Endocrinology Flashcards
What is precocious puberty defined as?
Girls = breast development age <8yo
Boys = testicular development >4mL, age <9yo
What staging system is used for female breast development>
Tanner’s 5 breast development stages
What staging system is used for males testicular development?
Prader’s orchidometer
thelarche
breast development
Causes of precocious puberty
Gonadotrophin-Dependant Precocious Puberty [GDPP]
Gonadotrophin-Independent Precocious Puberty [GIPP] – 20% of PP
Benign isolated precocious puberty – these are all generally self-limiting
What causes gonadotrophin-dependent precocious puberty (GDPP)? Give examples
Premature activation of HPG axis
Idiopathic (no cause found in 80% girls and 40% boys)
CNS abnormalities (tumours, trauma, central congenital disorders
What causes gonadotrophin-independent precocious puberty (GIPP)? Give examples
Early puberty from increased gonadal activation independent of HPG
Ovarian – follicular cyst, granulosa cell tumour, Leydig cell tumour, gonadoblastoma
Testicular – Leydig cell tumour, testotoxicosis (defective LH-R function; a familial GIPP)
Adrenal – CAH, Cushing’s syndrome
Tumours – b-hCG-secreting tumour of liver, tumours of ovary, testes, adrenals
McCune-Albright syndrome – a multiple endocrinopathy of thyrotoxicosis, Cushing’s, acromegaly
S/S: polyostotic fibrous dysplasia, café-au-lait spots, ovarian cysts
Exogenous hormones – COCP, testosterone gels
CNS abnormalities that can cause Gonadotrophin-Dependant Precocious Puberty [GDPP]
tumours, trauma, central congenital disorders
Most common cause of Gonadotrophin-Dependant Precocious Puberty [GDPP]
Idiopathic (no cause found in 80% girls and 40% boys)
Ovarian abnormalities that can Gonadotrophin-Independent Precocious Puberty [GIPP]
follicular cyst, granulosa cell tumour, Leydig cell tumour, gonadoblastoma
Testicular abnormalities that can cause Gonadotrophin-Independent Precocious Puberty [GIPP]
Leydig cell tumour, testotoxicosis (defective LH-R function; a familial GIPP)
Adrenal causes of Gonadotrophin-Independent Precocious Puberty [GIPP]
CAH, Cushing’s syndrome
Tumours that can cause Gonadotrophin-Independent Precocious Puberty [GIPP]
b-hCG-secreting tumour of liver, tumours of ovary, testes, adrenals
What is McCune-albright syndrome? What can it cause?
a multiple endocrinopathy of thyrotoxicosis, Cushing’s, acromegaly
Gonadotrophin-Independent Precocious Puberty [GIPP]
Signs + Sx of McCune Albright Syndrome
polyostotic fibrous dysplasia, café-au-lait spots, ovarian cysts
NOTE: Cause of Gonadotrophin-Independent Precocious Puberty [GIPP]
Causes of benign isolated precocious puberty
Premature thelarche [isolated breast development before 8yo; normally between 6m and 2yo
Premature pubarche/adrenarche [isolated pubic hair development before 8yo (girls) or 9yo (boys)]:
Premature menarche [isolated vaginal bleeding before 8yo]
Investigations for precocious puberty
GnRH stimulation test (Gold Standard)
FSH, LH low = GIPP
FSH, LH high = GDPP
Wrist XR (non-dominant) for skeletal age
General hormone profile basal LH/FSH, serum testosterone and oestrogen
Urinary 17-OH progesterone if CAH suspected
Gold standard investigation for precocious puberty
GnRH stimulation test (Gold Standard)
FSH, LH low = GIPP
FSH, LH high = GDPP
What investigation done if CAH suspected?
Urinary 17-OH progesterone if CAH suspected
What additional investigation may be done in precocious puberty in females?
Pelvic USS
Which gender usually has an organic cause for precocious puberty?
Males - most likely has an organic cause
Females - not normally of concern
What additional investigation would be done in a male with precocious puberty?
Prader’s orchidometer measurement and examination of testes
Findings on testicular examination in someone with precocious puberty
Bilateral enlargement → GDPP (intracranial lesion –> MRI)
Unilateral enlargement→ gonadal tumour
Small testes → tumour or CAH (adrenal cause)
Bilateral testicular enlargement and precocious puberty
Bilateral enlargement → GDPP (intracranial lesion –> MRI)
Unilateral testicular enlargement and precocious puberty
Unilateral enlargement→ gonadal tumour
small testes and precocious puberty
tumour or CAH (adrenal cause)
Management of all types of precocious puberty
REFER TO PAEDIATRIC ENDOCRINOLOGIST
Management of GDPP with no underlying pathology
often no treatment is required
Management of GDPP
GnRH agonist (e.g. leuprolide) + GH therapy
GnRH agonist + cryproterone (anti-androgen)
Management of GIPP
McCune Albright or Testotoxicosis: 1st: ketoconazole or cyproterone; 2nd: aromatase inhibitors
CAH: hydrocortisone + GnRH agonist
Management of McCune Albright (Type of GIPP)
1st: ketoconazole or cyproterone; 2nd: aromatase inhibitors
Management of Testotoxicosis (Type of GIPP)
1st: ketoconazole or cyproterone; 2nd: aromatase inhibitors
Management of CAH (Type of GIPP)
CAH: hydrocortisone + GnRH agonist
What is the most common non-iatrogenic cause of low cortisol?
Congenital adrenal hyperplasia
What enzyme is deficient in 90% of patients with CAH?
21-hydroxylase enzyme
What genetic inheritance is seen in CAH?
Autosomal recessive
Presentation of CAH
Virilisation of external genetalia
Female infants –> clitoromegaly, fusion of labia
Male infants –> enlarged penis and scrotum pigmented [much harder to see]
Salt-losing crisis [often the 1st sign in boys]
Week 1 to 3 of age – more common in boys (in girls, virilisation is noted early and CAH treated)
Vomiting, WL, hypotonia, circulatory collapse
Tall stature
Excess androgens –> muscular build, adult body odour, pubic hair, acne
What is often the 1st sign of CAH in boys?
Salt losing crisis
What is often the 1st sign of CAH in girls?
Virilisation of external genitalia
Is CAH often identified earlier in males or females?
Females, virilisation is noted early and CAH treated
How does virilisation of external genitalia present in females?
clitoromegaly, fusion of labia
How does virilisation of external genitalia present in males?
enlarged penis and scrotum pigmented [much harder to see]
Investigations in CAH
Initial (ambiguous genitalia, no external gonads) –> USS [examine internal genitalia]
Confirmatory (CAH) –> raised plasma 17a-hydroxyprogesterone (cannot do in a newborn)
Biochemical abnormalities [FBC]:
Salt-losing crisis –> low sodium, high potassium
Metabolic acidosis –> low bicarbonate
Hypoglycaemia –> low glucose from low cortisol
Initial investigation for CAH
Initial (ambiguous genitalia, no external gonads) –> USS [examine internal genitalia]
Confirmatory investigation of CAH
Confirmatory (CAH) –> raised plasma 17a-hydroxyprogesterone (cannot do in a newborn)
Biochemical abnormalities in CAH
Salt-losing crisis –> low sodium, high potassium
Metabolic acidosis –> low bicarbonate
Hypoglycaemia –> low glucose from low cortisol
What causes the low sodium, high potassium picture in CAH?
No aldosterone
What test in CAH can you not do in a newborn? What test to do instead?
raised plasma 17a-hydroxyprogesterone
Do USS [examine internal genitalia] instead
Table showing presentations of adrenal insufficiency
Management of CAH
Corrective surgery – for affected females on the external genitalia
Long-term management:
Life-long glucocorticoids (hydrocortisone) to suppress ACTH levels (and hence testosterone)
Mineralocorticoids (fludrocortisone) if there is salt loss
Salt-losing crisis –> IV hydrocortisone, IV saline, IV dextrose
Who is corrective surgery offered to in CAH?
affected females on the external genitalia
NOTE: Girls are raised as girls (they have a uterus and ovaries)
Definitive surgery often delayed until early puberty
What is the long term management of CAH
Life-long glucocorticoids (hydrocortisone) to suppress ACTH levels (and hence testosterone)
Mineralocorticoids (fludrocortisone) if there is salt loss
Sick day rules for management of CAH
Double hydrocortisone
How is salt losing crisis managed in CAH?
IV hydrocortisone, IV saline, IV dextrose
What is androgen insensitivity syndrome?
Delayed puberty in a ‘girl’ with bilateral groin swellings are undescended testicles
What are the bilateral groin swellings in androgen insensitivity?
undescended testicles
Genotype and phenotype in androgen insensitivity syndrome
genotype = XY; phenotype = XX
Two types of androgen insensitivity syndrome
Complete androgen insensitivity syndrome (CAIS)
Partial androgen insensitivity syndrome (PAIS)
How does complete androgen insensitivity syndrome (CAIS) present?
testosterone has no effect; genitals are entirely female
How does partial androgen insensitivity syndrome (PAIS) present?
testosterone has some effect; genitals are often more ambiguous
Presentation of androgen insensitivity syndrome
Ambiguous genitalia from birth
(CAIS will look more like female genitalia; PAIS may vary)
Undescended testicles (bilateral groin swelling)
Often diagnosed at puberty:
Girl with CAIS will develop breasts, may be slightly taller than usual
Not have periods
Little/no pubic hair
Investigations for androgen insensitivity syndrome
Examination: abdomen, genitals
Bloods: oestrogen/progesterone, testosterone
Karyotype
Management of androgen insensitivity syndrome
MDT needed
Counselling
Surgery
E.g. removing undescended testicles; vaginal dilatation
E.g. breast reduction surgery
Hormone replacement
E.g. encouraging puberty, preventing menopausal Sx and osteoporosis (if testicles removed)
How does GH deficiency present?
Short stature
Poor growth
Absent growth spurt / delayed puberty
Investigations of GH deficiency
Examination (plot growth chart)
Bloods: TFTs, IGF1, baseline pituitary hormones
GH provocation test (e.g. insulin, glucagon, arginine)
Wrist x-ray (bone maturation / age)
1st line investigation for GH deficiency
serum IGF-1
Confirmatory investigation for GH deficiency
GH provocation test
Management of GH deficiency
GH replacement therapy
Causes of congenital hypothyroidism
Thyroid gland defects (75%) – missing, ectopic or poorly developed thyroid, not inherited
Disorder of thyroid hormone metabolism (10%) – TSH unresponsive / defects in TG structure, inherited
Hypothalamic or pituitary dysfunction (5%) – tumours, ischemic damage, congenital defects
Transient hypothyroidism (10%) – maternal medication (carbimazole), maternal ABs (i.e. Hashimoto’s)
Most common cause of congenital hypothyroidism
Thyroid gland defects (75%) – missing, ectopic or poorly developed thyroid, not inherited
Most common inherited cause of congenital hypothyroidism
Disorder of thyroid hormone metabolism (10%) – TSH unresponsive / defects in TG structure, inherited
What maternal medication can cause transient hypothyroidism?
Carbimazole
Presentation for congenital hypothyroidism
Feeding difficulties, lethargy, constipation
Large fontanelles, myxoedema, nasal obstruction, low temperature, jaundice, hypotonia, pleural effusion, short stature, oedema, ± goitre ± congenital defects
Unique symptoms –> coarse features, macroglossia, umbilical hernia
Unique symptoms of congenital hypothyroidism
coarse features, macroglossia, umbilical hernia
coarse features, macroglossia, umbilical hernia
Congenital hypothyroidism
Investigations for congenital hypothyroidism
High TSH and low T4
Measure thyroid autoantibodies ± US or radionucleotide scan
Management of congenital hypothyroidism
Early detection + replacement:
Thyroxine hormone replaced with levothyroxine OD, titrate dose to TFTs + regular monitoring
Monitor growth, milestones, development
What causes T1DM?
Autoimmune destruction of beta cells of pancreas
Genetic association of T1DM
HLA-DR and HLA-DQ association
Investigations for T1DM
Random plasma glucose: ≥11.1mmol/L
2h plasma glucose: ≥11.1mmol/L
Fasting plasma glucose: ≥7.0mmol/L
HbA1c: ≥48mmol/mol / ≥ 6.5%
Presentation of T1DM
Weight loss
Polyuria & Polydypsia
Hyperglycaemia
Examples of insulin therapies of T1DM
1st line –> Multiple Daily Injection Basal-Bolus: injections of short-acting insulin before meals, with 1 or more separate daily injections of intermediate acting insulin or long-acting insulin analogue
2nd line –> Continuous SC Insulin Infusion (insulin pump): programmable pump / insulin storage device that gives regular or continuous amounts of insulin (usually rapid- acting insulin or short-acting insulin)
Types of insulin
Long acting –> Glargine, Determir
Short acting –> Lispro, Glulisine, Aspart
Examples of long acting insulin
Glargine, Determir
Examples of short acting insulin
Lispro, Glulisine, Aspart
What needs annual monitoring for T1DM?
diabetic retinopathy, nephropathy and hypertension
When does annual monitoring begin for T1DM?
12yo for diabetic retinopathy, nephropathy and hypertension
Macrovascular complications of T1DM
HTN, CHD, CVD
Microvascular complications for T1DM
retinopathy, nephropathy, neuropathy
PACES: ‘Sick day rules’ for T1DM
Explain symptoms of DKA
Check blood ketones when ill or hyperglycaemic
Recognition and treatment of hypoglycaemia
Diagnosis of DKA
“D” diabetes (BM > 11.1mmol/L)
“K” ketones (>3)
“A” acidosis (pH <7.3) or bicarbonate <15mmol/L
How is dehydration status classified in DKA?
Mild: pH <7.3 –> 5% fluid deficit
Moderate: pH <7.2 –> 7% deficit
Severe: pH <7.1 –> 10% deficit
Complications of DKA
Cerebral Oedema –> (~25% mortality)
Mx: mannitol or hypertonic saline; restrict fluid intake
Hypokalaemia (<3mmol/L)
Mx: stop insulin temporarily
Thrombosis
Mx: heparin prophylaxis (if appropriate)
Aspiration pneumonia
Inadequate resuscitation
How is cerebral oedema managed in DKA?
mannitol or hypertonic saline; restrict fluid intake
How is hypokalaemia (<3mmol/L)
managed in DKA?
stop insulin temporarily
How is thrombosis treated in DKA?
heparin prophylaxis –> (if appropriate)
Emergency management of DKA
Shocked –> 20mL/kg bolus (over 15 minutes) –> + 10mL/kg bolus if required (max 40mL/kg)
Not shocked –> 10mL/kg bolus (over 60 minutes)
Investigations (i.e. blood glucose, FBC, U&Es, blood gas, ketones) and full clinical assessment (inc. weight, GCS)
Fluid management of DKA
(1) Deficit = ((deficit* x weight x 10) – initial bolus if non-shocked) replace over 48h
(+2) Maintenance requirement (remove initial bolus if non-shocked)
First 10kg = 100mL/kg/day
Next 10kg = +50mL/kg/day
Every kg above 20kg = +20mL/kg/day
When is insulin/dextrose therapy given in DKA?
after 1-2 hours of IV fluid replacement
What are the steps of DKA management
- Emergency management
- Fluid management
- Insulin / dextrose therapy after 1-2 hours of IV fluid replacement
What is the insulin dose used in DKA?
Insulin Dose = IV 0.05-0.1 units/kg/hour
What is the Insulin / dextrose therapy after 1-2 hours of IV fluid replacement?
Insulin Dose = IV 0.05-0.1 units/kg/hour
Start dextrose when <14mmol/L
Change to SC insulin once resolving (30min before stopping IV)
Place on ECG monitor to identify hypokalaemia
NOTE: Preceded by emergency fluid management, and fluid management
Signs and Sx of cerebral oedema
Cushing’s triad of ICP (bradycardia, hypertension, irregular breathing)
Cushing’s triad of ICP
bradycardia, hypertension, irregular breathing
Classification of Obesity
Severely Obese: 99th centile
Obese: >95th centile
Overweight: 85-94th centile
RFs for obesity
low socioeconomic status, poor diet, genetics, little exercise
Investigations for Obesity
Growth chart plotting – BMI percentile chart, adjusted to age/gender
Nutritional assessment – BMI, triceps skinfold thickness
Bloods – cholesterol, triglyceride levels, endocrine assays for conditions e.g. adrenal disease
Urine – glucosuria – T2DM
Radiology – USS/CT/MRI head for specific conditions or syndromes
What is the best way to carry out a quick test for obesity?
triceps skinfold thickness
Management of obesity
Conservative:
Self-esteem and confidence building – early intervention is key
Address lifestyle (diet and exercise)
Therapeutic aims:
Reduce excess weight whilst not compromising growth
Dietary counselling
Behaviour modification (age-dependent approach)
Stepwise physical activity programme
Adherence to plan needs strong support from family
Surgical – not recommended in young people
