174 \200 s c i r t a d e a P i 1 Prevalence unknown as under-reported. See Urol Clin North Am 2008 35 47 2 Microscopy is m ore reliable than stix tests for nitrites & leucocytes: Effective Health Care 2004 8.6 175 Treatment and prevention of urinary infections Antibiotic treatment Age <3 months: IV amoxi cillin + gentamicin (below) or IV cephalosporin alone (p106). Child >3 months with uncompli cated low- er UTI: 3-day course of trimethoprim1 50mg/5mL, 4mg/kg/12h (max 200mg) PO pro phylaxis (see below), nitrofurantoin, or amoxicillin/co-amoxiclav \200 Avoid constipation \200 \200\200Oral \202 uids \200 Encourage full voiding \200 Repeat MSU. \200 \207Resistance to trimethoprim and ampicillin renders monotherapy insuffi - cient in some p laces. 532 If the child or infant is ill (pyelonephritis + septicaemia) and blind parenteral therapy i s needed, \200 gentamicin (5 \200\2237mg/kg/day) may be given in a once-a- day regimen (IM if IV access fails). In one study, children and infants were randomly assigned to once-dai ly gentamicin 5mg/kg/day2 or 2.5mg/kg/8h slowly IV, where kg = lean body weight if obese.2 There was no diff erence in effi cacy, nephrotoxicity, ototoxicity, or renal scarring. 533 If neonate >35 weeks postmenstrual age, 2.5mg/kg/12h IV, slowly: consider a longer course i f pre- mature (gestation <34 weeks). 534 Do levels.3 IV cefotaxime and co-amoxiclav are alt ernatives. Treating ureteric re \202 ux If prophylactic antibiotics fail, ureteric reimpla nta- tion can reduce re \202 ux, but scarring remains. Keep on antibiotic prophylaxis. Pre vention Just one episode of re \202 ux of infected urine may initiate renal scarring, so s creening for bacteriuria is useless: damage is too quick. But once a UTI is suggested (eg b y stix) treat it at once, before you know culture sensitivities, as renal damage may be abo ut to happen. Obtain 2 high-quality urine samples for analysis. Consider prophylaxis if rec urrent UTI, signi \201 cant GU anomaly/renal damage. Example: trimethoprim prophylaxis (2m g/kg at night, max 100mg), eg while awaiting imaging \200\224and sometimes inde \201 nitel y (optimum duration is unknown, but may be after 2 negative cystograms, if the indication i s re \202 ux). Consider screening siblings for re \202 ux. Prophylaxis can be stopped aft er re \202 ux has been ruled out if there is no scarring. s c i r t a i d e a P Surgical correction of moderate re \202 ux is \200\230unlikely to be bene \201 cial \200 \231, and in minor re \202 ux is \200\230likely to be harmful \200\231 (carefully made EBM phrases!) 1 Trimethoprim every 12h, eg if aged 6 weeks \200\2236 months 25mg; 6 months \200\2236yrs 5 0mg, 6 \200\22312yrs 100mg. 2 Assumes normal renal function; give lower dose if the patient is obese, based on lean body weight estimated by the 50th centile on weight-for-age charts . See OHCM p738. 3 Levels may not be needed if gentamicin is given for <72h (usually the ca se). One-hour post-dose (peak) serum gentamicin concentration should be 5 \200\22310mg/L (3 \200\2235mg/L for streptococcal or enterococcal endocarditis); pre-dose ( \200\230trough \200\231) concentration should be <2mg/L in neonates and <1mg/L in others on a once-daily r egimen (<1mg/L for streptococcal or enterococcal endocarditis \200\224BNF advice). In neona tes phlebotomy is diffi cult and causes anemia \200\224so an example of monitoring advice f rom one NICU is: No levels before 48h of therapy unless proven infection requiring gentamic in and one of: \200 Perinatal asphyxia \200 Congenital renal defects \200 Renal insuffi ciency (creatinine >133 mol/L, ie >1.5mg/dL). www.cop.u \202 .edu/ wppd/research/sample7. pdf Renal failure and some renal diseases Acute kidney injury AKI (Previously acute renal failu re): Characterized by a rapid rise in creatinine or development of oliguria/anuria. 535 Cau ses in developed nations AKI occurs secondary to cardiac surgery, bone marrow transplanta- tion, toxicity (NSAIDs, aminoglycosides, vancomycin, aciclovir and contrast ne- phropathy) and sepsis, 536 in the tropics causes include: diarrhea/dehydration (50%); 537 glomerulonep hritis (34%); drug-induced haemolysis in G6PD de \201 ciency (5%); snake bite (4%); haemol ytic uraemic syndrome (2%); myoglobinuria (OHCM p307). Severity: The pediatric RIFLE criter ia strati \201 es severity of AKI based on changes in creatinine, estimated creatinine cle arance and urine output. 538 ATN causes: \200 Crush injury \200 Burns \200 Dehydratio n \200 Shock \200 Sepsis \200 Malaria. Plasma chemistry: K+ \200\200; creatinine \200 \200; urea \200\200; PO4 3 \200\223 \200\200 or \200\211; Ca2+ \200\201; Na+ \200\201; Cl \200\223 \200\201. MSU: Are there red cell casts (=GN)? If no RBCs seen but Labstix +ve for RBCs, consider haemo/myoglobinuria (OHCM p307). Other tests: ECG, serum and urine osmo- la lity, creatinine, acid \200\223base state, PCV, platelets, clotting studies (DIC), C3, ASO titre, ANA (antinuclear antibody). Radiology: \200\207Arrange prompt abdominal ul- trasoun d. Are the ureters dilated (eg stones: 90% radio-opaque)? If so, urgent surgery may be requ ired. Treatment: Remove or reduce the cause promptly. \200 Treat shock and dehydration (p 234) \200\224then: \200 If urine/plasma (U/P) osmolality ratio is >5 the kidneys concentr ate well; the oliguria should respond to rehydration. If the U/P ratio is low, try for a di ure- sis: furosemide 2 \200\2235mg/kg/6h IV slowly, (get help if more needed). \200 Monit or BP. If BP \200\200 \200\200: nitroprusside (p177). \200 24h \202 uid requirement: Av oid overhydration. Replace losses + insensible loss 176 \200 s c i r t a d e a P i (12 \200\22315mL/kg). Aim for weight loss (0.5%/day). Give no K+. Monitor ECG. Tall T-waves and QRS slurring prompt urgent lower- ing of K+, with IV salbutamol 4 g/kg or 5mg nebulized (2.5mg if <25kg). A less easy to use alternative (i f >1month old) is glucose with soluble insulin. Also consider polystyrene sulfonate resins 0.5 \200\2231g/kg max 60g PO and calcium glu- conate (10%, 0.5mL/kg IV over 10min; monitor ECG: stop IVI if heart rate \200\201) to counteract electrophysiological eff ect of hyperka laemia. High-energy, low volume infant renal formulas may prevent \202 uid excess. \200 Conside r renal replacement therapy as soon as \202 uid overload occurs. Many centers now prefer continuous haemo \201 ltration to peritoneal dialysis. 536 \200 \200\207Improvement is ushered in with a diuretic phase. Haemolytic uraemic syndrome (HUS) Essence: Acute microang iopathic haemolytic anemia (schistocytes, burr cells, OHCM \201 g 2 p327 & \201 g 3 p32 3), thrombocytopenia , renal failure + endothelial damage to glomerular capillar- ies. Typi cal HUS (95%) is associated with diarrhea, atypical HUS (5%) is not (it is a disease of com plement dysregulation). 539 Typical HUS is more frequent in the summer months, and typicall y occurs in children <3yrs. It is associated with Shiga toxin producing E. coli type O157:H 7. 540 Other causes: Shigella, HIV, SLE, drugs, tumor, scleroderma, BP \200\200. Signs: Col itis \200\203haemoglobinuria \200\203oligur ia CNS signs \200\203encephalopathy \200\203 coma. LDH \200\200. WCC \200\200. Coombs \200\223ve. PCV \200\201. Mortal- ity: 5 \200\223 30%. ADAMTS13 helps with risk stati \201 cation. Treatment: Supportive. Get help. Antibiot ics, \201 brinolytics, and anticoagulation are not used. 541 Treat renal failure (above). Relapses in TTP may be preventable by steroids, splenectomy, or vincristine. Chronic renal failure Causes: Congenital dysplastic kidneys, pyelonephritis, glomerulonephritis, chronic infection, re \202 ux nephropathy; AKI leading to corti- cal necrosis. \200\207Monitor g rowth, BP, U&E, Ca2+ (often \200\201), PO4 The Child: Weakness, tiredness, vomiting, heada che, restlessness, twitches, BP \200\200, hypertensive retinopathy, anemia, failure to thri ve, seizures, and coma. Treatment: (See BOX). Talk with experts about haemodialysis & trans plants. 3 \200\223 (often \200\200). 177 Chronic renal failure: metabolic and other issues Get a dietician \200\231s help. Calorie n eeds may not be met if vomiting is a prob- lem. Eggs & milk may be appropriate (high biolog ical protein value). Provide protein at a level of 2.5g/kg/24h. Vitamin drops may be needed . Nasogastric or gastrostomy tube feeding has a role. Growth hormone therapy combined with optimal dialysis improves growth: see BNF. Acidosis is common, needing no treatment if seru m bicarb is \211 20mmol/L.1 Renal osteodystrophy: A bone disease resulting from poor miner alization due to renal failure, causing poor growth, muscle weakness, slipped epiphy- ses, bone pain, and bone deformity ( cranial nerve lesions). 542 It is like rickets and low bon e turnover osteomalacia (osteoblast and osteoclast activity \200\201) osteomalacia. If glo merular \201 ltration falls to \200\20525% of normal, compensatory mechanisms to enhance phosphate excretion fail; resulting hyperphospha- taemia promotes hypocalcaemia, so PTH ri ses, which enhances bone resorp- tion to release Ca2+ in an attempt to correct hypocalcaemi a. PTH \200\200 leads to marrow \201 brosis (osteitis \201 brosis cystica). Also, the f ailing kidneys cannot convert enough 25-hydroxycholecalciferol to active 1,25-dihydroxychol ecal- ciferol, so GI calcium absorption falls, so worsening hypocalcaemia. \201\227: Aim t o normalize calcium and \200\201associated hyperphosphataemia. Keep PTH within normal limi ts in predialysis children and 2 \200\2233 times over upper normal limit in those on dialys is. Avoid aggressive use of calcium-based phosphate bind- ers and vit D derivates to preven t PTH oversuppression and development of adynamic bone disease. NB: there is little pediatr ic experience with calci- mimetics, eg cinacalcet, that directly stimulate Ca2+-sensing rec eptors and potently suppress PTH secretion without increasing Ca2+. 543 s c i r t a i d e a P Hyperphosphataemia is treated with phosphate binders, eg calcium car- bonate taken just bef ore food. Dose: see BNFc section 9.5.2.2. This combines with dietary phosphate to form calc ium phosphate, which is expelled in fae- ces. If there are episodes of Ca2+ \200\200, sevel amer may have a role (a synthetic calcium- and aluminum-free phosphate binder). 544 If Ca2+ is low despite correcting serum phosphate, give 1,25-dihydroxycholecal- ciferol (ca lcitriol), eg 15 nanograms/kg/24h PO max 250 nanograms (increased in increments of 5ng/kg u ntil Ca2+ and alk phos are normal, PTH level is reduced to 200 \200\223400pg/mL). X-ray evi dence of healing rickets may also exist. Then reduce dose. SE: \200\201renal function, hyp ercalcaemia, and hyperphosphataemia. Because normal bone requires adequate levels of PTH to promote bone modeling, over- suppression of PTH must be avoided to avoid adynamic osteodys trophy. Anemia is common, and is the result of \200\201erythropoietin ( poor iron and fo - lic acid intake). A typical Hb is 6 \200\2239g/dL. Do not transfuse, as this suppresses e rythropoietin production. Erythropoietin may be indicated (sc in pre-dialy- sis and periton eal dialysis patients, and IV if on haemodialysis). \200 Hypertensive emergencies Get expe rt help. While awaiting this, use sodium nitroprusside 0.5 g/kg/min IVI, increased in 200 nanogram increments as needed, up to 8 g/kg/min IVI by pump (allows precise control). Prot ect from light. Monitor BP continuous- ly; \200\200dose slowly to the required level. CI: severe hepatic impairment. With- draw over \200\20620min to prevent rebound hypertension. If used for >1 day, cut dose to 4 g/kg/min IVI. Labetalol is an easy-to-use alternative, e g 0.25mg/ kg/dose IV, doubled every 15min (as needed) up to 3mg/kg/h IV; CI: phaeo- chromoc ytoma. 545,546 1 If pH \200\2057.2, bicarbonate may be needed (by IVI if arrhythmias): get help as respon se is unpredictable, and dosing is diffi cult. Typical oral dose: 1 \200\2233mmol/kg/day in divided doses; bicarbonate 500mg capsules \200\223 de \201 cit in mmol \211\210 0.3 \211\210 weight (kg) \211\210 base de \201 cit (mmol/L) have 6mmol of HCO3 or 0.5 \211 \210 weight (kg) \211\210 (20 \200\223serum HCO3 \200\223). Ask the ex- pert what proport ion of this de \201 cit should be given IVI and over how long.547 \200\223 (& Na+).[9B] Infant HCO3 \200\223). In children it is 0.5 \211\210 weight (kg) \211\210 (24 \200\223serum HCO3 Acute nephritis and nephrosis Acute nephritis Essence: Haematuria & oliguria ( BP \200\200 , uraemia) produced by an immune glo- merulonephritis (GN) in the kidney. Peak age: 7yrs . Uncomplicated presentation: Haematuria; oliguria; BP \200\200 (50%); periorbital oedema; fever; GI disturbance; loin pain. Complicated presentations: \200 Hypertensive encephalop athy: Restless; drowsy; bad headache; \201 ts; vision \200\201; vomiting; coma. \200 Ur aemia: Acidosis, twitching, stupor, coma. \200 Cardiac: Gallop rhythm, cardiac failure enlargement, pulmonary oedema. Blood tests: Urea \200\200 in \205\224; ESR \200\200; acid osis. Complement (C3 ) often \200\201 2 \200\2238 weeks after onset (not in Henoch \200 \223Sch nlein purpura). Also ASO titre, antinuclear fac- tor (ANA), anti-DNA antibodies (i f SLE suspected), anti-neutrophil cytoplasmic (ANCA) antibodies (if vasculitis suspected), syphilis serology, blood cultures, virology. MSU: Count RBCs, WBCs, hyaline, granular casts ; red cell casts mean glomerular bleeding. Skilled phase-contrast microscopy detects odd-sh aped red cells, signifying glomerular bleeding. This change may not be present at \201 rs t. 24h urine for protein and creatinine clearance. Check urine culture, and speci \201 c g ravity (normal range: infants 1.002 \200\2231.006; child/adult 1.001 \200\2231.035). Othe r tests: Renal ultrasound; renal biopsy, check platelets & clotting pre-op. Poststreptococc al glomerulonephritis (PSGN) presents 7 \200\22321 days after a streptococcal infection(pha ryngitis, impetigo) with gross haematuria (cola- colored urine) and oedema + hypertension, malaise, anorexia, fever and ab- dominal pain. Urine: Proteinuria, RBC casts oliguria. B lood: \200\200urea, \200\200creatinine, \200\201C3. Recent streptococcal infection shoul d be con \201 rmed (serum ASO titre). Typically, renal biopsy is not needed. \201\227: Na + restriction, diuretics, antihyper- tensives. Restrict protein in oliguric phase. Give pen icillin orally for 7 \200\22310 days. Check BP often. If encephalopathy, give nitroprusside (p177). Oedema resolves in 5 \200\22310 days; however, hypertension, haematuria and protei nuria may last for several weeks. Prognosis is very good (95% full recovery). Nephrotic syn drome (nephrosis) Oedema, proteinuria (>40mg/m2/h), hypo- proteinaemia hypercholesterola emia. In 90% the cause is unknown, but any of the causes of nephritis (above) can cause nep hrosis too. Histology: Usu- ally minimal change GN (often associated with allergy and IgE p roduction).1 Symptoms: Anorexia, GI disturbance, infections, irritability; then oedema (per iorbital, genital), ascites, oliguria. Urine: Frothy; albuminous casts; Na+ \200\201 (se condary hyperaldosteronism). Blood: Albumin \200\201 (so total Ca2+ \200\201); urea and cre atinine usually normal. Renal biopsy: Reserve this for older children with any of: haematur ia, BP \200\200, urea \200\200, if protein loss is unselective (ie large molecular weights as well as small), and treatment \200\230failures \200\231. SE: haematuria; haemato- ma. 5 48 n=111 Complications: Pneumococcal peritonitis or other spontaneous infec- tions. Conside r pneumococcal vaccination if >2yrs. Treatment: Get help. Limit oedema with protein-control led (3g/kg/24h) low-Na+ diet (<50mmol/24h). Consider furosemide 0.5 \200\2231mg/kg/8h slow IV/PO + spironolactone (1 \200\2233mg/ kg/24h PO, max 9mg/kg/24h if resistant \200\224use l ower doses in neonates). Pred- nisolone 60mg/m2/day (max 80mg) for 6 weeks, then 40mg/m2/48 h for \211 6 weeks. 90% respond in 8 weeks. If steroid toxicity and relapsing NS, consider cyclophosphamide, eg 2mg/kg/day for \211 8 weeks (SE: haemorrhagic cystitis; WCC \200\201 ). If still relapsing, levamisole may help. Steroid-dependent NS may be treated with ciclos porin. 549 Ciclosporin is nephrotoxic. 550 \200\207Monitor BP. Control minimizes later ren al failure. 178 \200 Causes of nephritis \200 \200 -haemolytic strep via a preceding sore throat Henoch \200\223Sch nlein purpura \200 Toxins or heavy metals \200 Berger \200\231s dis . (OHCM p708) \200 Malignancies \200 Viruses \200 Bacteria (IE/SBE; syphilis) \200 Renal vein thrombosis s c i r t a d e a P i 1 Acharya B 2005 Am J Nephrol 1 30. Genetic variations in the IL \200\2234 and IL \200\2231 3 genes may be associated with predisposition to nephritic syndrome with minimal change glo merulonephritis.551 179 Steroids in nephrotic syndrome In nephrotic syndrome, protein leaks from blood to urine thr ough glomeruli, causing hypoproteinaemia and oedema. Before steroids (and antibiotics), man y died from infections. Most children with nephrotic syndrome respond to corticosteroids, b ut many experience a relapsing course with recurrent oedema and proteinuria. Corticosteroid s reduce mortality to 3%, with in- fection remaining the most important cause of death. NB : steroids cause obe- sity, poor growth, BP \200\200, diabetes, osteoporosis, avascular nec rosis (hip), and adrenal suppression. 552 Steroid-resistant proteinuria and ACE-i Enalapril is used in courses of >2yrs: dose example: 1 month \200\22312yrs: initially 100 g/kg/day (monitor BP carefully for 1 \200\2232h; increase as needed to 0.5mg/ kg/12h (maximum). In o ne study, urine protein electrophoresis showed a re- duction of 80% and 70% in the total pr otein and albumin, respectively, after enalapril. Some patients become free of proteinuria. ACE-i are discontinued if renal failure occurs, eg during infections. 553,554 s c i r t a i d e a P Growth, failure to thrive, and short stature Is growth normal? is a key question in determi ning the health of a child. Take any opportunity to weigh and measure a child. A series of plots on centile charts (p224) shows if growth is slow (growth curve crosses the centiles). NB: the growth rate in mid-childhood is 5 \200\2236cm/yr; this accelerates at puberty (pea k height velocity) before epiphyses start to fuse. Failure to thrive means poor weight gain in infancy (falling across centile lines). Head circumference is pre- served relative to h eight, which is preserved relative to weight. In 95% this is due to not enough food being o ff ered, or taken. Worldwide, poverty is the big cause; in the UK it is diffi culty at home , neglect, unskilled feed- ing, or not enough breast milk (top-up bottles may be needed). I diosyncratic growth pattern is one cause, or normal child of short stature ( \200\201birthw eight, short siblings or parents) \200\224likely if he is a contented child. Be skeptical a bout reliability of data. Is the birthweight accurate? Was the child clothed during weighin gs? Length measurements are particularly error-prone: growth velocity is more useful than m easurements done at a one time. Issues to address: Feeding and maternal interaction are mos t important. Is the child anorectic or ravenous \200\224 \200\230hyperphagic short stature \200\231? 555 Also: \200 If breastfeeding, does he get a good mouthful of breast? (p124) \200 If bottle feeding, does the teat \200\231s hole allow milk to \202 ow through? \200 Does weight gain return if the child is removed from the family? \200 Is there evid ence relevant to child protection proceedings? Tests: Check feeding technique. It is a grea t skill to know when to investigate. It \200\231s better from the child \200\231s point of view to ask a trusted colleague \200\231s advice before painful tests. In one study only 39 of 4880 tests were helpful. 556 180 \200 Features to note: \200 Signs of abuse (p146) \200 Feeding patterns \200 Behavior \200 Activity level \200 Family \201 nances \200 Health and happiness \200 Chart f amily heights \200 Any parental illnesses? \200 Dysmorphic face s c i r t a d e a P i Options are: MSU (expect false +ves if bags are used; but avoid routine su- prapubic aspira tions); U&E/glucose, LFT, Ca2+, proteins, immunoglobulins, CRP, TSH; FBC; sweat test; urina ry amino organic acid chromatography; stools (MC&S sugar detection); CXR, renal or CN S ultrasound, skeletal survey for dwar \201 sm and abuse; jejunal biopsy; ECG/echo. In non -organic failure to thrive, studies favor weekly visits from trained lay visitors. 557 Shor t stature is a height <3rd centile (p224). Use the method shown on the charts to correct fo r mid-parental height (short stature may represent \200\230regression towards the mean \200\231 of their heights). \200\207Any chronic disease can cause short stature. Hypopitui tarism (an impor- tant cause of short stature) usually manifests af- ter age 2yrs: look for relative obesity, without any other explanation for low growth velocity (ie <25th centile; measure for \211 1yr, see p226). De \201 ciency of growth hormone (GH) is shown by an im paired rise (peak GH <15MU/L) after a stimulus (eg sleep or hypoglycaemia, induced by IV in sulin (OHCM p224), or an arginine stimulation test. Preschool screen- ing for short stature is the aim. To be eff ective, start synthetic GH early. Somatotropin example: 23 \200\2233 9 g/kg/day SC; expect growth velocity to \200\200 by \200\20650% from baseline in year 1 of treatment. Other pituitary hormones may also be de \201 cient (OHCM p224). Causes of h eight \200\200: Thyrotoxic; precocious puberty; Marfan \200\231s; homocystinuria. Causes of weight \200\200: Snacksetc; not enough exercise; hypothyroidism; Cushings \200\231; Prader \200\223Willi, p652; Bardet \200\223Biedl, p638; Cohen syndrome (hypotonia, obesity, promi nent front teeth; seizures); polycystic ovary, p252. 558 Typical causes: \200 Constitutional ( 80%) \200\224 if both parents short \200 Psycholo gical neglect \200 Poverty; physical abuse \200 Drugs: eg steroids \200 Genetic: eg T urner \200\231s or cystic \201 brosis Ineff ective diet (coeliac) \200 In \202 ammatory bowel dis. \200 Hypothyroidism \200 Infection (eg UTI; TB) \200 GH \200\201 (as above) \200 Rarities, eg Noonan, p650 Ethnospeci \201 c growth charts559 It is clear that some populations are inherently shorte r than others, and this poses problems when using UK90 growth charts (i.e charts for childr en >4); which are based on cohorts of UK children in the 1980s (see also p224). Consider th ese facts: \200 The Dutch are the tallest nation on earth (mean \200 height 1.84m): the tallest population group is the Masai people (eg in Tanzania and Kenya). \200 African an d Afro-Caribbean 5 \200\22311-yr-olds height is 0.6 standard deviations scores (SDs) great er than white children living in England. 181 Gujarati children and those from the Indian subcontinent (except those from Urdu- or Punjab i-speaking homes) have heights 0.5 SDs less than white chil- dren living in England. \200 Gujarati children \200\231s weight-for-height is 0.9 SDs less than expected for Afro- Ca ribbeans, or white children in England \200\224so Gujarati children \200\231s weight is 1. 5 SDs less than for white children living in England. \200 Urdu and Punjabi weight is 0. 5 SDs < expected for white UK children. \200 Published charts have centile lines 0.67 SDs apart; for height and weight shift s c i r t a i d e a P the centile lines up by 1 centile line division for African-Caribbeans. Re-label Gujarati children \200\231s weight charts, so the 0.4th centile becomes the 15th centile, and the 2nd weight centile becomes the 30th centile. \200 For most other Indian subcontinent groups, height & weight need shifting down, eg relabel the 0.4th & 2nd centil e lines 1.5th & 6th respectively. NB: Sikh children are taller and heavier than Caucasians. 560 \200 Body mass index centiles are said to be appropriate for African-Caribbeans, but recalculate as above for Indian subcontinent children, except for Gujara- ti-speaking chil dren (0.4th & 2nd centiles \200\2034th & 14th). Trends towards tallness with each generatio n occur at varying rates in all groups, so 3rd generation immigrants are taller than expect ed using 2nd genera- tion data. Intermarriage adds further uncertainty. NB: to print the ne w CDC charts, see www.cdc.gov/nchs/about/major/nhanes/growthcharts/clinical_charts.htm NB: obesity ( diabetes) in school children is a big public health issue. See p156 for preventi ng \200\230adult \200\231 diseases by measures starting in childhood. Some endocrine and metabolic diseases Hypothyroidism Thyroid hormone is necessary for growt h and neurologic development. Dysfunction may occur in the neonate, infant or during child- hood. Congenital: Thyroid scans divide these into 3 groups: athyreosis; thyroid dysgenesis ; dyshormonogenesis. Also remember maternal antithyroid drugs (p25, eg propylthiouracil). A cquired: Prematurity; Hashimoto \200\231s thyroiditis; hypopituitarism; X-rays; Down \200 \231s syndrome. Signs: May be none at birth \200\224or prolonged neonatal jaundice, widely opened posterior fontanelle, poor feed- ing, hypotonia, and dry skin are common. Inactivity , sleepiness, slow feeding, little crying, and constipation may occur. Look for coarse dry hair, a \202 at nasal bridge, a protruding tongue, hypotonia, umbilical hernia, slowly re laxing re- \202 exes, pulse \200\201, and poor growth and mental development if it has no t been picked up. Other later signs: IQ \200\201, delayed puberty (occasionally precocious) , short stature, delayed dentition. 561 Universal neonatal screening: Cord blood or \201 lter paper spots (at 7 days, from heel prick) allow early diagnosis (the \200\230Guthrie card \200\231). They do prevent serious sequelae. Act on high and low TSHs (may indicate pi tuitary failure). 562 Tests: T4 \200\201, TSH \200\200 (but undetectable in second- ary hyp othyroidism), 131I uptake \200\201, Hb \200\201. Bone age is less than chronological age. A s it is unwise to X-ray the whole skeleton, the left wrist and hand are most commonly used. There are a large number of ossi \201 cation centers. Each passes through a number of mor phological stages, and using comparisons with key diagrams from \200\230normal \200\231 po pulations, a rough bone age can be determined. There is no hard-and-fast answer to the ques tion of how much discrepancy (eg 2yrs) between skeletal and chronological years is signi \201 cant. Levothyroxine (LT4): Start neonates with 15 g/kg/day; adjust by 5 g/kg every 2 weeks to a typical dose of 20 \200\22350 g/day. <2yrs start with 5 g/kg/day (max 50 g) adjust by 10 \200\22325 g every 2 \200\2234 weeks; >2yrs start with 50 g and adjust by 2 5 g every 2 \200\2234 weeks (eg to 25 \200\22375 g/day; adult doses are reached by 12yrs) . 563,564 Ad- just according to growth and clinical state. Avoid high TSH levels. Those wit h athyreosis need the highest doses of T4 and the closest monitoring early on. Those with d ysgenesis and dyshormonogenesis need more attention later. Hyperthyroidism Typical child: P ubertal girl. Signs/ lab features: OHCM p210. Fine-needle cytology of goiters may show juve nile autoimmune thyroiditis. Carbimazole starting dose: 250 g/kg/8h. Adjust according to response. 565 Propylthiouracil: 2.5mg/kg/8h (/12h in neonates) PO until euthyroid \200\224t hen ad- just dose; expect remission in 67%. 566 Higher doses may be needed. Typical mainte nance dose: \205\223 \200\223 \205\224 of remission-inducing dose. Thyroid disease in preg nancy and neonates See p25. The glycogen storage disorders (GSD) result from defects in enz ymes re- quired for the synthesis and degradation of glycogen. Abnormal stores are deposite d in liver, muscle, heart, or kidney. In some types there are CNS ef- fects. Most types (th ere are >12) are autosomal recessives. There is consider- able variability in severity and prognosis. Early diagnosis and treatment are important for minimizing organ damage. Types i nclude: von Gierke disease (type I, p655), Pompe \200\231s disease (type II, p652), Cori di sease (type III \200\224hypo- glycaemia, hepatomegaly, with failure to thrive), Anderson di sease (type IV), McArdle disease (type V), Hers disease (type VI) and Tauri disease (type V II \200\224phosphofructokinase \200\201 \200\224like McArdle \200\231s, but with haemolysis and gout: diagnose by muscle enzyme assay). Treatment depends on type. 182 \200 s c i r t a d e a P i In McArdle \200\231s, (most common GSD in adolescents) the cause is myophos- phorylase de \201 ciency. Stiff ness and myalgia follow exercise. Venous blood from exercised muscle sho ws \200\201levels of lactate & pyruvate. \200\201phosphorylase staining in muscle biopsy con \201 rms diagnosis. There may be myoglobinuria. Treatment: No extreme exercise. Oral g lucose and fructose may help. 183 Inborn errors of metabolism and phenylketonuria (PKU) These are often diagnosed by a urine metabolic screen (eg amino acids, organic acids, carbo- hydrates, mucopolysaccharides \200 \224in deciding which tests to do, get help; interest the lab in your problem). Typical sig ns: diarrhea, leth- argy, respiratory distress, metabolic acidosis ( odd body smells), ja undice, hypoglycaemia, U&E imbalance, \201 ts, and coma. Features may be intermittent, an d provoked by crises (eg infec- tion; dehydration). In addition, look for: Urine amino acids \200\200 in: \200 Alkaptonuria \200 Canavan leucodystrophy \200 Cy stinosis \200 Cystathioninuria \200 Fructose intolerance \200 Galactosaemia \200 Ha rtnup disease \200 Homocystinuria \200 Hyperammonaemia Physical sign: Hepatosplenomegaly Eg amino acid and organic acid disorders, lysoso- Possible signi \201 cance: s c i r t a i d e a P mal storage diseases (Anderson \200\223Fabry disease1) Mucopolysaccharidoses, eg Hurler \200\231s syndrome, p646, gangliosidoses, mannosidoses Organic acidurias Many diseases, eg von Gierke \200\231s syndrome; MCADD2 See p216 Aminoacidurias, organic aciduria, cystinuria , lactic acidosis, storage diseases Coarse facies WCC \200\201, platelets \200\201 Hypoglycaemia Mental retardation Failure to thrive PKU (phenylalanine ketonuria) \200\224Cause: Mutation of phenylalanine hy- droxylase (PAH) gene (chromosome 1 \200\224autosomal recessive) leading to ab- sent or reduced activity of phenylalanine hydroxylase. Classic PKU leads to gradual mental impairment. The defect leads to \200\201CNS dopamine, reduced protein synthesis, and demyelination.567 Milder forms of hyperphenylala- naemia can occur with diff erent mutations to the same gene, or mutations to co-factor tetrahydrobiopetrin (BH4). Clinical features: Fair hair, \201 ts, ec- zema, musty urine. The chief manifestations is \200\201IQ (eg dyscalculia poor spelling \200\201cognition).568 Tests: Hyperphenylalaninaemia (reference interval: 50 \200\223120 m ol/L). Treatment instigated in infants with levels >360 mol/L \200\224to avoid \200\201IQ which may start with levels of >394 mol/L.569 Treatment: Get ex- pert help. Diet: protein substitute that lacks pheny lalanine but is enriched in tyrosine. Aim to keep phenylalanin e levels to <360 mol/L570 by prescribing arti \201 cial food substitutes (amino acid drin ks) to give <300mg \200\2238g of natural protein/day (depending on age and severity of phen ylalanine hydroxylase de \201 ciency).571 Hypomyelination may be proportional to degree of phenylke- tonaemia, but some studies fail to show stricter diets are associated with highe r IQs. Despite treatment, children are more prone to depression, anxi- ety, phobic tendenci es, isolation, and a less \200\230masculine \200\231 self-image.572 Adher- ence to the die t may be poor (it \200\231s unpalatable).573 Also, the diet may cause changes of questionab le signi \201 cance in levels of selenium, zinc, iron, retinol, and polyunsaturated fatty acids.574 Prevention of manifestations: Screen blood at 1 week (using a heel-prick and \201 lter paper impregnation \200\224the Guthrie test). Maternal phenylketonuria \200\207P reconception counseling is vital. Eff ects on the baby: facial dysmorphism, microcephaly, g rowth retardation, IQ \200\201. 1 Anderson \200\223Fabry disease may present with torturing , lancinating pains in the extremities ( abdomen) made worse by cold, heat, or exercise. It is a neuritis (vasculitis of the vasa nervorum). By adolescence, angiokeratomata appear (clusters of dark, non-blanching, petechiae) in the \200\230bathing trunk \200\231 area (e sp. um- bilicus & scrotum). Also: paraesthesiae, corneal opacities, hypohidrosis, proteinur ia and renal failure. It may respond to enzyme \200\224 ( \200 -galacotosidase is \200 \201). Carbamazepine may help the pain. 2 MCAD de \201 ciency is screened for in neonates on the same sample as for PKU & hypothyroidism. It \200\231s an au- tosomal recessive (muta tion of the medium-chain acyl-CoA dehydrogenase gene; ACADM; 1p31). Signs: hypo- ketotic hy poglycaemic coma; metabolic acidosis; LFT \200\200; medium chain dicarboxylic aciduria; \200\230SIDS \200\231. \200 : \200 \211\210 1 : 1. \200\224: avoid fasting; diet to giv e more calories from carbohydrates & proteins, while minimizing lipids. It is the chief inh erited disorder of mitochondrial fatty acid oxidation in N. Europe. Carrier rate: 1 : 65. Precocious puberty Puberty may start as early as 8yrs in girls and 9yrs in boys. Refer to a pae- diatric endocrinologist if onset before this. \200 : \200 \211\21010 : 1. 575 Ca uses may be central (gonadotrophin dependent, eg craniopharyngioma or pituitary tumor) or p e- ripheral (eg testis or adrenal problem, or HCG \200\200 from rare tumors \200\230anywhe re \200\231). Biology Think of each physical signs of puberty as a bioassay for a separate en- docrine event. Enlargement of the testes is the 1st sign of puberty in boys, and is due to pulses of pituitary gonadotrophin. Breast enlargement in girls and penis enlargement in boys is due to gonadal sex steroid secretion. Pubic hair is a mani- festation of adrenal a ndrogen production. Growth in boys accelerates when testis volume reaches 10 \200\22312mL ( if measured by comparison with orchidometer beads rather than ultrasound, expect overestima tes by up to 60%). 576 Girls start to grow more quickly once their breasts have started to develop. Stage 4 breast development is a prerequisite for menarche (in most girls). The bes t sign that precosity is pathological is when this consonance of puberty goes awry: in Cush - ing \200\231s syndrome, pubic hair is \200\230too much \200\231 for the testicular volum e; in hypothyroid- ism, the testes are large (FSH \200\200 as TSH \200\200 \200\200) while growth velocity is low. 577 184 Sexual signs may be obvious or subtle.1 Gynae- comastia may worry boys.2 One consequence is short stature caused by early fusion of epiphyses. Premature adrenal maturity (adrenarche) may presage insulin resistance. Ask about general hypothalamic dysfunction? Polyuria, poly dipsia, obesity, sleep, and temperature regulation. There may also be signs of ICP \200\200 visual disturbance. Rare causes \200 Stress (eg adoption) \200 CNS tumors/empty sella \200 Craniopharyngi oma \200 Thyroid disorders \200 Choriocarcinoma \200 Meningoencephalitis \200 McCun e \200\223Albright syn. \200 21-hydroxylase lack \200 Rare genetic defects s c i r t a d e a P i If onset is before 2yrs, suspect a hypothalamic hamartoma. LH receptor gene mutations cause sporadic or familial male gonadotrophin-independent precocious puberty. Tests Growth chart s; puberty staging (Tanner charts); CNS CT/MRI; bone age (skeletal X-ray); urinary 17-ketos teroids; karyotype; adrenal, testis & pelvic \200 ultrasound, T4; TSH; LH; FSH; HCG; AFP; GH; pituitary tests (OHCM p224); oestro- gen/testosterone (if no adrenal source of \200 \200testosterone is found, left vs right spermatic vein sampling may suggest one testis has a tiny Leydig cell tumor or hyperplasia). 578 Virilizing 21-hydroxylase de \201 ciency is con \201 rmed by \200\20017- hydroxyprogesterone on ACTH stimulation. 579 Management: a physiological approach Initiation of puberty depends on release from inhibition of neurons in the medial basal hypothalamus that secrete gonadotrophin-releasing hormone (GnRH), and o n decreasing hypo- thalamic-pituitary sensitivity to \200\223ve feedback from gonadal ster oids. These changes are accompanied by \200\200frequency and magnitude of \200\230pulses \200\231 of LH. GnRH pulses are needed for normal gonadal function. Continuous high levels of GnRH paradoxically suppress secretion of pituitary gonadotrophins; this forms the basis for treating precocious puberty with synthetic GnRH analogs (nasal or SC). There is a rever sal of gonadal maturation and all the clinical correlates of puberty (not for pubic hair, a s there is no change in the secretion of androgens by the adrenal cortex). There is deceler ation in skeletal maturation. Treatment is continued eg up to 11yrs. Families need reassura nce that the child will de- velop normally. Endogenous estrogen accelerates growth ( \200 & \200 ), as well as mediating \200 sexual characteristics: testolactone can help by \200\201its biosynthesis. Anti-androgens (eg \202 utamide) and spironolactone also have a role. 580 1 Eg in boys: rapid growth of penis and testes; \200\200frequency of erections; masturbati on; appearance of pubic hair; body odor; acne \200\224maybe a tendency to high IQ; \200 \200energy expenditure tantrums/impulsive anger; early occurrence of capacity for frank sexual imagery in dreams and daydreams; early capacity for erotic and sexual arousal in rel ation to visual imagery, visual perception, and tactile sensation. 2 There is often transie nt estrogen/testosterone imbalance early in \200 puberty. Try to avoid tests (test- oster one, oestradiol; gonadotropins; karyotype if testes <6mL). Reassure, and delay requests for mam- moplasty. This page intentionally left blank