Glasgow Obstetrical & Gynaecological Society, 110th session

Minutes of the First Meeting of the 110th Session of the Glasgow Obstetrical and Gynaecological Society held in the Royal College of Physicians & Surgeons, St Vincent Street, Glasgow on 27thOctober 2010

The President, Dr Elaine Melrose, was in the chair.

Apologies were received from:

Drs Mathers, McNay, Kennedy, Thompson, Lumsden, Perera, McGough andHepburn.

Applications for membership were accepted for

Drs Veenu Tyagi , Linda McMillan,Anja Guttinger

It was intimated that Dr Stein Bjornsson was the proposed Vice President elect, to be confirmed at the AGM.

In attendance – 55.

A minutes’ silence was held following intimation of the death of 2 members, Dr Jim Cordiner and Dr Eddie Torbet

PRESENTATION

Dr Melrose reminded the society that the constitution from 1949said that the object of GOGS was to advance the knowledge of ‘obstetrics, gynaecolgy and pediatrics’, and she welcomed the speaker for the evening, Dr Malcolm Donaldson,Senior Lecturer in child health who talked to the society on ‘Pubertal Problems’.

Dr Donaldson informed the society that he would cover the following in his talk: normal puberty; sexual precocity; delayed and abnormal puberty in girls and optimal induction and maintenance of puberty in girls with Turner syndrome

He described the importance of the hypothalamo-pituitary-gonadal axis in ovarian development followed by a description of the physiology of puberty. Growth in puberty and final height is dependent upon oestrogen in both boys and girls.

Pubertal (Tanner) staging demonstrates the different pattern of puberty in boys and girls.

Dr Donaldson defined the following conditions:

  • sexual precocity - advanced sexual development regardless of type or cause
  • precocious puberty - true puberty occurring before 8 years in girls and 9 years in boys
  • early or advanced puberty - true puberty beginning between 8-10 years in girls and 9-11 years in boys
  • Precocious pseudopuberty/false precocious puberty– sexual precocity caused by abnormal secretion of sex steroids independently of the H-P-G axis

(Thelarche – breast development; pubarche – development of pubic hair; menarche – onset of periods; adrenarche – an adrenal event occurring between 6-8 years, with increase in secretion of the weak adrenal andogren DHAS)

Sexual Precocity

Investigation of sexual precocity in girls

•LHRH test to determine prepubertal (peak LH <5 U/l) or prepubertal response (NB sensitivity for detecting true puberty is 80-90%, not 100%!)

•Pelvic ultrasound

•Serum and urinary sex steroids if androgenic features present

•Serum oestradiol level and thyroid function

•MRI of brain if precocious puberty confirmed

Treatment of precocious puberty has been revolutionised with long acting GnRH analogues.

Exaggerated adrenarche

•Usually seen in girls aged 6-8 years with mild androgenicity

–greasy skin and hair

–body odour

–modest pubic and axillary hair development

•The girls are often overweight

•Virilising precocious pseudopuberty should be excluded; but this is usually clinically obvious (more severe virilisation)

•Modest increase in levels of androstenedione, DHAS, testosterone

Virilising precocious pseudopuberty

•Suggested by the scenario of virilising sexual precocity (enlargement of the clitoris, pubic/axillary hair, increase in growth rate) which is more marked than in EA

•Short history suggests a tumour (adrenal or ovarian)

•Prolonged history with tall stature evocative of simple virilising CAH

•Measure testosterone, androstènedione, 17-OHP & DHAS before and after synthetic ACTH stimulation, also urinary steroids, and imaging of adrenals and ovaries

Treat underlying cause e.g. surgical for tumours, medical for CAH

Delayed and abnormal puberty

•Delayed puberty: absence of secondary sexual development aged >13 years in girls and >14 years in boys

•Pubertal failure: failure of puberty to begin or, having begun, to complete

•Hypogondadism: impairment of the gonadal axis at hypothalamic (3°), pituitary (2°), or gonadal (1°)

Classification

•Central delay with an intact gonadal axis

•Central delay with impairment of the gonadal axis

•primary gonadal impairment/DSD

Central delay with intact H-P axis

•Constitutional delay in growth & adolescence (CDGA)

•Chronic systemic disease (e.g. inflammatory bowel disease)

•Poor nutrition (e.g. anorexia nervosa)

•Psychosocial deprivation

•Steroid therapy

Central delay with impaired H-P axis

Prenatal/genetic

•Congenital hypopituitarism

•GnRH/gonadotrophin deficiency (e.g. Kallmann’s syndrome, Prader-Willi syndrome)

Postnatal

•Tumours adjacent to H-P axis e.g. craniopharyngioma, optic glioma

•Irradiation e.g. for tumour in hypothalamo-pituitary region e.g. germinoma

•Surgery e.g. for craniopharyngioma

Incomplete / absent puberty due to primary ovarian failure or DSD

Prenatal

•Gonadal dysgenesis e.g. Turner syndrome, pure gonadal dysgenesis (46,XX or 46,XY)

•Complete androgen insensitivity syndrome

Postnatal

•Irradiation e.g. TBI +/- chemotherapy, cranio-spinal

•Galactosaemia

Clinical assessment of delayed puberty

•Growth pattern

•General health

•Systematic review if history suggests lack of energy, tiredness

•History of asthma

•Sense of smell (difficult!)

Past medical history

•Enquiry for past events making hypogonadism likely/certain e.g.

• - bilateral cryptorchidism

• - bilateral orchidopexy

• - gonadal irradiation or TBI

• - craniopharyngioma post surgery

•Features suggestive of Turner syndrome e.g middle ear disease, coarctation of aorta/aortic stenosis, horseshoe kidney

•Previous treatment with steroids, e.g. for asthma, nephrotic syndrome

Family history

•Family patterns of puberty: delayed menarche (>15 years) in mother and sisters, delayed adolescent growth spurt in father, brothers, and uncles

•History of relatives with history of genital surgery; infertility; amenorrhoea

Social and educational aspects

•School - attendance, performance, peer relationships, relationships with authority figures

•Sport - ability to participate in activities such as PE and football

•Leisure activities - music, drama, computer, partying

•Family situation

Examination

•General assessment

- affect, mood, well being

•Auxology

- height and weight

- measured parental heights

- pubertal staging

•Nutritional assessment

•Search for dysmorphic features

•Systemic examination

- Clubbing

- Cardiovascular assessment including femoral pulses, blood pressure)

- Examination of fundi for optic nerve atrophy

- Urinalysis

Diagnosis of delayed / incomplete puberty

•A clinical diagnosis can usually be made on the basis of the history and examination

•The need for investigation is determined by the clinical assessment

Optimal induction and maintenance of puberty in girls with Turner syndrome

Turners syndrome (XO)

•1 in 2,500 live female births

• High incidence of fetal loss (est. 97-99%)

Born each year:

• 12 girls in Scotland

• 155 girls in the UK

Living with TS at any one time:

• 2800 girls aged ≤18 years

6500 women aged 18-60 years

Features of TS

•Short Stature

•Ovarian dysgenesis

•Associated disorders: cardiac, renal, thyroid

•ENT problems

•Behavioural/psychosocial/educational difficulties

•Physical stigmata

Occupations – many professional and academic – no NEDS!

Treatment

•Short Stature

– Growth hormone (GH) therapy

– Oxandrolone therapy

•Ovarian dysgenesis

– Oestrogen therapy:

– When to start?

– What induction regime?

– What post-induction regime?

Aim of inducing and maintaining puberty

•To mimic physical & psychological changes which occur in natural puberty

•Development of secondary sexual characteristics & female identity

•Growth

•Cardiovascular health

•Reproductive health

•Bone health

•Cognitive health

Type of oestrogen – natural or synthetic – pros and cons.

When should puberty be induced? The Turner controversy – pros and cons of early and late treatment of both oxandrolone and oestrogen. The results of the Turner study 1 have been submitted to BMJ for publication.

Take home messages

•Oxandrolone from 9 years of age increases final height in girls with TS receiving a standard dose of growth hormone therapy

•Inducing puberty with oral Ethinylestradiol from 14 years, rather than 12 years of age increases final height in girls with TS

•However, these effects are not additive i.e. there is no benefit of doing both

•Oxandrolone is a realistic alternative to delaying pubertal induction in girls with TS

Research proposal for post Uk I trial (II) - Effect of transdermal versus oral oestrogen replacement on cardiovascular, skeletal and uterine health in girls with Turner syndrome aged 12-18 years and trial III maintenance therapy submitted to HTA but rejected on basis that too few patients affected and not ill enough to merit £1.2 million research grant. Possible solutions to funding impasse include reduction in costs, ring fence funding or compartmentalise funding.

Throughout his talk, Dr Donaldson gave examples of clinical cases and different scenarios and emphasised the importance of asking the right questions to reach the correct diagnosis, noting that these cases are quite uncommon and early referral to Yorkhill is recommended.

There followed several questions and comments from the floor.

The vote of thanks was given by Dr Melrose.

AOCB

Dr Melrose thanked Pfizerand Leo for their generous sponsorship.

Members of the society were reminded that the next meeting will take place at RCPSG on 17th November 2010 when will Prof Brocklehurst will address the society.

…………………………………………………President