Endocrine Flashcards
What are the types of Maturity onset Diabetes of the Young and features of each?
MODY 3 - most common type 60%
- due to defect in HNF-1 alpha gene
- associated with increased risk of HCC
- Diabetic retinopathy and nephropathy often occur
MODY 2 - 20% of cases
- Due to defect in glucokinase gene
MODY 5
- Defect in HNF-1 beta gene
- Associated with pancreatic atrophy, renal abnormalities, genital tract malformations.
Features of MODY?
Develop <25 years.
Family history of early onset diabetes often present
Ketosis is not feature at presentation
Patients with most common form are very sensitive to sulfonylureas, insulin is not usually necessary.
Causes of hypoglycaemia (metabolic, hormonal, hyperinsulism, neonatal)
Metabolic - ketotic hypoglycaemia, liver disease, inborn errors of metabolism
Hormonal - Addison’s disease, panhypopituitarism, GH def.
Hyperinsulism - islet cell adenoma, exogenous insulin.
Neonatal - maternal DM, prematurity, IUGR, hypothermia, neonatal sepsis, Beckwith-Wiedemann syndrome.
Symptoms of hypoglycaemia?
Faint, dizzy Sweating Coma Seizures Trembling Hunger Lethargy Bizarre behaviour
What is ketotic hypoglycaemia and what is the management?
Most common cause of hypoglycaemic episodes in non-diabetic kids (1-4)
Hypoglycaemia occurring in early morning due to normal fasting.
Make sure sufficient, regular carbohydrates, especially during intercurrent illnesses.
Spontaneous resolution usually occurs by ages 6-8.
Causes of hypothyroidism?
Maternal iodide deficiency
Developmental defects - thyroid agenesis, failure of migration
Dyshormonogenesis - error of thyroid hormone synthesis
Congenital pituitary lesions
Transient congenital hypothyroidism -due to maternal thyroid disease
Post total-body irradiation
What is screened for in newborn screening?
Day 5-7
Congenital hypothyroidism Cystic fibrosis Sickle cell disease Phenylketonuria Maple syrup urine disease (MSUD) Homocystinuria etc
Normal puberty in males?
LH stimulates Leydig cells in testes to produce testosterone and secondary sex characteristics, and FSH stimulates germ cell maturation leading to spermatogenesis.
- puberty starts with testicular enlargement (>4ml) at around age 12.
- Maximum height spurt at 14.
Normal puberty in females?
LH and FSH both stimulate follicular development in ovaries resulting in oestrogen secretion and secondary sexual characteristics.
- puberty starts with breast development and finishes at menstruation.
- Breast development at around 11.5 years.
Menarche at 13 (11-15).
What is precocious puberty?
Development of secondary sexual characteristics at an inappropriately young age:
<8 in girls
<9 in boys
Bilateral testicular enlargement - gonadotrophin release from intracranial lesions
Unilateral - adrenal cause (tumour or adrenal hyperplasia)
Types and causes of precocious puberty?
Gonadotrophin dependent (central, true):
- Premature activation of HPG axis
- normal pattern of puberty but at younger age
- Idiopathic (common in girls)
- CNS abnormalities - hydrocephalus, brain tumour, arachnoid cyst, secondary to surgery/irradiation.
Gonadotrophin independent (pseudo, false)
- Abnormal pattern of puberty due to increased sex steroids without activation of HPA-axis.
- Congenital adrenal hyperplasia (most common)
- Cushing syndrome
- Sex steroid secreting tumours (ovaries, liver, adrenals)
- McCune-Albright syndrome
- Testotoxicosis
- Exogenous sex steroids
Investigations for precocious puberty?
GnRH stimulation test (gold standard)
FSH and LH increased in gonadotrophin dependent (central)
FSH and LH decreased in gonadotrophin independent (peripheral)
Male - testosterone and hCG levels
Female - oestradiol
TSH, T4, DHEAs, 17-OHP, bone age, USS abdo/pelvis. MRI head.
Karyotyping
Management of precocious puberty?
Gonadotrophin dependent - GnRH analogues
Treatment of underlying cause.
Definition of delayed puberty?
Absence of secondary characteristics at 13 for girls and 14 for boys.
Causes of delayed puberty?
Hypogonadotrophic hypogonadism (central):
- Reduced FSH/LH and oestrogen/testosterone
- constitutional delay
- Hypothalamic/pituitary disorders
- Kallman’s syndrome (normal stature, gonadotrophin deficiency)
- Prader-Willi syndrome (short stature, undescended testes)
- Systemic disease/stress/starvation
- Hypothyroidism
- chronic conditions - CD, CKD, coeliac
Hypergonadotrophic hypogonadism (gonadal failure):
- increased LH/FSH, reduced oestrogen/testosterone
- variations of sex differentiation
- Turner syndrome (45XO) - short stature
- Klinefelter syndrome (47XXY) - normal stature
Testicular/ovarian damage (trauma, surgery, torsion, chemo, irradiation).
Investigations for delayed puberty?
Detailed history of growth, parental heights, onset of puberty.
Pubertal staging (testicular volume)
Examination to exclude systemic disease (coeliacs, CD)
First line - FBC, CRP, ESR, U&E, LFT, Bone profile, Coeliac screen, TSH, T4, bone age.
Second line - FSH, LH, karyotyping, early morning oestrodiol or testosterone
USS to identify gonads for ?variation of sex differentiation.
Management of delayed puberty?
Constitutional delay - no management
Hypogonadotrophic hypogoanism - induce puberty with either testosterone or oestrogen.
What is congenital adrenal hyperplasia?
Autosomal recessive.
Disorder of adrenal steroid biosynthesis - in response to low cortisol levels, anterior pituitary secretes increased ACTH, which causes increased androgen production from adrenals.
Features of congenital adrenal hyperplasia?
Cortisol deficiency - hypoglycaemia, cardiovascular collapse
Aldosterone deficiency - hyponatraemia, hyperkalaemia, volume depletion, shock
Increased androgens causes virilisation of female infants and precocious puberty in males.
Investigations of congenital adrenal hyperplasia?
Markedly evaluated levels of 17alpha-hydroxyprogesterone in blood.
Urine steroid profile
Hyponatraemia, hypochloridaemia, hyperkalaemia.
Management of congenital adrenal hyperplasia?
Salt-losing crisis - volume replacement with normal saline and systemic steroids.
Long term treatment -
- cortisol replacement - replaces hormone deficiency and suppresses ACTH and androgen overproduction
What is osteogenesis imperfecta? Symptoms? Complications? Management?
Autosomal dominant - reduced type 1 collagen.
Brittle bones, blue sclerae, short height, loose joints, hearing loss.
Cervical artery dissection, aortic dissection.
Management -
- no cure
- healthy lifestyle - exercise, avoid smoking, avoid contact sport
- supportive management - treat broken bones, physio, pain medication.
Features of Growth Hormone deficiency?
May present at birth with micropenis (in males), hypoglycaemia or severe jaundice in neonates.
Poor growth, short stature, slow development of movement and strength and delayed puberty.
Investigations for growth hormone deficiency?
Growth hormone stimulation test - insulin or glucagon given to stimulate GH. Then measured shortly afterwards to assess hormonal response.
There will be poor response.
Test for other associated hormone deficiencies.
MRI brain to look for structural pituitary or hypothalamus abnormalities.
Genetic testing.
X-ray can be used to determine bone age and predict final height.
Close monitoring of height and development.
Treatment of growth hormone deficiency?
Daily SC injection of growth hormone
Treatment of other associated hormone def.
