessment. Higher baseline T4, early normalisation of TSH (before 3 months), initial T4 dose are good. A high starting dose of T4 (eg greater than 8mcg/kg/d) does not appear to be harmful in the long term despite some earlier fears. Archives of Disease in Childhood 2005;90:112-113. Do Bone age regularly to confirm maturation.
Associated with maternal TR abs ie Graves disease. TPO abs (Hashimotos) are associated with transient hyperthyroxinaemia in first week and jaundice rather than thyrotoxicosis. 1-10% of mothers with Graves disease will have overtly hyperthyroid babies, although the risk does depend on whether maternal disease is current, whether radioactive iodine or surgery were required, and maternal antibodies.
Present at birth or in first 10 days. Normal neonatal TSH is up to 15, T4 up to 30. If both are high, suggests acute phase response to illness. Can be exophthalmos, goitre, irritability, tachycardia, hypertension, sweating, diarrhoea/vomiting, HSM!, thrombocytopenia!, microcephaly! 25% mortality! Treat with sedatives, lugol solution (8mg tds), carbimazole, ?steroids/propanolol.
T4 and TSH are low in extreme preterms but also in sick preterms of any gestation esp with sepsis, steroid treatment, dopamine treatment. Negative iodine balance is seen in most preterms for at least 2/52 after birth (reserves probably only a few days). Iodine in povidone/iodine (not chlorhexidine, which is better antiseptic anyway), Omnipaque, Gastrograffin (but no alternative) and in breast milk eg after epidural - exposure to a big dose essentially switches off thyroid (T4 halflife 3-7/7)!
T4 supplementation trial showed benefit in neurodevelopment for under 28/40 but harm at 29 weeks! Pattern still evident at follow up at 10 years. Pediatrics. 2005 Oct 17; [Epub ahead of print]. I2S2= RCT of iodine supplementation on-going.
Genital appearance dependent on testosterone and DHT, but gender role behaviour dependent on testosterone and oestradiol. John vs Joan case challenged idea of "critical period" in early childhood in which gender is programmed, but an extreme example - change in gender identity occurs rarely, and is more common in conditions where there is spontaneous masculinization at puberty. In young children, genital appearance has only a minor effect on gender recognition, so choice should be made on prognosis for future psychosocial/sexual function, possible effects of prenatal hormones, and syndrome. Suboptimal medical therapy and lack of knowledge about condition may have a greater influence than the anatomic disorder.
Faisal Ahmed, Arch 2004;89
See also Common.
Glucose requirement can be calculated from the following formula:
Glucose requirement (mg/kg/minute) = Infusion rate (ml/hr) x % of glucose infusion x 0.1677/weight.
Remember to add glucose in oral feed - glucose content of standard infant formula is 7.2g/ 100ml, and of LBW formula is 8.6g/ 100ml.
Normal is 4-6 mg/kg/min, over 8 is suspicious of hyperinsulinism.
75 LGA newborns with hypoglycaemia followed up to age 4 - no late effects. Archives of Disease in Childhood 2005;90
For more details including investigations, see Endocrine page in general paediatrics.
Hyperinsulinaemic hypogycaemia is a common cause of persistent severe hypoglycaemia, and is associated with long term neurodisability and epilepsy. Can be congenital, due to unregulated beta cell function, else secondary to various other conditions eg:
Can present with severe hypoglycaemia in the newborn period despite good oral intakes, else more insidiously in infancy and childhood. Macrosomia (+/- hypertrophic cardiomyopathy and hepatomegaly) is a feature of fetal hyperinsulinism but is not always present, otherwise typical features of hypoglycaemia may be seen, including seizures. Cases secondary to IUGR/asphyxia tend to be transient, settling within a few days, but some have persistent symptoms for months before suddenly resolving!
Fasting or exertion are the usual triggers, but postprandial symptoms may reflect dumping syndrome (usually secondary to gastro-oesophageal surgery) or else hyperammonaemic hyperinsulinism (due to poor protein handling). A form of exercise induced hyperinsulinism exists that requires exercise testing to diagnose.
Insulinoma is more likely in later childhood. Can be part of a multiple endocrine neoplasia syndrome type 1 (ask family history).
Raised plasma hydroxybutyrylcarnitine and urinary 3-hydroxyglutarate are diagnostic of Hydroxy AcylCoA Dehydrogenase (HADH) deficiency.
Focal disease is associated with uniparental disomy in chromosome 11, whereas diffuse disease can be familial or sporadic. Focal disease can be managed by limited surgery, whereas diffuse disease needs near total pancreatectomy for any benefit. DOPA-PET scans can differentiate focal disease with a sensitivity of 88-94%, and are 100% accurate in localizing the focal lesion (Aberdeen does).
Management aims to achieve normal glucose levels, using Carbohydrate supplemented oral feeds plus IV fluids. A central line may be needed to give concentrated dextrose solutions, esp if chubby. Glucagon can be given IM in an emergency but may lead to paradoxical insulin release. Glucagon and/or octreotide can be given as infusions in resistant cases.
For ongoing treatment, diazoxide acts on K-ATP channels in beta cells. Chlorthiazide is synergistic in the neonatal period. Hypertrichosis is the main side effect of diazoxide. Some rare gene defects are resistant to Diazoxide! Feeding probs esp GORD common, partly due to all the NG/IV feeding.
Kapoor, Arch Dis Child 2009 PMID 19193661
Chromosome 11p problem, where IGF2 gene lies. Hemihypertrophy, macroglossia, ear creases/pits, exomphalos, umbilical hernia, visceromegaly.
At increased risk of tumours esp nephroblastoma, adrenal carcinoma, hepatoblastoma.
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