Disorders of Growth

and Development
PROFESSOR JOSANNE VASSALLO
MD YR III ENDOCRINOLOGY MODULE
Definition
 Short stature: children lying below the 3rd
centile on standardised growth curves after
matching for age and sex

 Tall stature: children who are persistently above

the 97 centile for age and sex on standardised
growth curves
Growth Chart
Factors regulating growth

Genetic
Environmental
Hormonal
Unknown
Aetiology

 Intrinsic shortness
 Delayed growth
 Attenuated growth
 Accelerated growth but early
epiphyseal closure
Management

History
Examination
Investigation
Treatment
History

 Time course
In utero
1st year of life
After 1st year
 Symptoms

Lethargy
Wt gain or loss
Apetite
Bowel habits
Developmental/neurological problems
Headaches
Visual problems
History - II
 PMH
 Meningitis,
Trauma
NG, Radiotherapy, Chemotherapy
Surgery
Diabetes Mellitus
 Drug history
 Social History
 Family History
Examination

 Height
 Weight
 Arm span
 Upper lower ratio
 Skin
 CVS, RS, Abdo exam
 CNS esp fundi, visual fields, reflexes
 Stage of pubertal development
Arm span measurement
Stages of Puberty
Investigation

 CBC, ESR
 U&M, U&E creatinine
 Blood glucose
 LFTs
 Calcium, phosphate, albumen
 Coeliac screen/GI studies
 Karyotype
Investigation - II

 Hormonal profile
 GH
 IGF-I
 Testosterone/estradiol
 Cortisol
 TFTs
 Prolactin
 Vit D/ PTH
Investigation - III

 Dynamic function testing

 Glucagon stimulation test
 Insulin Tolerance Test
 RH stimulation tests (GnRH, TRH, CRH, GHRH)
 OGTT for GH suppression in instances of tall stature

 Imaging
 Bone age
 Skeletal survey
 Hypothalamic/pituitary assessment - MRI
Insulin Tolerance Test
GH (mU/L) , Glucose

10
(mmol/L)

5 Glucose
10

0 0

1 2 3 4 5 6
1 2 3 4 5 6
Time (Hrs)

Time (Hrs)
Treatment
 Nutritionand exercise
 Medication
 GH/IGF-I
 Thyroxine
 Hydrocortisone/Prednisolone
 Insulin
 Vit
D and calcium
 GnRH antagonisits

 Surgery
 Craniopharyngioma
 Pitutiary Adenoma
 Correction of skeletal deformity
Female Reproductive
Physiology
Hypothalamic-pituitary-
ovarian axis
Ovarian and uterine cylces.
Male Reproductive
Physiology
Hypothalamic-pituitary-
testicular axis
Steroid Levels with Age
Adrenal-Ovarian
Steroidogenesis
Pathophysiology of male and
female reproductive dysfunction - I

 Hormone deficiency
 Homone excess
 Primary
 Primary
 Hypogonadism
 PCOS
 Menopause
 Granulosa cell tumour
 Turner syndrome
 Leydig cell tumour
 Klinefelter syndrome
 Teratoma

 Secondary
 Secondary
 Hypopituitarism
 Pituitary
gonadotropinoma  Kallmann syndrome
 Systemic illness incl AN
Pathophysiology of male and
female reproductive dysfunction -
II
 Hormone
hypersensitivity
 Idiopathic hirsutism
 Hormone resistance
 Androgen resistance
syndrome
 Complete testicular
feminization
 Partial testicular
feminsisation
 5 alpha reductase
deficiency
Hypogonadism
PRIMARY (HYPERGONADOTROPIC) HYPOGONADISM

SECONDARY (HYPOGONADOTROPIC) HYPOGONADISM

Aetiology of delayed puberty and
hypogonadism
 Constitutional delay
 Hypogonadotropic hypogonadism
 Structural hypothalamic or pituitary disease
 Functional gonadotrophin deficiency
 Isolated gonadotrophin deficiency – eg Kallmann s
syndrome
 Hypergonadotropic hypogonadism
 Acquired gonadal damage
 Developmental congenital disorders
Presentation
of Hypogonadism
 Delayed puberty
 Primary/secondary amenorrhoea
 Primary/secondary azo-/oligozoospermia
 Loss of libido
 Loss of secondary sex characteristics
 Erectile dysfunction
 Infertility
 Osteoporosis
History

General
Developmental
Menstrual Activity
Sexual History
Examination
General – Ht, Wt, Armspan
Secondary sex characteristics
Skin - Hair, oiliness, pallor,
pigmentation
Eyes – visual fields
Breasts – gynaecomastia
Genitalia – external and internal
Investigation

Hormone profiles
CBC, Biochemical profile, PSA
Karyotyping
Imaging - US, MRI
Laparoscopy/Biopsy
Management
Considerations

Induction of puberty

Hormone Replacement

Ovulation/Spermatogenesis
Induction
 Precocius Puberty

PUBERTAL DEVELOPMENT OCCURRING BEFORE THE AGE

OF 9 IN BOYS AND BEFORE THE AGE OF 6-8 YEARS IN GIRLS
Causes of True vs Pseudo
Precocious Puberty
 Congenital CNS structural abnormalities
 Central Nervous system tumours
 Hypothalamic hamartomas
 Astrocytomas
 Germ cell tumours
 CNS injury
 Infection
 Inflammation
 Trauma
 Surgery
NB Pseudoprecocius puberty eg due to Congenital Adrenal
Hyperplasia and McCune Albright Syndrome
Treatment options

 Treatment of the underlying

pathology
 GnRH analogs for pubertal arrest
till development is age appropriate
Polycystic Ovarian
Syndrome
Polycystic Ovarian
Syndrome
 Irregular periods
 Hirsutism
 Acne
 LH:FSH ratio > 2
 Enlarged or polycystic ovaries
 Obesity
 Insulin Resistance Syndrome (incl IGT, DM,
hyperlipidaemia, hypertension)
Therapeutic targets
 Control of skin problems
 TopicalRx of acne and hair removal
 OCP, steroids, antiandrogens

 Control of cycles
 OCP, steroids
 Rx of subfertility/infertility
 As for hypogonadism
 Control of metabolic problems
 Insulin sensitisers
Conclusion
 Ensure adequate supply of appropriate
medications
 Monitor compliance (interview & analysis)
 Monitor response to treatment
 Suggest early consultation with physician if
neglecting appointments
 Watch out for side effects/adverse events
Congenital Adrenal
Hyperplasia
Adrenal Cortical Physiology
Congenital Adrenal
Hyperplasia

Hydrocortisone twice daily

to suppress ACTH secretion
Reverse Prednisolone
Patient Education
 Focuson
Medical condition
Importance of replacement
Need to step up replacement at times of
surgery, pregnancy etc
Effects of under- and over-replacement

 Patient support groups

 “Helpline”
Follow-Up
 Monitoring re “side effects” of replacement
 Steroids:weight gain, skin changes,
hirsutism, BP, DM, osteoporosis

 Estrogens/Progesterone, Testosterone:
wt
gain, mood swings, headaches, NG breast,
uterus, prostate
Hormone resistance
syndromes
Gonadal and Phenotypic
Sexual Differentiation
Androgen- Receptor
interactions

Meehan et al Front Biosci.

2003 May 1;8:d780-800
Androgen Resistance
Management

 Multidisciplinary Approach
 Psychological Assessment
 Gender Assignment
 Gender Maintenance
Surgery
HRT
Thank you