TYPE 1 DIABETES_

Type I DM : destruction of pancreatic 13 cells by an

autoimmune process ( 98% of diabetic children )

Type 2 DM : insulin resistance followed by 13 - cell

failure

E- #-ns-

Both genetic predisposition G environmental triggers play a role.

Molecular

mimicry probably occurs between an environmental trigger { an

antigen on the surface of 13 . cells of the pancreas . Triggersinclude - enterovirql infections

- diet,

cow 's milk protein-

over nutrition

In genetically predisposed individuals this results in an autoimmune

condition that targets B- cells resulting in increasing insulin

deficiency .

Clinical Features

Early polydipsig- there are peaks of

classic2 polyuria + riaq presentation in spring {3 weight loss autumn months

- enuresis I secondary )- skin sepsis Diagnosis-

Candida G other infections - random blood glucoselate diabetic Keto acidosis > 11mmol 11

- acetone smell on breath - glycosurig- vomiting - ketosis

- dehydration t symptoms- abdominal pain§

- Kussmaul breathing- fasting blood glucose

- drowsiness s7mmol/L- hypovolaemic shock - 4

'

Hbaic

e-

Initial Managementintensive educational program

- patho physiology- insulin

- insulin injection- short human insulin analogues

- fastest onset da short duration- glucose monitoring- diet G exercise

- long human insulin analogues- short soluble human insulin

- sick day rules

- onset 30 - 60 min, peak z . qhrs

- hypoglycaemia- given 15 - 30 min before meals

- psychological impact- intermediate insulin

- onset 1 - lhrs, peak 4 - 12 hrs

Insulin can be given as continuous infusion of

rapid . acting from a pump or by injections .

€Rotation of the injection sites is essential to

thprevent lipo hypertrophy or more rarely lipo atrophy .

to

:itnineithiauaatbaesnpainngihe"

fto¥fBasal bolus regimen : #.

short actings

MB,||

.MN.

⇐ Anteing a-

Breakfast lunch Dinner Bedtime

insufficient insulin

insulin food

exercise Factors illnessdecrease increase

alcohol affecting menstruation

some drugs blood growth hormone

anxiety glucose steroids

not weather pubertystress

- Hbaic should be measured at least 4 times 9 year- c 48mmol lmol I 6. 5.1

.) is the recommended target

Acute Complications

Hypoglycaemia- most develop symptoms when blood glucose falls < 4mmol 11

- symptoms are highly individual 4 change with age but most

Complain of,

-

hunger- tummy ache

-

sweatiness-

feeling faint- dizziness- wobbly feeling in legs

-

manage with administration of easily absorbed glucose- glucagon injection kit for severe hypo 's

- if 4 consciousness

- IM administration- in patient managed with IV glucose

2 Diabetic Keto acidosis

Early investigations- blood glucose > 11.1mmol 11

- blood ketones > 3.0mmol 11

- UGE 's,

creatinine ( dehydration )

- ABG 's ( acidosis )- evidence of cause ( blood G urine culture )

- ECG for T - wave changes ( hypokqlaemig )-

weight 1 assess dehydration )

ManagementFluids : correct dehydration over 48 hrs 0.li

. Nacl

2 Insulin

3 Potassium

4 Acidosis : don't use bicarbonate

5 Re - establish oral fluids,

sub cut insulin G diet

6 Treat underlying cause

long . Term Complications- macro vascular

- HTN

- CVD

- coronary heart disease

- micro Vascular- retinopathy- nephropathy

-

neuropathy

CONGENITAL HYPOTHYROIDISMOccurs in 1in 4000 births with a ratio of 2 :|

,F :M

.

It is a preventable cause

of severe learning difficulties .

Aetiology- thyroid dysgenesis

185'll-

sporadic-

results in thyroid aplasialhypoplasia / ectopic thyroid- dyshormonogenesis ( 5 - lot

.

)

- inborn error of thyroid hormone synthesis- iodine deficiency

- Most common worldwide ,rare in UK

- congenital TSH deficiency ( < It.)

- usual'

y associated with pituitary dysfunction

Clinical Features

usually asymptomatic G picked up on screening .

Become more

prominent with age .

- faltering growth- large tongue

- feeding problems- hoarse cry

-

prolonged jaundice-

goitre- constipation

- umbilical hernia

-

pale , dry skin - delayed development-

coarse facies

DiagnosisNewborn blood spot screening test

- 4

TSH

! congenital TSH deficiency is not detected- thyroid imaging

- radio nucleotide scan

Managementnyroxine

- before 2- 3 WKS

- monitor TSHG -14 levels every 1-2 months in 1st year

CONGENITAL ADRENAL HYPERPLASIA

Family of autosomal recessive disorders characterised by defects in

steroid ogenic pathways that lead to biosynthesis of cortisol,

aldosterone G androgens .

The decrease in cortisol leads to 4' secretion

of ACTH via negative feedback causing hyperplasia of the adrenals .

Causes

-

21in - hydroxyl ase ( CYPZI ) s 90%

-

1113- hydroxyl ase ( CYPH )

- hx - hydroxyl ase ( CYP 17 )

.. . YACTH Mineral corticoids Corticosteroids

.

: 4' Cholesterol 9 Progesterone 417 . hydroxy progesterone.

: d, Aldosterone

tcortisola

: . . . . . . . . . .

'

. . . . . . . . in n' Testosterone

Clinical Features

enlarged penis less common in girls as alreadydiagnosed { started treatment

pigmented scrotum f,

salt - losing crisis in 80% of males- 1- 3wks Late presentation :

- vomiting In both male { female non - salt losers ( 20% )- weight loss

- tall stature- hypotonic - muscular build

virilisation -

pubic hairclitoral hypertrophy -

acne

labial fusion -

excess androgen- precocious puberty

Diagnosis- 1' nd . hydroxy progesterone levels

after 48hm of age- t '

21 - deoxycortisol- t '

urinary adrenocortisol metabolites

In CYPZI

- hyponatrgemia- hyperkalaemia

- metabolic acidosis

Managementf

additional during illness

Hydrocortisone oral gluco corticoid- replace cortisol

-

suppress ACTH

+ fludro cortisone in CYPZI mineral corticoid

- If resistant to hydrocortisone- Nacl solution

-

urogenital surgery- in infancy

- monitor growth ,bone maturity , androgens

- adrenal crisis

- urgent hydrocortisone- saline

- glucose

WEIGHT FALTERINGdef : suboptimal weight gain in infants or young children .

Growth is determined using WHO growth charts. weight faltering

describes a sustained drop down 2 centile spaces .

Causes Environmental Investigations- inadequate availability of food dietary history- psychosocial deprivation

- other symptoms ?

- neglect or child abuse - growth of

inadequate family members

Intake Underlying Pathology - FBC

- impaired suck / swallow - ESR

- cleft palate- CRP

-

Oro - motor dysfunction- UGE

- chronic illness → anorexia - creatinine

- CF -

total protein- crohn 's - albumin

- Cq2t

Inadequate - vomiting- POI

retention - GORD- LFTS

-

immunoglobulin- coeligc - short gut

- coeliac Ab 's

Mal absorption- CF - NEC

-

urinalysis- food allergy

- liver disease

consider- chromosomal disorders

-

Karyotype- IUGR

- sweat test

Failure to - extreme prematurity- CX ?

utilise - infection - bone age- metabolic disorders - serum lead ( pica )

- thyrotoxicosis- CF

Increased - ( k ,

requirements - CHD

- infection

GROWTH HORMONE DEFICIENCYGH is secreted by the anterior pituitary in a pulsatile manner .

Secretion

is diurnal 4 largely nocturnal 4 is controlled by 2 hypothalamichormones GHRH G GH - inhlt ( somatostatin )

.

Causes

Can be primary or secondary in origin .

Primary- idiopathic

- congenital hypopituitarism-

midline brain anomalies

Secondary- intracranial tumours

- cranial radiotherapy ( most common )-

psychosocial deprivation- traumatic brain injury

- inflammatory disease

- sgrcoidosis- intracranial haemorrhage

Clinical Features

Infancy-

hypoglycaemia-

prolonged jaundiceg

not GH - dependent- micro penis

- size at birth G growth during 1st year of life

Childhood- slow growth rate

- short stature

- 4'

subcutaneous fat- truncal obesity

- hyperplasia of mid - Facial bones-

delayed closure of anterior Fontanelle

Investigations- baseline / random serum IGF - I G IGFBP - 3

- GH provocation tests

all should be performed in the morning after an overnight Fast.

- insulin tolerance test ( gold standard,

?5 years )

! primarily a clinical diagnosis

Managementrh9H

- catch up on growth is optimal if started as early as

possible-

responses to dose assessed every 6 months

- continued until final adult height reached

PRECOCIOUS PUBERTYdef : early onset G rapid progression of puberty .

( 8 years females

< 9 years males

Causes

Central consequence of early physiological - idiopathicactivation of axis

.

A normal - intracranial tumours

sequence of pubertal development - CNS lesions

is observed .

- 20 central PP,

'

CAHG

McCune AlbrightPeripheral Due to mechanisms that do not - Mccune Albright

involve gonadal secretion from the -

gonqdgl tumours

pituitary . Endogenous production- CAH

independent of axis or exogenous .

- adrenal tumour

Abnormal sequence of development .

- HCG secreting tumours

- iatrogenic

Investigations- LHG FSH

-

oestrogen / testosterone

- 17 - OH progesterone ,DHEAS

- urine : steroid profile- x-ray- Pelvic US

-

Abdominal US

- MRI brain

- GNRH test

Management- detection da treatment of underlying cause

- t , rate of skeletal maturation- addressing behavioural G psychological issues

GNRH analogues

DELAYED PUBERTYdef : lack of initiation G progress of pubertal development

> 14 years females

s 16 years males low or undetectable

Causes gonadotrophic levels

Hypggonadotrophiohypogonadisnifcongenital

- Kallman 's syndrome- isolated LH or FSH deficiency- CAH

- acquiredgenetic disorder with HH

- intracranial tumours{ anosmig

.

- cranial irradiation- traumatic brain injury

- anorexia- excessive exercise

- chronic disease

2 Primary Gonadal Failure 1 hypergonadotrophichypogonadism )-

congenital- Turner 's

- Klinefelter 's

- gonadal dysgenesis- LH resistance

- CAH

- acquired- chemotherapy- irradiation-

gonadal infection- trqumg

Investigations- LHGFSH - BA X-ray-

oestrogen - Pelvic Us- testosterone - Abdominal Us

- Karyotype - MRI brain- TFTS - HCG

- CRP - GNRH

Constitutional DelayMost common cause

. Usually observed in boys .This condition reflects

a delay in timing mechanisms that regulate the onset of puberty .

Often q family history .

Often delayed or slow growth in childhood.

Management- short course of sex steroids-

boys : testosterone esters

incremental increases- girls : ethinylestradiol

progesterone should be added at menarche- aims

- 20 sexual characteristics- libido

- menstruation in females

- bone mineral isation

INBORN ERRORS OF METABOLISM

def : large group of rare genetic diseases that generally result from a

detect in an enzyme or transport proteins which results in a

metabolic pathway .

Presentation-

un expectantly severe presentation of an otherwise common infection-

significant metabolic acidosis- unexplained respiratory alkalosis-

hypoglycaemia

⇒cardiomyopathy

- liver dysfunction- drowsiness

,coma

-

early onset seizures-

dysmorphic features

- developmental regression- sudden unexplained death

Newborn ScreeningPKU

- learning difficulties- seizures- microcephaly

2 MCAD

- encephalopathy-

collapse-

non - ketotic hypoglycaemia3 GA -1 ( glutaric aciduria )

-

macrocephaly- encephalopathic crisis at 6- 18 mnths

→ dystonio - dyskinetic disorder

4 lsovqleric qcidqemig- metabolic acidosis

- hyperammonaemia5 Homocystinurig

- marfanoid appearance- learning difficulties

- lens dislocation- osteoporosis

- thrombo embolism

6 MSUD

-

progressive encephalopy in 1st week of life