Adolescent gynae

Question 1

Primary Amenorrhea

Answer 1

No menstruation by the age of 16 in the presence of normal secondary sexual characteristics or 14 in the absence of puberty.

Question 2

Investigations of Primary Amenorrhea

Answer 2

• bHCG
• FBC
• LH, FSH, oestradiol, progesterone
• Prolactin
• TSH and T4
• Serum 17-OHP
• Serum testosterone, sex binding globulin
• DHEAs
• Karyotype
• Pelvic USS +/- MRI
• Bone age X-rays
• Autoimmune screen

Question 3

common causes of primary amenorrhea

Answer 3

Gonadal dysgenesis (43%) (including turner's syndrome, premature ovarian insufficiency, 46XY gonadal dysgenesis)
Mullerian agenesis (15%)
Constitutional (14%)
PCOS (7%)
Isolated GnRH deficiency (5%)
Transverse vaginal septum (3%)
Weight loss/anorexia (2%) 
Hypopituitarism (2%)

Question 4

CAIS - 46XY and ambiguous gentialia

Answer 4

The gonads are testes and produce hormones as per typical male AMH, DHT and testosterone. Androgen receptors within the body are not able to respond to circulating androgens.

AMH produced by the testes still results in regression of the Mullerian ducts and the individual therefore has external female phenotype and male internal gonads.

At puberty increasing levels of testosterone converts peripherally into oestrogen, resulting in female development of secondary sexual characteristics.

Due to regression of Mullerian ducts there is no uterus or upper vagina.

Question 5

Management points of CAIS/pure gonadal dysgenesis

Answer 5

Germ Cell Tumour
Gonadectomy in early adulthood

Gender dysmorphia and mental health issues surrounding diagnosis
Psychological support

Infertility
IVF with donor oocyte and surrogate

Short vaginal length causing sexual dysfunction Vaginal creation with dilators

Increased Cardiovascular disease risk and lower bone density once gonads have been removed HRT until 52 years old

Question 6

MRKH syndrome: 46XX

Answer 6

Failure of the uterus and the vagina to develop properly in women who have normal ovarian function and normal external genitalia.

Women develop normal secondary sexual characteristics during puberty (e.g., breast development and pubic hair), but do not have a menstrual cycle (primary amenorrhea).

Can occur with abnormalities of additional organ systems including mainly the kidneys and the skeleton.

Question 7

Causes of primary ovarian insufficiency:

Answer 7

Autoimmune premature ovarian failure
Infection e.g. mumps or HIV
Surgical removal of ovaries 
Chemotherapy or radiotherapy. 
Genetic condition
No cause identified in up to 2/3 of cases.

Question 8

Risks with POI

Answer 8

MDT approach – paed endocrinologist, psych, fertility
Address psychological distress and refer to support services
Discuss puberty induction with HRT
Discuss bone health and impact on long term cardiovascular health
Discuss additional investigations needed – pregnancy test, consider CMV/mumps screen
Discuss long term fertility implications
Discuss sexual function and contraception %% ovulate
Discuss genetic implications – may be X chromosome deletion, may be relevant for sister to get tested

Question 9

Pregnancy risks with rudimentary horn

Answer 9

Surgical risks

Preterm birth- decreased cavity size

Malpresentation- shape of cavity, size

Fetal growth restriction- small cavity, abnormal uterine vascularisation

Caesarean section- malpresentation, placental insufficiency

Miscarriage/ectopic- implantation may occur in an abnormal area or on the surgical scar

HTN- increased risk due to single kidney

Question 10

Pediatric Vulvovaginitis

Answer 10

Provide hygiene advice
Recommend wiping front to back when toileting
Avoid irritants such as soap when showering
Clean vulval area with clean hand and water only
Wear loose cotton underwear rather than tight synthetic clothing
Reassure family that symptoms will resolve with puberty and there will be no long term sequelae
As symptomatic local estrogen cream could be applied for up to six weeks , parents should be advised that due to some systemic absorption some vaginal spotting and breast swelling can occur.
If a pathogen is isolated on vaginal swab treat with appropriate antibiotic

Question 11

Causes of precocious puberty

Answer 11

Central (80%) - ordered as per normal puberty
 Idiopathic (75%)
 Central Nervous System Lesions
 Excess sex steroid exposure
 Pituitary Gonadotrophin Secreting Tumours
 Specific Gene Mutations
Peripheral (20%) – always pathological. disordered.
 Hormone producing ovarian tumours or cysts
 Exogenous administration of oestrogen
 McCune Albright Syndrom

Question 12

Treatment precocious puberty

Answer 12

Treatment is usually led by a paediatric endocrinologist to slow growth to that of the peers until age 10 - 11 years of age and avoid early skeletal maturation and secondary sexual characteristics.
 Pubertal development may be suppressed by GnrH analogue (Zoladex) and continue till 10-11 to allow puberty to progress normally
 Require 3 - 6 monthly clinical assessment and annual bone density assessment

Discuss
 Recommend head MRI (always if under age 6 or if neurological signs/symptoms)
 Referral to paediatric endocrinologist

o SE of GnRH: headache, mood change, rash, local irritation, PVB due to oestrogen withdrawal
 Support/counselling for girl/family

Question 13

HEEADSSS Assessment

Answer 13

Home life - family and stability
Education and employment
Eating and exercise
Activities and peer relationships
Drug use/smoking/alcohol
Sexuality
Suicide/self-harm
Safety - risk taking behaviour

Question 14

History in precocious puberty

Answer 14

· Age of onset of symptoms – does it truly meet the criteria?
· Rate of progression of secondary sex characteristics – rapid progression is associated with earlier fusion of the growth plates and reduced adult height. It would be an indication for more rapid intervention
· Any neurological symptoms – e.g. visual field changes or upper motor symptoms that would suggest a central nervous system cause
· Any family history of precocious or early puberty – would suggest a genetic or idiopathic cause
· Any history of exogenous steroid administration – for example to treat severe asthma or autoimmune disease when younger
· History of abdominal pain, bloating etc. – may be suggestive of ovarian tumour/cyst
· Assessment of psychological well-being – girls going through precocious puberty are more likely to have endured bullying and harassment. Questions should include ones about mood, thoughts of self-harm and/or suicide

Question 15

Examination in precocious puberty

Answer 15

· Baseline height and weight on age specific charts– girls going through progressive precocious puberty are likely to be much taller than their peers and their height velocity is likely to be higher too
· Assessment of secondary sexual characteristics – the Tanner staging for breast and pubic hair development can be helpful in this assessment
· Comprehensive neurological exam for both the cranial and peripheral nerves, to elicit any signs of a central nervous system lesion
· Examine the skin for neurofibromatosis or café au lait spots (suggestive of McCune Albright syndrome)

Question 16

Swyer’s syndrome - 46, XY complete gonadal dysgenesis

Answer 16

Swyer syndrome is a rare disorder characterized by the failure of the sex glands (i.e., testicles or ovaries) to develop. Swyer syndrome is classified as a disorder of sex development (DSD), which encompasses any disorder in which chromosomal, gondal or anatomic sex development is abnormal.
A diagnosis of Swyer syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings (e.g., no periods, streak gonads) and a variety of tests including chromosomal analysis.
MAy be useful to test immediate family
This is a condition where there is gonadal dysgenesis – failure of development of male testes due to mutation of SRY gene on Y chromosome.
As a result: No T or AMH produced by testes
No regression of MD structures so internally and externally female genitalia – uterus, FT and Vagina.

Question 17

Turner’s syndrome

Answer 17

Turner syndrome, a condition that affects only females, results when one of the X chromosomes (sex chromosomes) is missing or partially missing.
Prevalence 1:2500-3000 live female births. Most common chromosomal disorder in females. 46XO.
Premature gonadal failure characterised by increased follicular destruction.
Features:
Wide or weblike neck
Low-set ears
Broad chest with widely spaced nipples
Primary amenorrhea
Short stature
The risk of congenital heart defects such as bicuspid aortic valves, aortic coarctation, other valve abnormalities, and septal defect is increased.
Issues Turners Syndrome: 
- Cardiac issues  
- HTN – regular BP monitoring 
- Osteoporosis 
- Diabetes – HbA1c every year 
- Renal problems – renal function blood test every year 
- Depression/mental illness 
- Fertility
List screening tests at time of diagnosis of Turners syndrome:  
- Cardiovascular evaluation  
- Renal USS  
- Audiology assessment  
- Lipid profile  
- Thyroid function  
- HbA1c 
Spontaneous puberty may occur in

Question 18

Fertility and Turner’s

Answer 18

Preconception ECHO (within two years of planned pregnancy/ART)
Aortic root dissection >2.5 considered contraindication to pregnancy as peripartum risk of death 2%
Advise most women with Turner syndrome are infertile because of ovarian follicular depletion however spontaneous pregnancies are occasionally seen (~5%)
High risk of adverse pregnancy outcomes – miscarriage, severe IUGR, PET
Think of maternal renal and cardiac complications
Options
- ART:
IVF (with donor oocyte) pregnancy rates considerably better than IVF with autologous oocytes
vs
IVF with autologous oocytes (if menstruating as indicates some ovarian function however significantly lower pregnancy rates)
- Adoption
- Surrogacy

Question 19

Puberty induction

Answer 19

Start estrogen only HRT until menstruates then commence cyclical progesterone for endometrial protection - transdermal oestrogen followed by oral progestin.
Maintenance HRT until 51 years old for prevention of cardiovascular disease and osteoporosis.
Other ways to prevent osteoporosis: healthy BMI, weight bearing exercise, calcium and vit D, avoid excessive alcohol intake and smoking, bisphosphonates, FRAX and DEXA scans.
Can be maintained on COCP or low dose combined HRT

Question 20

A progesterone challenge

Answer 20

The progesterone challenge test is done by giving oral medroxyprogesterone acetate (Provera) 10 mg daily for 7-10 days. A positive response is any bleeding more than light spotting that occurs within 2 weeks after the progestin is given.

Question 21

Surgery in unicornuate uterus

Answer 21

Laparoscopic removal of rudimentary horn
Removal is often the safest management and is indicated if the woman is symptomatic. Also with functional endometrium in this horn the risk would be of a pregnancy occurring here which could result in rupture of the horn

Hysteroscopic procedure to open a passage between the rudimentary horn and the functional horn if feasible, would depend on location and proximity of rudimentary horn
Less morbidity and would result in improvement in monthly symptoms as haematocolpos would not occur if blood could freely drain. There would be residual risk of pregnancy occurring in this horn.

Question 22

Gynae malignancy
Germ cell tumours
From primitive germ cells before sexual differentiation has occurred.

Answer 22

Dysgerminoma - peak incidence 10-30yo
Tumour marker LDH
Rapid growth most 10cm tumours at diagnosis
Bilateral in 15%
75% present at stage 1
Surgery: unilateral salpingo-oophrectomy, peritoneal cytology and removal of retroperitoneal lymph nodes
If over stage 1a for chemo Bleomycin, etopiside and cisplatin.
Careful follow up 15-20% reoccur

Immature teratoma 1% of all dermoids
Occurs typically in first 2 decades of life
Surgery with chemo Bleomycin, etopiside and cisplatin if over stage 1a
Tumour marker inhibin
Follow up 3 monthly 2 years and 6 monthly for 3 years

Question 23

Rudimentary uterine horn

Answer 23

found in 74% of unicornuate uterus
Can be communicating or non communicating (94%)
usually present with dysmennorhoea
36% associated with renal anomaly
Recommend surgical removal of non communicating horns prior to child bearing due to preganncy and rupture risk

Question 24

Ambiguous genitalia

Answer 24

MDT: peadiatric endocrine, gynae, peads surgery and pyschologist.
Postpone gender assignment answer usually available in 3 days
May be significant gender identity issues and dis-satisfaction later in life

History:
- Pregnancy history
- Drugs taken in pregnancy
- Maternal virilisation
- Family history of consanguinity 
- Other inter-sex or sudden infant death
Examination:
- Vital signs and hydration
- Dysmorphic features
- midline defects (HPO)
- Jaundice (thyroid/cortisol issue)
- Examine external genitalia
Investigations:
- Monitor weight, fluid balance and electrolytes and glucose
- Hormones including AMH
- KArrotype and micro-array
- USS/MRI
- urogential sinogram