Paediatric Endocrine Cases

Esko Wiltshire

•Nothing to disclose

Case 1: Amy, 18 days old• Presents with episodic stiffening of arms & legs,

with eyes rolling back, last 10-15 secs

• Associated with small spills (no haematemesis)

• Occurring more often after feeds, but not consistently

• Otherwise well apart from mild jaundice, afebrile

• Feeding normally

• No perinatal issues

• Thoughts?

• Initially diagnosed as GORD and treated with gaviscon then omeprazole

• No effect on episodes which became more frequent

• Reviewed – likely seizures.

• What would you do now?

Case History: Amy, 18 day old

Birth Hx

• IVF baby, 37 weeks gestation, Mo G3 P3

• PROM from 31wks, gestational diabetes

• ELUSC for breech presentation

• Bwt = 3.1kg

• Apgars 91, 95

• Fijian-Indian parents

• Breast-fed, gaining weight

Bloods

• Glucose = 3.8mmol/l N

• Ca2+ = 1.54 mmol/l decreased

• P = 3.92 mmol/l increased

• Mg2+ = 0.72 mmol/l N

• Albumin = 43 mmol/l N

• WCC = 8.9 N

• ALP = insufficient, then 370mmol/l

• 25OH Vitamin D and PTH pending

Diagnosis ?

• ? hypoparathyroidism

• ? Vitamin D deficiency

Initial Therapy

• IVI 10% Ca gluconate (0.3ml/kg)/1 hour

• Corrected Ca unchanged, 1.54 then 1.59

• Continued fitting

• Contacted endocrine

• Attempted repeat IVI Ca bolus+ calcitriol, but line tissued and unable to regain IV access

• Therefore transferred to tertiary hospital

On-going therapy (ICU)

• Femoral line

• IV Calcium infusion @ 10ml 10% Ca gluconate/kg/24 hours

• Oral Calcitriol 0.25mcg tds, later bd

• By following pm, corrected Ca= 2.25mmol/l, seizures had ceased, changed to oral Ca 50mg 4 hourly

• 25 OH Vitamin D level = 12nmol/l, PTH = 9.8pmol/l (0.5-5.0)

• Family bloods: (all vitamin D deficient)

• Cx- swollen Rt leg secondary to femoral line (no DVT)

• 1 week later, Ca, Mg, P all normal

On-going therapy (ICU)

• All treated with Stoss therapy:

• Amy 100000U stat

•Entirely preventable with good primary care

Presentation of Vitamin D Deficiency

• Hypocalcaemic seizure (<6 months)

• Rickets - Bowed legs, etc• Muscle weakness / gross

motor delay• Asymptomatic: Xray or

bloods• Increased risk of :

– Bone pain– Fracture- both in childhood

and later, due to osteopenia/porosis

Auckland

• Grant et al, Pub Health Nutr 2009;12:1893– Population based study greater Auckland, ethnically

stratified, chldren 6-23 months

– Random residential address start points with cluster sampling next 20 houses

– 995 children identified, 575 screened according to ethnicity specific sampling, 159 declined participation, blood obtained in 398, sufficient in 353

• 46/353 vitamin D < 27.5 nmol/L

• Vit D varied with age, season and ethnicity

APSU Study

• 398 children with Vit D deficiency rickets across Australia over 18 month period, (Jan 2006-July 2007)

• 4.9 cases per 100000/year in under 15 year olds

• 98% dark or intermediate skin colour, 75% refugees, duration breast feeding inversely related to Vit D levels in those under 3

Vitamin D and Health in pregnancy, infants and children and adolescents in Australia

and NZ: a position statement

•MJA 198(3), 2013 18 feb;pp 1-8

Recommendations

1.Sunlight exposure {varies with season and skin type)

2. Vit D sufficiency is >50 nmol/L (severe deficiency < 12.5)

3.Recommend measurement of 25-OH D, Ca, PO4 in children with risk factors for deficiency, with treatment both short term and a long-term prevention plan

4.Measure Vit D in pregnant women at first antenatal visit if risk factors. There is an arguement to screen all pregnant women in NZ

5. At least 600 IU Vit D in pregnancy – if < 50 then at least 1000U– An alternative is to give 1000 IU to everyone

6. Breast-feeding – 2000IU for mother required to raise low infant Vit D

levels

– Pragmatic approach is 400 IU Vit D for all breast-fed infants and either 1000 or 2000 IU to mothers depending on risk factors or low Vit D

Single-Dose, Nurse-Administered “Stoss” Therapy

• Oral: Cal-d-Forte (50,000 IU cholecalciferolchewable tablets)

– Oil Emulsion

Protocol for Stoss Therapy for rickets

• Correct symptomatic hypocalcaemia with IV Ca gluconateinfusion + calcitriol

• Stoss (Calciferol Strong 50,000 unit chewable tablets) -single nurse-administered dose

<3 yrs 150,000 units

3 - 12 yrs 300,000 units

>12 yrs 600,000 units

• Optimise Ca intake (diet + supplement 600mg/d)

• Repeat blood levels (Ca, alb, ALP, 25OH-D, PTH) @4 wks & repeat Stoss if not normalised

• Repeat blood levels every 6 months

• Check knee/wrist XR for healing in 6 months

Summary • D deficiency widespread early in life

• Preventable with good primary care encompassing pregnancy and early childhood

• Sunlight provides ~80-90% and diet ~10-20% in Australasia

• Single-dose, nurse-administered Stoss Rx is safe & effective treatment for rickets

• Population prevention requires antenatal assessment and treatment, supplementation for breast-fed babies (± mother), & targeted screening of at-risk groups

Case 2: Emily

• Emily is a 4 year old previously well girl whose family attend your rural general practice

• She has started wetting bed again – a week ago, and past 3 nights– Toilet trained at 2 and a half

• What else would you like to know and what would you do at this point?

• What do you notice about her?• What else would you assess on examination?• What is your initial management?

Emily cont

• You note her abnormal respiratory pattern– Acidotic

• She has normal tissue turgor

• Her peripheries are cool with delayed perfusion

• Her pulse is 160

• Her blood pressure is 98/55

• She is able to follow brief commands and asks for her mother but is irritable when examined

• Her blood glucose at the bedside is 29 mmol/L

•What would you like to do with her at this point?

Case 2: Emily cont

• Its now two years later, Emily and her family are doing well.

• Emily’s mother rings you one Saturday morning because she has vomited twice during the night and had a large, watery, foul-smelling bowel motion that morning. She has not yet had any morning insulin. She wants to know what to do.

Case 2

• What other information would you need to assess this situation?

• What advice would you offer Emily’s mother?

Progress

• You advise her to test her urine or blood for ketones, give him a reduced dose of long-acting insulin, and to give small amounts of short acting insulin if he is high (>10-12) and/or ketotic

• You also advise her to offer him frequent carbohydrate containing fluids

• You advise that admission may be needed if he develops significant ketosis, has on-going vomiting or develops hypoglycaemia

• You ask her to remain in close contact with you (i.e. to ring again in 2-3 hours, or if anything changes)

Case 2

• She follows your advice

• Initially Emily tolerates fluids reasonably

• 4 hours later however he has a series of vomits

• His blood sugar is 2.5

• What would you do now?

• Treat the hypo– 0.3 g/kg orange juice/glucose/mentos

• Consider low dose glucagon:– Make it up and draw dose into an insulin syringe– Dose 2 “units’ (20 micrograms) if under 2 years age, 1

“unit”/year of age (10 micrograms/year of age) thereafter, max 15 units (150micrograms)

– Repeat double dose if glucose not significantly increased after 20 mins or recurrent hypoglycaemia

– Lasts in fridge up to 24 hours• Haymond et al, Diab Care 2001; Hartley et al J Paed Child Health

2006

0

0.5

1

1.5

2

2.5

3

t=0 t=2 t=5 t=10 t=15

mmol/L

Mean change in blood glucose over time

Glucose tablets

Just Juice (Orange)

Jelly beans

Mentos dragees

P= 0.034 at 10mins and p= 0.005 at 15 mins between the groups

Case 2

• Emily improves with low dose glucagon, BSL up to 5.5 mmol/l and her vomiting seems to settle.

• However 5 hours later you get another phone call – she hasn’t eaten and his BSL had dropped again to 2.8 mmol/L. She was about to call you, but as she went to the phone he had a fit

• She’s in a panic and can’t remember what to do

• What would you do now?

Case 2

• You talk her through giving the full dose glucagon injection (0.5 mg), and Emily comes around quickly.

• Her blood glucose 15 mins later is 6.2 mmol/L

• What would you do now?

• Glucagon causes nausea

• It also discharges all the glucose stored in the liver

• Any child given glucagon MUST be observed in hospital for at least 6-8 hours afterwards, and eat well enough during that time to re-establish their liver glycogen (which also requires some insulin!)

• Further hypoglycaemia in this period can only be treated with IV glucose.

Case 3: John

• You are a lead maternity caregiver. Mrs G has recently had her first baby, John.

• John was born vaginally after a normal pregnancy at 41 weeks

• He has not appeared unwell, but has had some jaundice and feeding has been a bit slow

• He has put on weight

Case 3: John

• You receive a call from the national testing centre when John is 8 days old, saying the TSH on the Guthrie card collected on day 3 is elevated at 60 mU/L

• What would be important to assess further in John?

• What is your management plan?

• What are you going to tell the parents?

Case 1

• Review History

• Examination features

• Confirmatory Laboratory Diagnosis

• Specific diagnosis

• Start Treatment

History

• Poor feeding/suck

• Lethargy

• Hypotonia

• Jaundice

• Constipation/GI symptoms

• Hypothermia

• Iodine exposure

• Maternal (or FH) thyroid disease/autoimmune disease

• Prematurity/illness

Examination

• Temperature

• Jaundice (unconjugated)

• Coarse facies

• Large Tongue

• Hypotonia

• Abdominal distension

• Goitre

• Associated malformations

Investigations

• Formal thyroid function tests

– Free T4 7 pmol/L

– TSH 90 mU/L

• What are the possible causes?

• How would you sort them out and why?

Diagnoses

• Congenital hypothyroidism (permanent)– Athyrotic

– Ectopic thyroid

– Dyshormonognesis (defect in metabolism thyroxine)

• Maternal thyroid autoimmunity

• Iodine exposure

• Transient Hyperthyrotropinemia

Management

• Thyroxine replacement– Frequent dose adjustment

– Normalise T4 quickly

– Liquid thyroxine -issues

• 10-15 g/kg/day initially– Around 50 g/day initially in a baby with athyrotic

congenital hypothyroidism

Congenital Hypothyroidism

• Birth Incidence 1 in 3000-3500 (worldwide)

• Severe intellectual disability untreated (lose 4-5 IQ points per month without treatment)

• Outcome with early treatment is excellent

• Screening from late 1970s

• intellectual disability prevented in ~ 830Australasian children every 10 years

Newborn Screening in New Zealand

• PKU

• Congenital hypothyroidism

• Cystic fibrosis

• Congenital Adrenal Hyperplasia

• Galactosaemia

• MSUD

• Biotinidase

• Tandem mass Spectrometry – amino acid,fattyacid oxidation and organic acidemias

Case 4: Sarah

• 13 year old girl presents to you with a lump in her neck– Anterior

– Gradually increasing in size over last 6 months

– No pain

– No recent illness

– Consistent with a goitre

• What other history would be important and what would you specifically assess during your examination?

Case 4: Sarah cont

• History– Symptoms hypo/hyper-thyroidism

– School performance

• Examination– Characteristics of goitre

– Lymphadenopathy

– Growth

– Pulse/BP/murmur

– Eye signs

• What would you do now?

Case 4 Cont

• Free T4 60 pmol/L

• TSH < 0.01 mU/L

• Thyroid autoantibodies– TSI (need to request specifically)

• Do you need to arrange imaging?

Case 4 Cont

• She and her family are going on a long-planned trip to China in 3 weeks time (and will be away for 4 weeks).

• How are you going to manage her from here?

Case 4 Cont

• Treatment– Carbimazole (not PTU)

– Radioactive Iodine

– Surgery

• Info re rare side effects of carbimazole– Letter

Case 4 Cont

• Remission with Carbimazole

• Stopped treatment last summer– Has remained in remission

Vitamin D Preparations

• Vitadol-C (400 IU Vit D/10 drops, +Vits A/C)• “Pentavite” = Cholecalciferol 200 units/5ml

(liquid) or 400 units/0.45ml (drops) + vitamin A• “Blackmores D3” = Cholecalciferol 1,000 unit

capsules• Ostelin (1000 IU/0.5 ml)• Alfa-calcidol (One-alpha) – 1-hydroxylated

vitamin D• Calcitriol (Rocaltrol)• Cal-D-Forte – 50000 IU/tablet

% Subjects with glucose ≥ 4 mmol/L

Glucose J beans Juice Mentos Total P value

2 mins 17% 22% 18% 10% 17% 0.52

5 mins 25% 20% 34% 21% 25% 0.37

10 mins 59% 48% 66% 54% 57% 0.35

15 mins 86% 74% 80% 91% 83% 0.1