1. S.O.D. - The Impact of Late Diagnosis
Rebecca Mayers
RGN RSCN
Paediatric Endocrine Nurse Specialist
Great Ormond Street Hospital NHS Trust

2. Charlotte
NVD 42 weeks 3.76kg
SCBU – neonatal hepatitis & ABO incompatible
Transfer to KCH London
Discharged at one month
Under KCH until age 5
Squint repair Moorfields – March 2006
No allergies, no medications
Immunisations up to date
Born in Essex at 42 weeks (NVD) and weighing 3.76kg she was admitted to SCBU with jaundice and unspecified neonatal hepatitis and ABO incompatible. All babies with neonatal hepatitis should have their cortisol function tested.
Transferred to Kings College Hospital where she had a blood transfusion, liver biopsy, steroids and phototherapy. She initially had failure to thrive but was discharged home at one month. She remained under KCH until age 5 years
Recently under Moorfield’s Eye Hospital for squint repair and was noted to take a long time to recover from the general anaesthetic.

3. Referral Chronological age 9.696years Mainstream school
Physically active
Local investigations into short stature
Hypothyroid FT4=7.2 TSH 2.81
Low cortisols (random) 21, 66
Café au lait spots (? Neurofibromatosis type1)
A 9 ½ year old girl was referred to Professor Mehul Dattani from her local hospital after investigations into short stature where she was found to be hypothyroid (T4 = 7.2 TSH 2.81) and had low random cortisol levels (21, 66). She also had three café au lait spots. No treatment had been commenced. She attended mainstream school but was reported to be slightly behind in English and Maths. She swam regularly and was a keen dancer – disco and ballroom.

4. Admission Wt 25.6kg (>9th; -0.82) Ht 121cm (0.4 – 2nd; -2.33 SDS)
24hr cortisol profile
Karyotype
Thyroid function tests
Paired urine/plasma osmolalities
MRI brain
Glucagon test
She was initially admitted to the unit for karyotype, synacthen test, TFTs, 24 hour cortisol profile, IGF1BP3, paired osmolality, electrolytes and an MRI of her brain.

5. Results Karyotype 46XX,No NF1 gene mutation TSH 2.7mU/L <6.0 FT4
7.2pmol/l
12-22
IGF1
15ng/ml
44-167
IGFBP-3
0.54mg/l
Paired osmolality
plasma
290mOsm/Kg
Urine
1066mOsm/Kg Na
140mmol/l K
4.6mmol/l
urea
3.9mmol/l
creatinine
36mmol/l
35-70
GH peak
0.6 mU/L
Normal >20

6. Cortisol Profile Time Cortisol nmol/L 14:00 <28 18:00 32 20:00
22:00
00:00 38
04:00
106
06:00 64
08:00 46
10:00 31

7. MRI Ectopic neurohypophysis with an absent pituitary stalk.
Pituitary gland small.
Optic Nerves do not appear to unite normally in the midline resulting in a wide optic chiasm with a slightly abnormal configuration.
Right optic tract is small PP OC AP
PP – Posterior pituitary
AP – Anterior pituitary
OC – Optic Chiasm

8. Diagnosis Not NF1 Hypopituitarism MRI findings
Therefore diagnosed as Septo-Optic Dysplasia

9. Septo-Optic Dysplasia
Congenital Syndrome
Hypoplasia of the optic nerve
Hypopituitarism
Absence of the septum pellucidum/hypoplasia or absence of corpus callosum
Varying degrees of the condition
Rarely a mutation of HESX1 gene, only one found at the moment
Often diagnosed in infancy following a collapse from underlying illness or hypoglycaemia
Facts and figures – 1 in 10,000 (figures come from the Manchester endocrinologists)
Extremes – Can have no visual problems or be totally blind
Problems - Can have Diabetes Insipidus as well as being hypothyroid, cortisol deficient, GHD and need help with puberty.
Long term they can have obesity, sleep disturbance and autistic tendencies.

10. The plan Medications on discharge Hydrocortisone 5mg/2.5mg/2.5mg
Levothyroxine 25mcg
Emergency hydrocortisone kit
Commenced 0.6mg GH Saizen Easypod
Professor Dattani diagnosed Septo-Optic Dysplasia and a meeting took place to discuss this with the family and Endocrine Clinical Nurse Specialist. She was discharged home on hydrocortisone 5mg/2.5mg/2.5mg. Told to commence levothyroxine (25mcg) 48 hours after hydrocortisone. CNS discussed emergency management and liaised with school. She returned a couple for weeks later for a glucagon test and was found to be growth hormone deficient.

11. Steroid card

12. Emergency Injection

13. Medic Alert

14. Ongoing issues Age at diagnosis
No preceding illness so acceptance difficult
Life changing
Questioning the need for the treatment
Impact of late diagnosis: The family require ongoing support and a high level of input as they have found it hard to come to terms with the diagnosis. They are questioning the need for hydrocortisone and have had to had the diagnosis covered several times.
Because Charlotte had been well, the impact was greater.
Acceptance stages (Kubler-Ross)

15. References
Brook C, Hindmarsh P (2001) Clinical Paediatric Endocrinology, Blackwel Science Ltd.
Dattani M (2001) Septo-Optic Dysplasia: From Mouse to Man, Clinical Pediatric Endocrinology
Kelberman D, Dattani M (2007) Genetics of Septo-Optic Dysplasia, Pituitary