Dr Susannah Pye | Dr Vaseem Hakeem
Suspected precocious puberty is a common reason for referral to the general paediatric clinic. Figuring out whether the signs you see in front of you are ‘normal variants’ is often half the problem when thinking about whether the child needs investigation.
Firstly, does the definition ‘precocious’ actually apply to the patient in front of you? The first signs of puberty are considered normal for any boy >9 years and girl >8 years. Secondly, is the developmental feature in question isolated, or are there other signs of progression into puberty? True puberty is only when there are breast buds (in girls) or testicular enlargement (in boys). There are plenty of benign conditions that don’t need further investigation, and the child and family can be reassured. We’ll spend a minute and quickly consider those now.
- Breast budding in the neonate – very common. Caused by maternal hormonal influence on neonate. Usually resolves within a few weeks but may last up to a couple of months. There may be some fluid discharge (sometimes colloquially called ‘Witch’s milk’!) – this is also normal and doesn’t warrant any treatment. Resolution is within a few weeks.
- Pubic hair of infancy – again associated with mildly elevated levels of DHEAS which resolved within 6-24 months
- Premature thelarche – early signs breast development in girls (usually <3 years old). There is often only a small amount of breast tissue which can fluctuate over time, but generally resolves by age 3 years.
- Premature adrenarche – most common in African-American or Hispanic children. This presents as pubic and axillary hair and there may also be body odour from apocrine sweating. There is no rapid progression of symptoms. A bone assessment here is often a good idea to reassure you that there isn’t any possibility of late onset CAH.
- Prepubertal vaginal bleeding – can occur on an single occasion or happen more frequently. Hormone panels point towards a prepubertal state, and the symptoms generally resolve. This is usually a diagnosis of exclusion, so it’s best to think of this at the bottom of your differential!
If the child does classify as having precious puberty, the next question is whether you think this a centrally (gonadotrophin dependent), or peripherally (gonadotrophin independent) driven process.
|Fundamentals||Gonadotrophin dependent||Gonadotrophin INdependent|
|What causes it?||Central pituitary tumours or congenital abnormalities||Tumours – testicular, ovarian and adrenal, or as part of a syndrome (ie McCune Albright)|
|Which tests tell me if there is a problem?||High LH/FSH||Low LH/FSH
High oestradiol or testosterone
So, if you see a child in clinic with suspected precocious puberty, what should you do?
How quickly did the features develop? Rapid development of physical features over a six month period are generally considered significant. Has there been a recent growth spurt? Try and plot their growth on a chart. Make sure you find out when parents started puberty, especially enquiring about when mother started menarche for female patients and growth patterns for siblings.
It’s really important to do a full systemic examination and include a Tanner staging assessment within that. Have a look to see if there are any birth marks, or evidence of adrenal excess.
What if you’re just not sure if you need to investigate the child?
Often the child in question might be 7 or 8 years old, with a few early signs of puberty and it’s tricky deciding what to do next. The patient doesn’t quite fit a diagnosis of a benign, variant condition but it’s difficult to decide if you should go ahead with blood tests and a hormone profile. In these circumstances, a quick trip to x-ray for a bone age assessment can be a reassuring way to support whether further investigations are required. Remember to request X-ray of left hand and wrist….not just ‘wrist X-Ray! The aim is to specifically look at the ossification pattern of small bones in the hand. Usually a bone age assessment more than two standard deviations of the child’s age is highly suspicious and warrants further investigation.
Which blood tests should I request?
If a child looks like they have the classic hallmarks of precocious puberty, it’s best to let a local consultant know before bleeding the child. Often, blood tests are missed or the wrong this is requested. It’s best to run it past the endocrine specialist first as they’ll be following the child up in clinic!
Saying that, it’s good to have some idea of the tests that might be required and how they should be interpreted.
|How do I interpret the result?|
|Basal LH + FSH||High LH/FSH suggests activation of HPA and increased GnRH. A central cause for precocious puberty is therefore more likely.|
|Oestradiol||If these hormones are high, LH and FSH levels may be suppressed. This points to a peripheral cause for PP.|
|Testosterone||Levels may be high if suspecting a testicular tumour in boys, or adrenal pathology in boys and girls. Sending DHEAS (dehydroepiandrosterone sulfate) can help to assess if the elevated testosterone level is secondary to adrenal pathology.|
|Human chorionic gonadotrophin||Always send this off for male patients to rule out an hCG secreting tumour.|
NB: A common presentation is premature adrenarche (pubic and/or axillary hair) in a child <7 years of age. In this case, if the X-ray of the left hand and wrist shows bone age maturity of >2 years above chronological age, request 17 OHP, DHEAS, androstenedione and testosterone to rule out late onset CAH as mentioned above.
Any other tests?
If the above tests don’t point in any particular direction, the next investigation would be a GnRH agonist stimulation test. It can be performed locally at most hospitals, but isn’t something you’d be requesting without discussing with a paediatric endocrinologist first. A GnRH agonist stimulation test is used for children who have normal LH/FSH levels, but have ongoing signs of puberty progressing.
Imaging is your next stop if blood results are abnormal, or if suggested after discussing with your consultant or paediatric endocrinologist.
- MRI brain to look for a central mass/abnormality.
- Pelvic USS for girls to assess for uterine and ovarian volume or ovarian cysts, and in boys to assess for a testicular tumour.
- Abdominal USS or CT scan if suspecting an adrenal tumour.
What to do next?
Get a paediatric endocrinologist involved early on in suspected precocious puberty. It’s important to investigate this promptly as early puberty will have a significant impact on adult height. Most cases will not need immediate investigations or actions in A&E/clinic. You have time – discuss, formulate a plan and bring back for blood tests and review.
And finally – what does a consultant endocrinologist want to know in a referral letter?
Duration of symptoms
Plot on a growth chart (ideally give previous height/weight if known)
Bone age assessment (if possible)
Reports of any imaging findings if performed
Dr Susannah Pye, written with consultant support from Dr Vaseem Hakeem