Precocious Pubertycase reviews Nadia Muhi Iddin Endocrinology PLEAT Conquest hospital 8/7/2011
Case 1 • Term baby. Born locally. 2.8Kg • Primigaravida 18 year old mother. • Uneventful pregnancy and delivery. • No significant medical history. • Family now had a 4 month old baby at time of child referral to paediatric services.
3/2008 • GP referral at 3.5 year with 2 month history of breast development and rapid growth. • Seen with in a month. Had single episode of vaginal bleeding & abdominal pain. • No headache or visual symptoms. • Past history of mild eczema. • Breast stage B3 bilateral. No pubic or axillary hair growth. Family thought is was ( puppy fat) • Height & weight 98th centile (2002 growth chart) • Child now had 2 younger siblings 2 year old sister and 7 month old brother.
Investigations • TFT,FSH, LH, 17B oestardiol. • Urgent MRI Head/Pituitary with gadolinium under GA. • Urine steroid profile. • FBC, LFT, Ca Profile, U&E, creatinine, Bicarbonate, Iron levels. • Bone age ( left hand & wrist) • Pelvic and renal US.
management • Diagnosis of Gonadotropin dependant central precocious puberty. • Discussion with paediatric endocrinologist & parents and maternal grandfather. • Discussion with pharmacy for medication. • Managements included Cryptoterone acetate 50mg tablet. • IM injections at hospital. Gonapeptyl depot 3.75mg ( Triptorelin) 6/5/2008. • Further vaginal bleed. • 4 weeks interval. Commenced on Decapeptyl SR 11.25mg Tritorelin IM injection on 12 week interval. • Local appointment with paediatric endocrinologist 1/7/2008. • Offer of referral to CAHMS. • Home care nursing team for the injections.
Follow up • 1/2009. Injection interval reduced to 11 weeks. Becomes moody before injections. • Illness 9/2009 reduced energy . • Mother coping with appointments and 3 young children. • Started reception year and school support at home. ( play therapy) • 7/2009 reduced to 9 weeks interval. LH.FSH not completely suppressed. • 2/2010 reduced to 8 week interval. Mother & child happy.
Continued • 4/2010 family disruption and lost appointment. Moved with grandparents • 3/2010 product change needles. • 2/2010 repeat bone age. • Follow up 6 monthly and annual with endocrinologist. • No concerns started ballet. Went on holiday.
Case 2 • Term female baby Born at the Conquest. • 3425 gm birth weight. 11/2005 • Admitted at 5 weeks for RSV Bronchiolitis. • Admitted at 10 weeks with croup. • Admitted at 11 moths swallowed a dishwasher calgon tablet. • Presented at 2years 5months because of rapid Growth in the last year. HV referral.
History • Always big baby with length near 91 centile. • Parents tall mid parental height 91st centile-98th. • Currently in 5-6 year old cloths. • Older brother of 7 years and a shorter 5 year old brother. • Current height and weight above 99.8th centile. • Grown 4.8cm in 4 months. • HV referral.
Examination • Pubic hair stage 2 • Breast stage 3 • Body odour • White vaginal discharge. • No headaches, visual symptoms, faints or fits.
Investigations • FBC,LFT,U&E, Creatinine. Bicarbonate. • Ca profile and protein • TFT,LH,FSH,IGF1,oestardiol. Prolactine • Tumour markers AFP, Serum B HCG • Bone age • MRI head under GA • Pelvic & renal US.
Management • At age 2 years and 9 months. 8/2008 • Treptoreline ( Gonapeptyl) IM injection. • Oral Crypriterone acetate. • Followed in 4 weeks . • Meetings with family and printed information. Contact with nurse team. • Blood stained discharge 9/2008.
Other investigations • Presenting IGF1:47.3 (4-20) • Presenting IGFBP3: 3.4 (0.4-2.9) • Prolactin:1842mU/L. Repeat test 190mU/L • Urine steroid profile qualitatively normal. • Pelvic US was difficult but reported both ovaries mature with follicles. Left 22mmX15mmUterus mature.
Progress • 10/2008 Blood stained vaginal discharge. • Mother concern about appetite. • 3/2009 Reduced injections to every 10 weeks. • 11/2009 Mood changes 1 week before medication. • 1/2010 technical difficulties revert to 4 weekly medication. Stress. • 1/2011 Unwell for 3 weeks unrelated illness. • 6 monthly and annual follow up. Growth and endocrine.
Precocious Puberty • True precocity refers to an abnormally early puberty in which physical changes follow a normal progression and lead to full sexual maturity. • Age below 8 years in girls and 9 in boys. • Variant under age 6 in girls and under 8 for menarche. • Partial forms of precocious puberty.
McCune-Albright syndrome Primary hypothyroidism. Long standing Exogenous sex steroid exposure. Partial forms of Precocious Puberty Premature thelarche Premature adrenarche Premature isolated menarche. The 1st 2 are much more common. Incomplete/LHRL in both sexes
McCune –Albright syndrome • Irregular skin pigmentation • Fibrous bone dysplasia • Endocrine autonomy of glands notably ovaries. • Very enlarged ovaries with solitary cysts • Precocious puberty with early vaginal bleeding. • *Gene map locus 20q13.2 • Bone fractures Ref: Geneva foundation for medical education& research.
Premature thelarche • Infant or young girl • Transient/ Cyclical • Often asymmetrical • No growth acceleration or other pubertal features. • Parallel follicular development but uterus remains small. • Self limiting but may progress to early puberty.
Premature adrenache /Pubarche • Normal mid childhood 6-8 years increase in adrenal androgens due to maturation of Zona reticularis. • Modest growth spurt. • Early pubic hair • Advanced bone age. • More common in girls • If before age 6 or increasing exclude CAH and adrenal tumours.
Detailed examination in girls under 6 years Abnormal sequence or virilisation in girls. Neurological symptoms, hypertension or abnormal growth. Testicular palpation in boys. Guide to examination
Issues to consider • Explanation. 90% Ideopathic in girls. • Support. Child. Family and school • Suppressing medications. GnRh analogues • Monitoring of growth. Rate and puberty. • Bone age. • Monitoring of hormonal levels. • Final height. • Side effects of medication.
Treatment requires specialist management • Gonadotropin depend precocious puberty :Gonadorelin analogues Aim: • Delay development of secondary sex characteristics • Reduce growth velocity Gonadotropin Independent precocious puberty. • Crypterone is a progesterone with anti-androgen activity used in gonodotropine independent Precocious Puberty/ • Testolactone • Spironolactone.
Gonadorelin analogues • Goserelin. Not licensed for use in children. Implant 2 manufacturers. • Leuprorelin acetate.Not licensed for use in children. 1 manufacturer. ( 4 & 12 week) Subcutaneous or IM injection. • Triptorelin: Sub cut or im 3-4 weekly. ( Gonapeptyl) IM every 3 months ( Decapeptyl SR). Side effects: Local, GI, asthenia, arthralgia . • Other products licensed in USA. Products under trial.
Behavioural interventions • Peer relationships in school/tall stature. • Adults raised expectations. • No evidence of long term psychological sequel. • Protection from inappropriate relationships • Patient education. • Play therapy & or psychology referral for child and family with significant issues.
References • Hospital paediatrics: A.Milner/D.Hull • Nelson text book of pediatrics:18th Edition • BNF for children2010-2011. • Paediatrics. Clinical guide for nurse practitioners. • Essential paediatrics: David Hull