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A TO REVISE - PHASE 3A > PAEDS GENETICS/ENDOCRINE TO DO > Flashcards

PAEDS GENETICS/ENDOCRINE TO DO Flashcards

1
Q

GENETICS OVERVIEW
In terms of autosomal dominant inheritance…

i) inheritance chance?
ii) general rule?
iii) pattern of inheritance?
iv) examples?

A

i) 50%
ii) AD = structural protein defects
iii) No skipped generations, inherited regardless of sex
iv) Adult PCKD, familial hypercholesterolaemia, Marfan’s, Huntington’s disease, BRCA genes

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2
Q

GENETICS OVERVIEW
In terms of autosomal recessive inheritance…

i) inheritance chance?
ii) general rule?
iii) requirements to develop disease?
iv) carrier risk in siblings?
v) examples?

A

i) 25% from 2 carrier parents
ii) AR = affects metabolic pathways
iii) Two germline mutations (2 carrier parents)
iv) 2 in 3 (66%) as you take away possibility of them having the disease
v) CF, phenylketonuria, haemochromatosis

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3
Q

GENETICS OVERVIEW
In terms of X-linked recessive inheritance…

i) who is affected?
ii) who transmits?
iii) what can occur in females?
iv) examples?

A

i) Males more than females
ii) NO male-male transmission but affected males can produce a carrier female
iii) Gonadal mosaicism may occur influenced by X inactivation (lyonisation)
iv) Haemophilia A, Duchenne’s + Becker’s, colour blindness

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4
Q

GENETICS OVERVIEW
What is genomic imprinting + uniparental disomy?
Give an example

A
  • Most genes both copies are expressed, some genes are only maternally or paternally expressed (imprinting)
  • Prader-Willi + Angelman’s syndrome both caused by either cytogenic deletions of the same region of chromosome 15q or by uniparental disomy of chromosome 15
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5
Q

GENETICS OVERVIEW
Explain the process of gonadal mosaicism

A
  • Father = mosaic sperm (some sperm with mutated gene, some sperm normal)
  • Mother = all eggs with normal gene
  • Offspring = fertilised egg > union of male DNA (sperm) with mutated gene + female DNA (egg) with normal gene
  • Every cell of embryo has one copy of mutated + one copy of normal
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6
Q

DOWN’S SYNDROME
What is the classical craniofacial appearance in Down’s syndrome?

A
  • Flat occiput (brachycephaly) + flat bridge of nose
  • Upward sloping palpebral fissures (eyes slant down + inwards)
  • Prominent epicanthic folds (skin overlying medial portion of eye + eyelid)
  • Short neck + stature
  • Small mouth, protruding tongue, small ears
  • Brushfield spots in iris (pigmented spots)
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7
Q

DOWN’S SYNDROME
Other than craniofacial anomalies, what other anomalies can be seen in Down’s syndrome?

A
  • Widely separated first + second toe (sandal gap)
  • Hypotonia
  • Single transverse palmar (simian) crease
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8
Q

DOWN’S SYNDROME
What are some complications of Down’s syndrome?

A
  • LDs + delayed motor milestones
  • Complete AVSD
  • Atlantoaxial instability = risk of neck dislocation during sports
  • Hypothyroidism, duodenal atresia, Hirschsprung’s
  • Hearing + visual impairment, strabismus
  • Increased ALL + early-onset dementia
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9
Q

PATAU’S SYNDROME
What are some clinical features of Patau’s syndrome?

A
  • Microcephalic, scalp lesions, small eyes + other eye defects
  • Cleft lip + palate
  • Polydactyly (think 13 fingers)
  • Cardiac + renal malformations
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10
Q

EDWARD’S SYNDROME
What is the clinical presentation of Edward’s syndrome?

A
  • Prominent occiput
  • Small mouth + chin (micrognathia)
  • Low set ears
  • Flexed, overlapping fingers
  • Rocker-bottom feet (flat)
  • Cardiac + renal malformations
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11
Q

FRAGILE X SYNDROME
What are some cognitive features of fragile X syndrome?

A
  • Intellectual disability
  • Delay speech + language
  • Delayed motor development (may be secondary to hypotonia)
  • Aggressive, hyperactive + poor impulse control
  • “Cocktail personality” = happy bouncy children
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12
Q

FRAGILE X SYNDROME
What are some physical features of fragile X syndrome?

A
  • Long narrow face + large ears
  • Large testicles after puberty
  • Hypermobile joints (esp. hands)
  • Hypersensitivity to stimuli
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13
Q

FRAGILE X SYNDROME
What is associated with fragile X syndrome?

A
  • Autism (up to 30%)
  • Seizures
  • ADHD
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14
Q

FRAGILE X SYNDROME
What issues can fragile X premutation carriers suffer from?

A
  • Men can get Fragile X-associated tremor ataxia syndrome (FXTAS) = intention tremor, ataxia, memory + cognitive issues as adult, white matter changes on MRI
  • Females can get FMR1-related POI (endocrinologist input)
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15
Q

TURNER’S SYNDROME
What is the clinical presentation of Turner’s syndrome?

A
  • Short stature, webbed neck, shield chest + widely spaced nipples (classic)
  • Delayed puberty, underdeveloped ovaries > primary amenorrhoea + infertility
  • Cubitus valgus
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16
Q

TURNER’S SYNDROME
What are some complications of Turner’s syndrome?

A
  • Coarctation or bicuspid aortic valve
  • Increased risk of CHD > HTN, obesity
  • DM, osteoporosis, hypothyroidism
  • Recurrent otitis media + UTIs
  • Horseshoe kidney, susceptible to x-linked recessive conditions
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17
Q

TURNER’S SYNDROME
What is the management of Turner’s syndrome?

A
  • GH therapy to prevent short stature
  • Oestrogen + progesterone replacement to establish 2ary sex characteristics, regulate menstrual cycle + prevent osteoporosis
  • Fertility treatment like IVF
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18
Q

DUCHENNE’S
What is Duchenne’s muscular dystrophy?

A
  • X-linked recessive chromosome 21 = gene deletion for dystrophin (connects muscle fibres to ECM)
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19
Q

DUCHENNE’S
What is the clinical presentation of Duchenne’s muscular dystrophy?

A
  • Proximal muscle weakness from 5y
  • Delayed milestones
  • Waddling gait
  • Gower sign +ve
  • Calf pseudohypertrophy (replaced by fat + fibrous tissue)
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20
Q

DUCHENNE’S
What is Gower’s sign?

A
  • Patient uses hands + arms to “walk” themselves upright from a squatting position due to lack of hip + thigh muscle strength
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21
Q

DUCHENNE’S
What are some complications of Duchenne’s muscular dystrophy?

A
  • Wheelchair by 13y
  • Cardiac involvement (dilated cardiomyopathy) in teenagers
  • Resp involvement
  • Survival >30y unusual
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22
Q

DUCHENNE’S
What is the medical management of Duchenne’s muscular dystrophy?

A
  • Steroids (prednisolone) appear best treatment as improves QOL, longer life expectancy + decreased progression of heart problems
  • Manage congestive HF + arrhythmias with beta blocker, ACEi.
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23
Q

DUCHENNE’S
What is another type of muscular dystrophy very similar to Duchenne’s?
How does it differ?

A
  • Becker’s = some functional dystrophin produced
  • Features similar but clinically progresses slower, average age of onset 11y with inability to walk from 20s
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24
Q

KLINEFELTER SYNDROME
What is Klinefelter syndrome?

A
  • When a male has an additional X chromosome, making 47XXY
  • Rarely even more X chromosomes like 48XXXY (more severe)
  • Chief genetic cause of hypergonadotropic hypogonadism
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25
KLINEFELTER SYNDROME What is the clinical presentation of Klinefelter syndrome?
- Often appear normal until puberty - Taller height + wider hips - Delayed puberty (lack of pubic hair, poor beard growth) - Gynaecomastia, small testicles/penis, infertility - Weaker muscles, shyness, subtle learning difficulties (esp. speech + language)
26
KLINEFELTER SYNDROME What are some complications of Klinefelter syndrome?
- Increased risk of breast cancer compared to other males - Osteoporosis - Diabetes - Anxiety + depression
27
KLINEFELTER SYNDROME What is the medical management of Klinefelter syndrome?
- Monthly testosterone injections to promote sexual characteristics - Advanced IVF techniques for infertility - Breast reduction surgery for cosmesis
28
PRADER-WILLI SYNDROME What is the clinical presentation of Prader-Willi syndrome?
- Constant, insatiable hunger > hyperphagia + obesity - Initially failure to thrive due to hypotonia - Small genitalia, hypogonadism + infertility - Narrow forehead, almond eyes, strabismus - LDs, MH issues
29
PRADER-WILLI SYNDROME What is the management of Prader-Willi syndrome?
- GH to improve muscle development + body composition | - MDT = education support, social workers, psychologists/CAMHS, physio + OT
30
ANGELMAN'S SYNDROME What is Angelman's syndrome? What is it caused by?
- Genetic imprinting disorder due to deletion of maternal chromosome 15 or paternal uniparental disomy - Loss of function of maternal UBE3A gene
31
ANGELMAN'S SYNDROME What is the clinical presentation of Angelman's syndrome?
- "Happy puppet" = unprovoked laughing, clapping, hand flapping, ADHD - Fascination with water - Epilepsy, ataxia, broad based gait - Severe LD, delayed development - Widely spaced teeth, microcephaly
32
NOONAN'S SYNDROME What is Noonan's syndrome?
- Autosomal dominant condition with defect on chromosome 12, normal karyotype
33
NOONAN'S SYNDROME What is the clinical presentation of Noonan's syndrome?
- Short stature, webbed neck, widely spaced nipples (Male Turner's) - Pectus excavatum, low set ears - Hypertelorism (wide space between eyes) - Downward sloping eyes with ptosis - Curly/woolly hair
34
NOONAN'S SYNDROME What are some complications of Noonan's syndrome?
- CHD = pulmonary valve stenosis - Cryptorchidism which can lead to infertility (fertility in women normal) - LDs, bleeding disorders (XI deficient)
35
WILLIAM'S SYNDROME What is William's syndrome?
- Random deletion of genetic material on one copy of chromosome 7 resulting in only single copy of genes from other chromosome 7
36
WILLIAM'S SYNDROME What is the clinical presentation of William's syndrome?
- Very friendly + sociable - Starburst eyes (star-pattern on iris) - Wide mouth, big smile + widely spaced teeth - Broad forehead, short nose + small chin - Mild LD, short stature
37
WILLIAM'S SYNDROME What are some complications of William's syndrome?
- Supravalvular aortic stenosis - ADHD - HTN + hypercalcaemia
38
GENETICS OVERVIEW What is non-disjunction? What is the outcome? Management? Karyotype?
- Error in meiosis where pair of chromosomes fail to separate so one gamete has 2 chromosome copies and one has none - Fertilisation of the gamete with 2 chromosomes gives rise to a trisomy - Parental chromosomes do not need to be examined, related to maternal age - 47 chromosomes
39
GENETICS OVERVIEW What is Robertsonian translocation? Karyotype?
- Extra copy of one chromosome is joined onto another chromosome - 46 chromosomes but 3 copies of one chromosomes material
40
PRADER-WILLI SYNDROME What is Prader-Willi syndrome?
- Genetic imprinting disorder due to deletion of paternal chromosome 15 or maternal uniparental disomy
41
CONGENITAL HYPOTHYROIDISM What is the clinical presentation of congenital hypothyroidism?
- Prolonged neonatal jaundice - Delayed mental + physical milestones - Puffy face, macroglossia + hypotonia - Failure to thrive + feeding problems - Coarse facies + hoarse cry
42
CONGEN HYPOTHYROIDISM What is the management of congenital hypothyroidism? What has this helped prevent? How can it be monitored?
- Lifelong PO thyroxine 30m before breakfast - Titrate dose to maintain normal growth, start at age 2–3w - Severe neuro disability (spasticity, gait issues, dysarthria) - Normal TSH levels is most important at indicating long-term well controlled thyroid disease
43
JUVENILE HYPOTHYROIDISM What is associated with an increased risk of juvenile hypothyroidism?
- Increased risk with Down or Turner syndrome
44
JUVENILE HYPOTHYROIDISM What is the clinical presentation of juvenile hypothyroidism?
(Same as adult) - F>M, cold intolerance, dry skin, thin + dry hair - Bradycardia, constipation, goitre - Delayed puberty, obesity
45
PUBERTY Explain the tanner stages for... i) breast? ii) pubic hair? iii) genitalia?
i) BI = pre-pubertal, BII = breast bud, BIII = juvenile smooth contour, BIV = areola + papilla project above breast, BV = adult ii) PHI = none, PHII = sparse, PHIII = dark, coarser, curlier, PHIV = filling out, PHV = adult iii) GI = pre-adolescent, GII = lengthens, GIII = growth in length + circumference, GIV = glans penis develops, GV = adult
46
PRECOCIOUS PUBERTY What are the 2 main types of precocious puberty?
- Gonadotropin-dependent (central/true) = premature activation of hypothalamic-pituitary-gonadal axis - Gonadotropin-independent (pseudo/false) = excess sex steroids
47
PRECOCIOUS PUBERTY What is the pathophysiology and potential causes of central precocious puberty?
Pathophysiology: LH++, FSH+ > oestrogen from ovary ++ or testosterone from testis ++ & adrenal + Causes: - Familial, - hypothyroidism, - CNS (neurofibroma, tuberous sclerosis)
48
PRECOCIOUS PUBERTY What is precocious puberty in females?
- Development of secondary sexual characteristics (thelarche) <8y
49
PRECOCIOUS PUBERTY What is the management of precocious puberty in females?
- Full Hx, ages parents went into puberty, USS of uterus + ovaries - If ok = reassure - GnRH analogues stop puberty progressing further by suppressing pulsatile GnRH secretion until she is ready
50
PRECOCIOUS PUBERTY What is precocious puberty in males?
- Development of secondary sexual characteristics <9y - Less common, more worrying
51
PRECOCIOUS PUBERTY What is the management of precocious puberty in males?
- Full Hx including ages parents went into puberty - MRI head for ?tumour - Treat underlying cause
52
PRECOCIOUS PUBERTY What causes premature pubarche (adrenarche)? How can you tell?
- Accentuation of normal maturation of androgen production by adrenal gland (adrenarche), can be late-onset CAH or adrenal tumour - Urinary steroid profile to help differentiate
53
PRECOCIOUS PUBERTY What are the risk factors with premature pubarche (adrenarche)?
- More common in Asian + Afro-Caribbean, increased risk of PCOS later in life
54
CAH What is congenital adrenal hyperplasia (CAH)?
- Autosomal recessive condition with deficiency of 21-hydroxylase enzyme - Small minority = 11-beta-hydroxylase
55
CAH What is the normal physiology of the adrenal gland?
- Glucocorticoids (cortisol) deal with stress > raise glucose, reduce inflammation, suppresses immune system - Mineralocorticoids (aldosterone) act on kidneys to control balance of salt (mineral) + Water in blood > increases Na+ reabsorption + K+ excretion
56
CAH What is the pathophysiology of CAH?
- 21-hydroxylase responsible for converting progesterone into cortisol + aldosterone - Progesterone also used to create testosterone, but not with 21-hydroxylase - Excess progesterone (as not converted to aldosterone or cortisol) gets converted into testosterone instead (high)
57
CAH What is the clinical presentation of CAH in females?
- Tall for age, facial hair, absent periods, deep voice + precocious puberty - Severe = virilised genitalia (ambiguous), labial fusion + enlarged clitoris
58
CAH What is the clinical presentation of CAH in... i) males? ii) both sexes?
i) Tall for age, large penis + muscles, small testicles, deep voice + precocious puberty ii) Skin hyperpigmentation as melanocyte stimulating hormone by-product of ACTH production (as low cortisol) > increased melanin
59
CAH what is a clue in exams that the diagnosis is CAH?
skin hyperpigmentation caused by anterior pituitary producing more ACTH. A by-product of this is melanocyte stimulating hormone which causes more melanin.
60
CAH What is a critical complication of CAH?
- Male salt-losers present in salt-losing crisis shortly after birth
61
CAH What are some investigations for CAH?
- Monitor growth, skeletal maturity, plasma androgens - High metabolic precursor levels of 17alpha-hydroxyprogesterone (used to monitor disease too)
62
CAH what is the presentation of a salt-losing crisis?
hyponatraemia hyperkalaemia metabolic acidosis
63
CAH What management is needed for females with CAH?
- Corrective surgery to external genitalia within 1st year - Definitive surgical reconstruction usually delayed until puberty
64
CAH What is the general management of CAH?
- Lifelong glucocorticoids (hydrocortisone) to suppress ACTH > normal growth - Lifelong mineralocorticoids (fludrocortisone) if there's salt loss, infants may need NaCl - Additional hydrocortisone to cover illness/surgery - Antenatal dexamethasone controversial treatment, risks>benefits currently
65
SEXUAL DIFFERENTIATION How does a male foetus produce male sexual characteristics?
- Leydig cells produce testosterone causing Wolffian duct differentiation > vas, epididymis, seminal vesicles - Later, dihydrotestosterone leads to virilised external genitalia
66
SEXUAL DIFFERENTIATION What is the process of female sexual differentiation?
- No SRY gene present so no AMH | - Mullerian duct persists which develops into ovaries + female genitalia
67
SEXUAL DIFFERENTIATION What are some causes of sexual differentiation disorders?
- CAH (#1) - Congenital hypopituitarism (Prader-Willi) - Ovotesticular disorder of sex development (true hermaphroditism) leading to both testicular + ovarian tissues as XX + XY containing cells present
68
DELAYED PUBERTY What are some causes of hypogonadotropic hypogonadism?
- Constitutional delay in growth + puberty (FHx) - Chronic diseases (IBD, CF, coeliac) - Excess stress (anorexia, intense exercise, low weight) - Hypothalamo-pituitary disorders (panhypopituitarism, Kallman's + anosmia, GH deficiency)
69
DELAYED PUBERTY What are some causes of hypergonadotropic hypogonadism?
- Chromosomal abnormalities (Turner's XO, Klinefelter's 47XXY) - Acquired gonadal damage (post-surgery, chemo/radio, torsion) - Congenital absence of the testes or ovaries
70
DELAYED PUBERTY In delayed puberty, what are some causes of... i) short stature (delayed + short)? ii) normal stature (delayed + normal)?
i) Turner's, Prader-Willi + Noonan's ii) PCOS, androgen insensitivity, Kallmann's + Klinefelter's
71
DELAYED PUBERTY What is delayed puberty in... i) females? ii) males?
i) Absence of pubertal development by 14y ii) Absence of pubertal development by 15y (more common in males)
72
DELAYED PUBERTY What are some investigations for delayed puberty?
- FBC + ferritin (anaemia), U+E (CKD), coeliac antibodies - Hormonal testing - Genetic testing/karyotyping - XR wrist to assess bone age (low in constitutional delay) - Pelvic USS to assess ovaries + other pelvic organs - MRI head if ?pituitary pathology + assess olfactory bulbs (Kallmann)
73
DELAYED PUBERTY What are the hormonal tests you would do in delayed puberty?
- Early morning serum gonadotropins (FSH/LH) - TFTs - GH provocation testing (insulin, glucagon) - IGF-1 levels - Serum prolactin
74
DELAYED PUBERTY What is the management of delayed puberty?
- Constitutional = reassure, can Tx if severe distress - F = oestradiol - Young M = PO oxandrolone (weak androgenic steroid will induce some catch-up growth but not 2ary sexual characteristics) - Older M = low dose IM testosterone for growth + sexual characteristics
75
PICA what health problems can be caused?
- iron deficiency anaemia - lead poisoning - constipation or diarrhoea - infections - intestinal obstruction - mouth or teeth injuries
76
PICA what are the causes?
- developmental problems e.g. autism - mental health problems e.g. OCD, schizophrenia - malnutrition or hunger - stress
77
PICA how is it diagnosed?
eating non-food items and: - doing so for 1 month - behaviour is not normal for child's age - has risk factors for pica
78
PICA what are the investigations?
- blood tests - anaemia, lead levels - stool tests - parasites - x-rays
79
CRYPTORCHIDISM What are the 3 types of cryptorchidism?
- Retractile (normal variant in prepubescent boys) - Palpable - Impalpable
80
CRYPTORCHIDISM What are some investigations for cryptorchidism?
- Genital exam = warm room + hands, relaxed child, try "milk" testes into scrotum - USS in bilateral impalpable testes to verify internal pelvic organs - Hormonal for bilateral impalpable testes to confirm presence of testicular tissue (record rise in serum testosterone in response to IM hCG) - Laparoscopy = Ix of choice for impalpable
81
CRYPTORCHIDISM What is the first line management of cryptorchidism?
- If unilateral monitor as most newborns descend - Wait 3m then refer to paeds urologist so they're seen by 6m - If bilateral needs urgent senior review within 24h
82
CRYPTORCHIDISM What is the management of cryptorchidism that has not resolved?
- Surgical placement of testis in scrotum (orchidopexy = before or around 1y) - May need testosterone at age 10 to start puberty if absent altogether, ?prosthesis
83
CRYPTORCHIDISM What are the reasons for performing orchidopexy around 1y?
- Fertility = optimises spermatogenesis as testis need to be below body temp - Malignancy = massive risk of seminoma in undescended testes - Cosmesis, psychological + avoid torsion
84
KALLMAN SYNDROME what is it?
genetic disorder that can be inherited via autosomal dominant, autosomal recessive and x-linked
85
KALLMAN SYNDROME what are the clinical features?
- hypogonadotropic hypogonadism - anosmia - synkinesia (mirror-image movements) - renal agenesis - visual problems - craniofacial anomalies
86
KALLMAN SYNDROME why do you get anosmia in this condition?
due to a defect in the co-migration of GnRH releasing neurons and olfactory neurons that occurs during early foetal development
87
ANDROGEN INSENSITIVITY SYNDROME what is it?
a genetic condition in which there are defects in the androgen receptor - is x-linked recessive - patients are genetically male (46XY)but develop female phenotype
88
ANDROGEN INSENSITIVITY SYNDROME what are the different types?
- complete AIS - partial AIS - true hermaphroditism
89
ANDROGEN INSENSITIVITY SYNDROME what is complete AIS?
- karyotype = 46XY - results in a completely female phenotype - external genitalia are female (clitoris, hypoplastic labia majora + blind-ending vagina) - testes may be present in abdomen - absence of pubic + axillary hair - normal breast development
90
ANDROGEN INSENSITIVITY SYNDROME what is partial AIS?
- presents with a wide range of phenotypes - can present as normal male with fertility issues - sex assignment depends on the degree of genital ambiguity
91
ANDROGEN INSENSITIVITY SYNDROME what is true hermaphroditism?
- have both ovarian tissue with follicles and testicular tissue with seminiferous tubules, either in the same organ or one on either side - external genitalia are often ambiguous
92
ANDROGEN INSENSITIVITY SYNDROME what is the inheritance pattern?
x-linked recessive
93
ANDROGEN INSENSITIVITY SYNDROME what are the results of hormone tests?
- raised LH - normal/raised FSH - normal/raised testosterone - raised oestrogen
94
ANDROGEN INSENSITIVITY SYNDROME how does it typically present?
- present in infancy with an inguinal hernia - present at puberty with primary amenorrhoea
95
ANDROGEN INSENSITIVITY SYNDROME what is the management?
- bilateral orchidectomy to avoid testicular tumours - oestrogen therapy - vaginal dilators or vaginal surgery - generally patients are raised as female - offered support and counselling
96
DOWN'S SYNDROME What are some risk factors?
- Increasing maternal age #1 (1 in 100 by 40y, increased nondisjunction), - FHx - mother has Down's (rare)
97
FRAGILE X SYNDROME What causes it?
Trinucleotide expansion repeat of CGG caused by slipped mispairing = ≤44 normal, 60–200 = premutation carriers, >200 = fragile X
98
PRECOCIOUS PUBERTY What is the pathophysiology of pseudo precocious puberty?
Low LH + FSH as gonadal or extra-gonadal source leads to increased testosterone or oestrogen
99
PRECOCIOUS PUBERTY What are the causes in females?
More common in girls, usually idiopathic or familial, occasionally late presenting CAH
100
PRECOCIOUS PUBERTY What are the causes in males?
Less common, more worrying – Pituitary adenoma (bilateral testicular enlargement suggests gonadotropin release) – CAH or adrenal tumour (small testes) – Gonadal tumour (unilateral testicular enlargement)
101
PRECOCIOUS PUBERTY What is a genetic cause of precocious puberty?
McCune Albright syndrome (café-au-lait, short stature)
102
CAH What is a major risk factor?
Consanguineous parents
103
HYPOGONADISM Name the 3 types of hypogonadism?
Primary = hypergonadotropic hypogonadism Secondary = hypogonadotropic hypogonadism Tertiary = hypogonadotropic hypogonadism
104
GONADOTROPIN DEFICIENCY What is Hypergonadotropic hypogonadism?
Primary gonadal failure - Testes or ovarian failure
105
GONADOTROPIN DEFICIENCY Briefly describe the mechanism of Hypergonadotropic hypogonadism
Gonads not working properly so less oestrogen/testosterone Increase in GnRH as less negative feedback Increase in LH and FSH Hypogonadism occurs
106
GONADOTROPIN DEFICIENCY Give 2 causes of primary hypogonadism
Hypergonadotropic hypogonadism Klinefelter’s Syndrome (47XXY) Tuner’s Syndrome (45X)
107
GONADOTROPIN DEFICIENCY What is the effect of Hypergonadotropic hypogonadism on FSH/LH and oestrogen/testosterone levels?
FSH/LH = high Oestrogen/testosterone = low
108
GONADOTROPIN DEFICIENCY What is Hypogonadotropic hypogonadism?
Secondary gonadal failure = problem with pituitary OR Tertiary gonadal failure = Problem with hypothalamus
109
GONADOTROPIN DEFICIENCY Briefly describe the mechanism of secondary hypogonadism
Less FSH and LH So less activation at gonads Girls = no response to feedback so oestrogen decreases Boys = no response to feedback so testosterone decreases
110
GONADOTROPIN DEFICIENCY Briefly describe the mechanism of tertiary hypogonadism
Less GnRH produced So less FSH and LH So less activation at gonads Girls = no response to feedback so oestrogen decreases Boys = no response to feedback so testosterone decreases
111
GONADOTROPIN DEFICIENCY Give 2 causes of Hypogonadotropic hypogonadism
1. Kallmann’s Syndrome 2. Tumours - craniopharyngiomas, germinomas
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GONADOTROPIN DEFICIENCY What is the effect of hypogonadotropic hypogonadism on FSH/LH and oestrogen/testosterone levels?
FSH/LH = low Oestrogen/testosterone = low
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GONADOTROPIN DEFICIENCY What is the treatment for hypogonadism?
Hormone replacement therapy Males = testosterone gel/injections Females = Ethinyl oestradiol or oestrogen (tablet or transdermal), progesterone added once full oestrogen dose reached
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HYPOTHALAMIC TUMOURS what are the risk factors for developing hypothalamic tumours?
neurofibromatosis undergone radiation therapy
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HYPOTHALAMIC TUMOURS what is the most common type of tumour to cause a hypothalamic tumour in children?
glioma
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HYPOTHALAMIC TUMOUR what is the clinical presentation?
- euphoric 'high' sensations - failure to thrive - headache - hyperactivity - loss of body fat and appetite - vision loss - precocious puberty
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HYPOTHALAMIC TUMOUR what are the investigations?
- full neurological examination - blood tests for CRH, GH, GnRH, TRH, dopamine and somatostatin - CT/MRI scan - visual field testing
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HYPOTHALAMIC TUMOURS what is the management?
- surgery - radiation - chemotherapy - steroids to treat brain swelling - hormone replacement/imbalance corrected
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PRECOCIOUS PUBERTY What are the causes of pseudo precocious puberty?
Causes: – Adrenal (tumours, CAH) – Granulosa cell tumour (ovary) – Leydig cell tumour (testicular)
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PRECOCIOUS PUBERTY What is the management for premature pubarche (adrenarche)?
USS of ovaries + uterus with bone age to exclude central precocious puberty
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CAH How does salt-losing crisis present?
– Vomiting, weight loss, floppiness + circulatory collapse – Hyponatraemic, hyperkalaemic, metabolic acidosis, hypoglycaemic
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CAH What is the management of salt-losing crisis?
IV 0.9% NaCl + dextrose, IV hydrocortisone
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OBESITY when does NICE recommend intervention?
tailored intervention if >91st centile assess for comorbidities if >98th centile
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OBESITY what is the most common cause?
lifestyle factors
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OBESITY what factors are associated with a higher rate of obesity?
- asian children - female - tall
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OBESITY what are the causes of obesity in children other than lifestyle factors?
- growth hormone deficiency - hypothyroidism - Down's syndrome - Cushing's syndrome - Prader-Willi syndrome
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OBESITY what are the consequences of obesity in children?
- orthopaedic problems: slipped upper femoral epiphyses, Blount's disease (a development abnormality of the tibia resulting in bowing of the legs), musculoskeletal pains - psychological consequences: poor self-esteem, bullying sleep apnoea benign intracranial hypertension - long-term consequences: increased incidence of type 2 diabetes mellitus, hypertension and ischaemic heart disease
128
UNDESCENDED TESTES what are the risks of undescended testes?
higher chance of testicular torsion, infertility and testicular cancer
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TYPE 1 DIABETES what is the most common presentation for new patients?
diabetic ketoacidosis
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TYPE 1 DIABETES what is the triad of symptoms? what other symptoms may be present?
- polyuria - polydipsia - weight loss - secondary enuresis - recurrent infections
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TYPE 1 DIABETES what are the investigations for a new diagnosis?
- FBC, U+Es, glucose - blood cultures - HbA1c - TFTs + TPO - anti-TTG - insulin antibodies, anti-GAD + islet cell antibodies
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TYPE 1 DIABETES what is the long term management?
- SC insulin - monitoring carbohydrate intake - monitoring for complications
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TYPE 1 DIABETES what are the short term complications?
- hypoglycaemia - hyperglycaemia and DKA
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TYPE 1 DIABETES what are the long term complications?
macrovascular - coronary artery disease, stroke, HTN microvascular - peripheral neuropathy, retinopathy, nephropathy
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TYPE 1 DIABETES why should insulin injection sites be rotated?
to prevent lipodystrophy
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TYPE 1 DIABETES what are the pros and cons of insulin pumps?
pros - better blood glucose control, more flexibility eating and less injections cons - difficulties learning how to use, blockages in infusion set, having it attached at all times, infection risk
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TYPE 1 DIABETES how is hypoglycaemia treated?
- rapid acting glucose + longer acting carb - if impaired consciousness use IV dextrose and IM glucagon - 10% dextrose IV
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DKA what is the clinical presentation?
Polyuria Polydipsia Nausea and vomiting Weight loss Acetone smell to their breath Dehydration and subsequent hypotension Altered consciousness Symptoms of an underlying trigger (i.e. sepsis)
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DKA what is required to diagnose DKA?
Hyperglycaemia (i.e. blood glucose > 11 mmol/l) Ketosis (i.e. blood ketones > 3 mmol/l) Acidosis (i.e. pH < 7.3)
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DKA what are the principles of DKA management in children?
- correct dehydration evenly over 48hrs - give an initial bolus followed by ongoing fluids - insulin should be delayed by 1-2hrs to reduce chance of cerebral oedema - 0.05-0.1 units/kg/hr of insulin
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DKA what are the different classifications of DKA?
Mild - pH 7.2-7.29 or bicarb <15mmol/L, dehydration = 5% moderate - pH 7.1-7.19 or bicarb <10mmol/L, dehydration = 7% severe - pH <7.1 or bicarb <5mmol/L, dehydration = 10%
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DKA what fluids are given to children not in shock?
initial bolus - 10ml/kg 0.9% NaCl over 1 hour ongoing fluids - 0.9% NaCl with 20mmol KCl in each 500ml bag 1. calculate fluid deficit based on % dehydration 2. subtract initial 10ml/kg bolus from this 3. add maintenance fluids
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DKA what are the complications?
cerebral oedema hypokalaemia aspiration pneumonia hypoglycaemia

A TO REVISE - PHASE 3A (16 decks)

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