Paeds: Endocrinology (2) Flashcards
Causes of delayed puberty with short stature
- Turner’s syndrome
- Prader-Willi syndrome
- Noonan’s syndrome
Causes of delayed puberty with normal stature
- polycystic ovarian syndrome
- androgen insensitivity
- Kallman’s syndrome
- Klinefelter’s syndrome
Ages for classification of late puberty (both genders)
Ages at which a girl and a boy may be classified as ‘extreme’ delay in puberty
Girl → >14 y old
Boy → >16 y old
What’s the danger of congenital hypothyroidism?
If not diagnosed and treated within the first four weeks it causes irreversible cognitive impairment
Features of congenital hypothyroidism
- prolonged neonatal jaundice
- delayed mental & physical milestones
- short stature
- puffy face
- macroglossia
- hypotonia
Screening for congenital hypothyroidism
Children are screened at 5-7 days using the heel prick test
What’s a secondary hypothyroidism?
- where is the problem
- levels of TFTs
- problem is at the hypothalamus or pituitary gland
- Low levels of plasma TSH
- Low levels of plasma Thyroxine
*Requires the levels of FT4 and TSH for diagnosis
Would UK Neonatal Screening Programme pick up secondary hypothyroidism?
No.
If there is clinical suspicion of hypothyroidism, a full assessment of thyroid function is mandatory
How testing for congenital hypothyroidism is done in the UK?
- Midwife obtains sample on day 5-8 regardless of health and sends blood spot card by 1st class post clearly identified as newborn screening blood spot
- Laboratory analyses for blood spot TSH
- Each laboratory defines a cut off point which identifies an abnormal result
- Normal result, parents informed
- Abnormal result referred to clinician for confirmation
Causes of hypothyroidism in children
The most common cause of hypothyroidism in children (juvenile hypothyroidism) is autoimmune thyroiditis.
Other causes include
- post total-body irradiation (e.g. in a child previous treated for acute lymphoblastic leukaemia)
- iodine deficiency (the most common cause in the developing world)
Structure of adrenal gland
How to assess BMI in children?
- BMI assessment more difficult in children than adults
- body mass index (BMI) varies with age
- BMI percentile charts are therefore needed to make an accurate assessment
What to do next if BMI of a child is at:
- 91st centile or above
- 98th centile or above
- 91st centile or above → consider tailored clinical intervention if BMI
- 98th centile or above → consider assessing for comorbidities
Causes of obesity in children
- lifestyle factors → the most common cause of obesity in children
- growth hormone deficiency
- hypothyroidism
- Down’s syndrome
- Cushing’s syndrome
- Prader-Willi syndrome
Epidemiology of obesity in children
- Asian children: four times more likely to be obese than white children
- female children
- taller children: children with obesity are often above the 50th percentile in height
Consequences of obesity in children
- orthopaedic problems: slipped upper femoral epiphyses, Blount’s disease (a development abnormality of the tibia resulting in bowing of the legs), musculoskeletal pains
- psychological consequences: poor self-esteem, bullying
- sleep apnoea
- benign intracranial hypertension
- long-term consequences: increased incidence of type 2 diabetes mellitus, hypertension and ischaemic heart disease
Genetics and obesity (simply)
genetics plays a part but does not pre-destine us to be obese
Relationship of GH and IGF-1
- GH (via a complex cascade) initiates the release of IGF-I within many tissues but predominantly the liver and at the growth plate
- IGF-I acts in an autocrine and paracrine manner via the IGF-I receptor to stimulate cell proliferation and longitudinal growth
What other hormones can affect GH-IGF-1 system?
Many other hormones can affect the GH-IGF-I system or directly affect cell proliferation at the growth plate including:
- thyroid hormone
- vitamin D
- corticosteroids
What is the trigger for puberty to start?
- Puberty’s trigger lies in hypothalamus → secretion of gonadotropin-releasing hormone (GnRH)
- GnRH → stimulates the pituitary gland → release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
- LH and FSH → signal ovaries and testes to begin releasing the appropriate sex hormones → estrogens and testosterone, which launch the other signs of puberty in the body
Hormone release during late pre-pubertal years
- During the late pre-pubertal years gonadotrophin releasing hormone (GnRH) are secreted with increasing frequency, initially during sleep
- In the early stages FSH secretion is in excess of LH but as the amplitude of GnRH pulses increase LH secretion becomes predominant
What’s the earliest sign of puberty in females
Breast development or ‘thelarche’ is the earliest sign of puberty and coincides with pubertal growth spurt
What’s first sign of puberty in males?
The first sign of puberty in boys is change in testicular volume from 3 mls to 4 mls
Prognosis for delayed puberty
Many children with delayed puberty will eventually go through an otherwise normal puberty, just at a late age
Benign causes of delayed puberty
- child is just maturing more slowly than average, a condition called constitutional delay of puberty
* This condition often runs in families
- young girls who undergo intense physical training for a sport, such as running or gymnastics, start puberty later than normal
Indications for reviewing a patient with delayed puberty
- No breast development in girls by age 13
- No menstruation for five or more years after the first appearance of breast tissue
- No testicles development by age 14 in boys
- Incompletely developed male organs by five years after they first start to develop
Management of Turner’s syndrome
There’s no cure for Turner syndrome, but certain treatments can help cope with the symptoms and effects of this condition:
- Hormone treatments with growth hormone and/or other hormones can improve growth and help girls achieve taller heights in adulthood
- Estrogen replacement around the age of 12 or 13 may be initiated to stimulate the development of secondary sexual characteristics, such as breasts, and menstruation
- If structural heart defects are present, cardiac surgery may be needed
Is Turner’s syndrome inherited?
Most cases of Turner syndrome are not inherited.
- chromosomal abnormality occurs as a random event during the formation of reproductive cells (eggs and sperm) in the affected person’s parent
- an error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes
Mosaic Turner syndrome is also not inherited
- it occurs as a random event during cell division in early fetal development → as a result, some of an affected person’s cells have the usual two sex chromosomes, and other cells have only one copy of the X chromosome
Biochemical characteristics of Addison’s disease
- hyponatremia
- hypoglycaemia
- hyperkalaemia
- unexplained eosinophilia
- mild prerenal azotaemia (accumulation of urea and creatinine in the body)
Causes of congenital hypothyroidism
- anatomic defect in the gland
- an inborn error of thyroid metabolism
- iodine deficiency
Signs and symptoms of congenital hypothyroidism
- Infants with congenital hypothyroidism are usually born at term or after term
- Often, affected infants are described as “good babies” because they rarely cry and they sleep most of the time
Decreased activity
Large anterior fontanelle
Poor feeding and weight gain
Small stature or poor growth
Jaundice
Decreased stooling or constipation
Hypotonia
Hoarse cry
Physical findings O/E of congenital hypothyroidism
The physical findings of hypothyroidism may or may not be present at birth. Signs include:
Coarse facial features
Macroglossia
Large fontanelles
Umbilical hernia
Mottled, cool, and dry skin
Developmental delay
Pallor
Myxedema
Goiter
Diagnosis of congenital hypothyroidism
Diagnosis of primary hypothyroidism
- decreased levels of serum thyroid hormone (total or free T4) and elevated levels of thyroid-stimulating hormone (TSH)
- if maternal antibody-mediated hypothyroidism is suspected→ maternal and neonatal antithyroid antibodies
In neonate, does a combination of low T4 and normal TSH require treatment?
The combination of low or low-normal serum total T4 levels and a serum TSH within the reference range suggests thyroid-binding globulin (TBG) deficiency.
This congenital disorder causes no pathologic consequence but should be recognized to avoid unnecessary thyroid hormone administration (i.e. when thinking about congenital hypothyroidism).
