Paediatric Endocrinology 1 Flashcards
What does growth hormone do?
Increases:
Adipose release of fatty Acids
Bone thickness
‘Creation’ i.e. linear growth, soft tissue growth, protein synthesis
‘Diabetes’ i.e. increased insulin resistance/BSL
Anterior pituitary hormones:
- Follicle Stimulating Hormone
- Lutenising Hormone
- Adrenocorticotropic hormone
- Thyroid stimulating hormone
- Growth hormone
- Prolactin
First sign of puberty:
Girls: breast buds, growth spurt
Boys: testes >3mL
Posterior pituitary hormones:
- Oxytocin
- ADH
What factors stimulate ACTH release?
- Environment (stress, fasting, hypoglycaemia)
- Arginine vasopressin
- Oxytocin
- Angiotensin II
- Cholecytokinin
What factors inhibit ACTH release?
- opioids
- atrial natriuretic peptide
What cells does LH act on and what are the downstream effects?
- female: theca cells, luteinization
- male: leydig cells -> increase cholesterol desmolase activity -> secrete testosterone, androstenedione and dehydroepiandrosterone (DHEA)
How does T4 help growth?
- facilitates GH release from pituitary
- promotes chondrocyte hypertrophy
What is the major cause for transient neonatal diabetes mellitus?
- Either paternal uniparental disomy of chromosome 6 or an unbalanced duplication of paternal chromosome 6
- Mutations of the imprinting gene ZAC/PLAGL1, a transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating polypeptide (an important regulator of insulin secretion), at chromosome 6q24
What is the major cause for permanent neonatal diabetes mellitus?
- 50% gene mutations related to the ATP-sensitive potassium channel (Kir6.2 or SUR1)
- Most commonly KCNJ11 gene encoding Kir6.2
- Also ABCC8 gene, which encodes SUR1
- Can treat with sulfonylureas
What is the genetic association with MODY3 diabetes?
- HNF1A on 12q24
- Progressive insulin secretory defect, renal glycosuria
What is the genetic association with MODY1 diabetes?
- HNF4A on chromosme 20q13
- Progressive insulin secretory defect. Foetal macrosomia, transient neonatal hypoglycaemia
What is DEND syndrome?
Developmental delay
Epilepsy,
Neonatal Diabetes - the most severe phenotype of Kir6.2 mutations
What is the genetic association with MODY2 diabetes?
- GCK on 7p13
- Stable mild fasting hyperglycaemia from neonatal life
- Asymptomatic/abnormal OGT/GDM/LBW.
- Microvascular complications rare
A 22 month old Caucasian boy with gross motor delay,
bowed legs and apparent bone pain on weightbearing.
Weight is on the 75th centile, while length is
on the 3rd centile. There is a history of dental abscess
in the family. He has been treated with cholecalciferol
without any improvement in his symptoms.
- X Linked Hypophosphataemic Rickets
Clues:
- Family history of dental abscesses. Due to low phosphate, individuals with XLH have teeth with short roots with enlarged pulp chambers
- male (therefore X linked)
If a child has rickets and normal PTH…?
Think phosphate issues
A 22 month old Caucasian boy presents with FTT and polyuria. On examination there are splayed
wrists, ankles and knees and bowed legs. Walking
was achieved at 18 months of age. Both weight and
length are below the 3rd centile. There is a family
history of miscarriage. He has been treated with
cholecalciferol without any improvement in his
symptoms.
Fanconi syndrome
If you see gelastic seizures and precocious puberty…
- Hypothalamic hamartomas are the commonest brain lesions to cause central precocious puberty and are associated with gelastic seizures
(laughing unexpectedly)
What are some common endocrinological changes in anorexia nervosa?
- hypothalamic suppression, low normal to low gonadotropin and sex hormone levels
- Decelerated linear growth, pubertal delay/regression, menstrual dysfunction
- Low IGF-1 and T4 levels
- Sick euthyroid if severely malnourished
- Reduced bone mineral density
What is the likelihood of spontaneous puberty in Turner Syndrome?
- 70% of Turner Syndrome patients will not go through puberty themselves
- 30% spontaneous puberty
- FSH should be measured prior to pubertal induction to confirm that it is elevated
What are the signs/symptoms of McCune-Albright syndrome?
- Endocrine dysfunction (precocious puberty in females; pituitary, thyroid and adrenal abnormalities also noted)
- Patchy cutaneous pigmentation
- Fibrous dysplasia of the skeletal system with normal or increased bone age
- LH is generally decreased, therefore increased FSH:LH -Ovaries contain multiple cysts, commonly having large solitary cyst
What does ketoconazole do to hormone secretion?
Inhibits C-17,20-lyase and testosterone synthesis
Which hormone makes a foetus male?
AMH
What is most important in controlling parathyroid hormone (parathormone) secretion?
SERUM calcium
but PTH increases IONISED calcium
What does diazoxide do?
- opens K-ATP channels
- increases adrenaline secretion
- increases gluconeogenesis.
What hormone inhibits prolactin?
Dopamine
What blood findings might there be in primary adrenal insufficiency?
- “Salt losing” i.e. low Na/high K
- High ACTH/low cortisol
- Short synacthen test - no response
Adjusted sodium calculation for hyperglycaemia:
Na + 0.3 (glucose-5.5)
Which gene is involved with McCune-Albright?
GNAS
How does metformin work?
- Increase insulin sensitivity
- less gluconeogenesis
Spikey hair, cleft, congenital hypothyroid…
- Bamforth-Lazarus syndrome
- TTF-2 gene
What is the dawn effect and which hormone is responsible?
- GH
- early morning rise in BSL
What do the different parts of the adrenal gland make?
- Cortex is affected in CAH i.e Cortisol, Aldosterone
- Medulla makes adrenaline MAD
- Reticularis (also cortex) makes androgens RANDY
Multiple endocrine neoplasia type 2 (MEN2) is a hereditary condition associated with three primary types of tumors:
- medullary thyroid cancer
- parathyroid tumors
- pheochromocytoma
(RET gene)
RET gene is….
MEN2
C-peptide is…
…stored and co-released with insulin, and is used to
evaluate possible excess endogenous insulin secretion
AIRE gene is….
- APS1
- Autoimmune polyendocrine syndrome type 1 but also known as autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism–Addison’s disease syndrome
- on chromosome 21
Hypoglycaemia awareness is due to…
adrenaline release
What percentage of beta cells need to be destroyed for T1DM?
80%
What controls PTH release?
Ionised calcium
What is the defect in osteogenesis imperfecta?
Type I collagen
What causes short stature in Turner Syndrome?
SHOX gene problem (not enough)
What endocrine abnormality can result from abusive head trauma?
Acute pituitary injury from intracranial haemorrhage or direct pituitary or pituitary stalk injury.
Why are XXY (Klinefelter) patients typically taller?
SHOX dose effect
How do you test for growth hormone deficiency?
IGF1 and IGF binding protein 3 as GH has pulsatile releases
How might IPEX present clinically?
- FOXP3 gene
- immunodysregulation polyendocrinopathy enteropathy X-linked
- e.g. lymphadenopathy, eczema (think EX for eczema), early diabetes, hypothyroidism (or other endo issues), diarrhoea
Until what age should male infants have similar testosterone levels to puberty?
- 6 months
- if low, hypogonadotrophic hypogonadism
What are the lab findings for 5-alpha reductase deficiency?
- low DHT
- high T
What are the lab findings in sick euthyroid syndrome?
- low or low-normal serum T4, low T3
- low to normal TSH
- secondary to nonthyroid illness e.g. anorexia
What do sertoli and leydig cells secrete?
- Sertoli - AMH, inhibin, androgen binding protein
- Leydig - testosterone
