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FRACP Exam > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

46XX disorders of sexual development

A

masculinisation external genotypic female from androgen exposure wk 8-13 gestation

1. P450 def (21 hydroxylase)

2. 3b-hydroxysteroid dehydrogenase def

3. P450 def (11 hydroxylase)

4. Mixed gonadal dysgenesis 46XY/45X

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2
Q

46XY disorders of sexual development

A

Inadequate masculinisation in male

  1. P450 def
  2. 3b hydroxysteroid dehydrogenase def
  3. Dysgenetic tests
  4. Complete/partial androgen insensitivity
  5. 5a reductase deficiency
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3
Q

5 alpha reductase deficiency

A

46XY DSD

Converts testosterone to DHT

DHT 20X potency

Clinical: ambiguous genitalia, external feminization, internal male, virilization at puberty, minimal pubic hair

Investigations: high testosterone, no DHT

Diagnosis: HCG stimulation test

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4
Q

Acquired goitre

A

Usually sporadic

Usually euthyroid

Causes: subacute thyroiditis, iodide goiter, amiodarone, lithium

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5
Q

ACTH Synacthen test

A

use: to check adrenal insufficiency

method: administer ACTH and check cortisol response

diagnostic:

  • primary (Adrenal) cause: no change in cortisol after ACTH
  • secondary (Pituitary) cause: cortisol will increase after ACTH

2 types: short and long synacthen tests

  • short: inject IM ACTH and measure cortisol at 0, 30mins and 60mins post
  • long: uncommonly used. ACTH IV over 8hrs
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6
Q

Addison’s Disease

A

pathogenesis: AI destruction adrenal cortex

primary adrenal insufficiency: absent mineralocorticoid/glucocorticoid

  • hyperpigmentation, high potassium/renin
  • low BP/glucose/sodium
  • anorexia, weakness, shock, amenorrhoea, arthralgia, poor mood, vitiligo

secondary adrenal insuff: no hyperpigmentation/hydration, hypoglycaemia more common

hyperpigmentation: due to pro-hormone cleaved into ACTH and melanocyte stimulating hormone (MSH)

investigations: low cortisol

associations: Autoimmune Polyglandular Syndromes APS I and APS II

treatment: hydrocortisone/fludrocortisone

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7
Q

Anatomy

A
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8
Q

Adrenal deficiency

  • aldosterone
A

symptoms: salt craving, vomiting, hypotension, shock, FTT, diarrhoea, weakness

electrolyes: hyponatraemia (salt wasting), hyperkalaemia, acidosis

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9
Q

Congenital adrenal hypoplasia/adrenal haemorrhage

A

all adrenal steroids LOW

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10
Q

Adrenal insufficiency

  • Cortisol
A

clinical:

  • hypoglycaemia
  • poor stress response
  • vasomotor collapse
  • hyperpigmentation
  • apneic episodes
  • muscle weakness/fatigue
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11
Q

Adrenocortical tumours

A

Most benign and secrete nothing

1. Adenomas

  • most commonly cortisol but also aldosterone
  • androgen secreting adrenal tumours secrete testosterone usually malignant

2. Carcinomas

  • rare, usually malignant
  • 50% present with Cushing’s, 25% Cushing’s and virilization
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12
Q

Aldosterone

A

class: mineralocorticoid hormone

source: secreted zona glomerulosa

action: Na/Cl reabsorption in DT/CD and excretion K/H

control: via RAS, ACTH enhances production, Plasma K/H

increase: High K/Low Na, Loss of ECF, anxiety, primary hyperaldosterone (Conn’s syndrome), secondary hyperaldosterone, RAS, constriction of IVC

decrease: Elevated Na, adrenalectomy

investigations:

  • ?HIGH: 24hr urine collection
  • ?LOW: early AM cortisol
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13
Q

Androgen insensitivity

A

46 XY

normal feminization, absense of pubic hair, primary amenorrhoea

all mullerian structures lacking and intraabdominal testes

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14
Q

Androgen insensitivity syndrome

A

incidence: 1:20,000 (most common form of male DSD)

karyotype: 46XY

mechanism: X linked mutation androgen receptor gene

clinical: female external genitalia, blind ended vagina, no uterua

  • no pubic hair, no menarche, male height

investigations: high LH/FSH/oestradiol

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15
Q

Autoimmune Polyendocrine Syndrome Type 1

A

TRIAD

1. polyendocrinopathy

  • 90% hypoPTH before 3 yrs
  • 90% AI adrenal insufficiency by 6 yrs

2. chronic candidiasis

3. ectodermal dystrophy

(30% have all 3 symptoms)

other: immune def (Ecoli sepsis), DM1, hypogonadism, pernicious anaemia, vitiligo

clinical: 1st candidiasis, 2nd hypoparathyroidism, 3rd addison’s disease

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16
Q

Insulin therapy goal BGLs

A

<5yrs: 4.5-10mmol/L

5-10yrs: 4.5-8.5mmol/L

>10yr: 4-7mmol/L

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17
Q

Biguanide

A

drug: metformin

mechanism:

  • reduced hepatic glucose production
  • increased peripheral glucose utilisation

risks: NO risk hypoglycaemia, lactic acidosis (0.03/1000)

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18
Q

Bound hormones

A

thyroid: albumin, TBG (most), thyretin

aldosterone: weak binding to albumin (1/2 life 20 mins)

testosterone/oestrogen: SHBG (44%), albumin (54%)

  • SHBG binding: strongest dihydrotestosterone>testosterone>oestrogen

cortisol: transcortin

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19
Q

CAH

11-hydroxylase deficiency

A

incidence: 1/100,000, 2nd commonest CAH (5%)

genetics: CYP11B1 gene Ch 8

pathogenesis: deficieny 11-hydroxylase enzyme prevents degradation 11-deoxycortisol/11-deoxycorticosterone

  • normal aldosterone

clinical: virilization with salt retention, hypokalaemia, HTN (65%)

diagnosis: high 11-deoxycortisol/deoxycorticosterone, low renin

treatment: glucocorticoids

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20
Q

CAH

21- hydroxylase deficiency

A

incidence: 1/15,000, 90% CAH

  • non classical 1/1000 (normal aldosterone/cortisol)

genetics: ch 6, genes CYP21P/CYP21

pathophysiology: 21-hydroxylase deficiency impairs conversion 17-hydroxyprogesterone to 11-deoxycortisol causing aldosterone/cortisol deficiency

  • salt losing 75% form also progesterone to deoxycorticosterone
  • decreased cortisol causes increased ACTH and increased androgen production

clinical:

  • onset 10-14 days
  • virilization female genitalia/male no external
  • salt wasting assoc shock/dehydration: hyponatraemia, hyperkalaemia, met acidosis, hypoglycaemia

diagnosis: ACTH stimulation test

  • high 17-OHP/ACTH/renin/testosterone, low cortisol/aldosterone

treatment: hydrocortisone/fludrocortisone

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21
Q

CAH

3 beta hydroxysteroid deficiency

A

incidence: 2% CAH

pathogenesis: impaired gonadal and steroid hormone synthesis and excess DHEA

clinical: salt wasting crisis, males hypogonadism, girls mildy virilised, precocious adrenarche

investigations: low cortisol/aldosterone/androstenedione, high DHEA

treatment: glucocorticoids/mineralocorticoids

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22
Q

DKA cerebral oedema

A

incidence: 1-5% 6-12hr post commencing tx

mortality: 20-80%

cause: osmolar shift

risk factors: higher BUN conc, low pCO2, Na not increasing with tx, treatment with bicarb

treatment: IV mannitol

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23
Q

Constitutional growth delay

A

variation of normal growth

pubertal delay 1.5-2yrs

delayed bone age

growth rate at lower limit of normal

history of family member

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24
Q

Chronic mucocutaneous candidiasis

A

definition: chronic candida nails, mucosa, skin

cause: primary defect lymphocytes to candida

causes:

Autoimmune regulator deficiency (AIRE)

  • gene: AR Ch21q22.3
  • onset: 2 months-18 years

TRIAD

  1. mucocutaneous candidiasis
  2. hypoparathyroidism (most common assoc endocrinopathy)
  3. adrenal insufficiency (2nd most common endocrinopathy)

Autosomal dominant chronic mucocutaneous candidiasis

gene: defect STAT 1
1. mucocutaenous candidiasis
2. ONLY endocrinopathy is HYPOTHYROIDISM

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25
Q

Microvasc complications DM

A

Microvascular complications

  • 98% retinopathy by 15yrs
  • 20-30% nephropathy by 15yrs

Strict glycaemic control (HbA1c<7)

  • decreased microvascular complications by 40%
  • increased hypoglycaemic events x3
  • increased weight gain
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26
Q

Congenital goitre

A

cause: sporadic

clinical:

hypothyroid: antithyroid drugs in pregnancy (iodides, amiodarone)

hyperthyroid: neonatal Grave’s disease

Pendred’s syndrome: familial goitre, SNHL

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27
Q

Congenital hypothyroidism

A

1:2,000

Dysgenesis (85%): agenesis (1/3), aplasia or ectopic (2/3)

Dyshormonogenesis (15%) (disorder of intrathyroid metabolism) with goiter (1:30,000) indicates IEM in iodine or thyroid hormone biosynthesis or maternal antithyroid drugs

  • defective thyroid iodination (10%): AR inheritance

Maternal autoantibodies (5%)

  • 1:50,000
  • passage maternal TRBAb inhibits TSH binding receptor

Clinical: normal weight/length, increased HC, hypotonia, increased fontanelles, lethargic, poor feeding, resp issues, prolong jaundice, constipation, oedema, hypothermia

Investigations: radioisoptope scanes

Treatment: oral thyroxine

Prognosis: late dx associated MR/growth retardation

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28
Q

Cortisol

A

production: zona fasciculata/reticularis of adrenal cortex

stimulation: triggered by ACTH, depression, stress, hypoglycaemia

effect:

  • antagonises insulin: increased BGL
  • increased gastric acid secretion
  • decreased T cell proliferation
  • reduced calcium absorption from gut
  • inhibits loss of Na from intestine
  • potassium excretion
  • increased BP: increased sensitivity to adrenaline/noradrenaline
  • antiinflammatory: decreased histamine secretion
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29
Q

Cushing’s Syndrome

A

definition: elevated glucocorticoids

causes:

1. ACTH dependent

  • cushing’s disease
  • pituitary hypersection ACTH by pituitary adenoma
  • bilateral adrenal hyperplasia
  • ectopic ACTH/CRH from non pit/hypo tumours
  • exogenous ACTH

2. ACTH independent

  • exogenous steroid
  • adrenocorticol adenomas/carcinomas
  • primary pigmented nordular adrenocortical disease

clinical: central obesity, failure growth, hirsutism, weakness, nuchal fat pad, acne, striae, HTN, hyperpigmentation, hyperglycaemia, osteoporosis

investigations: 24hr urinary cortisol, dexamethasone suppression test

treatment: resection pit adenoma (60-80% success), inhibitors of adrenal steroidogenesis, adrenalectomy

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30
Q

Defective bone mineralization

A

Rickets:

  • nutritional, congenital, prematurity, Vit D resistance (type I, II), neoplastic rickets, hypophosphataemic rickets, drug induced

Renal causes:

  • renal osteodystrophy, Fanconi’s syndrom

Tumour induced osteomalacia

Other: hypophosphataemia, McCune- Albright syndrome, osteogenesis imperfecta

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31
Q

Delayed puberty

A

Constitutional delay 53%

Delayed but spontaneous 19%

Hypogonadrotrophic hypogonadism 12%

Hypergonadotropic hypogonadism 13%

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32
Q

Genetics DM1

A

genes: HLA on chromosome 6

  • 90% HLA-DR3 or HLA-DR4

inheritance:

  • no family hx 0.4%
  • affected mother 2-4%
  • affected father 5-8%
  • both parents 30%
  • sibling of affected patient 5%
  • dizygotic twin 8%
  • monozygotic twin 50%

antibodies:

  • islet cell ab 80%
  • ZnT8 ab 70%
  • insulinoma-assoc protein 2 ab (IA-2) 58%
  • glutamic acid decarboxylase (GAD) ab 20%
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33
Q

Diagnosis DM1

A

One of the following:

  1. Fasting glucose> 7mmol/l
  2. Random glucose>11mmol/l
  3. 2hr glucose> 11mol/l
  4. HgbA1c>6.5%
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34
Q

Diazoxide

A

class: K channel activator

mechanism: hyperpolarisations insulin producing cells beta islets

use: hyperinsulinaemia hypoglycaemia or resistant HTN

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35
Q

Diabetic ketoacidosis (DKA) criteria

A

1. ph <7.3

2. bicarbonate <15mEq/L

3. elevated ketones

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36
Q

DM1 associated autoimmune

A

More common DM expressing HLA-DR3

Thyroid disease (no 1 association)

  • 20% anti-thyroid Ab
  • 2-5% hypothyroid

Coeliac disease (no 2)

  • 5% develop CD/gluten- sensitive enteropathy of SB
  • 7-10% antiendomysial Ab or tissue transglutaminase Ab

Adrenal disease

  • <1% autoimmune adrenalitis

Polyglandular autoimmune syndrome type 2

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37
Q

DM2

A

Cause: increasing peripheral resistance to insulin mediated glucose uptake

RFs: obesity, positive family hx, female (1.3:1.7), LBW, GDM, puberty, PCOS

Clinical: DKA or ketonuria, hyperosmolar hyperglycaemia state

Diagnosis: fasting BGL>7, random BGL>11, HbA1c>6.5

Treatment:

  • metformin (biguanide): suppresses liver glucose output and increases insulin sensitivity muscle/fat
  • thiazolidinediones: increase glucose utilization and decrease production

Comorbidities: HTN, dyslipidemia, Non alcoholic fatty liver disease

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38
Q

Endemic Goiter

A

Thyroid hypertrophy secondary to iodine deficiency

Mild deficiency: goiter during periods rapid growth

Moderate deficiency: goiter at school age

Severe deficiency: ~50% population goiters and endemic cretinism common

Endemic cretinism:

1) Neurologic type (ID, deaf-mutism, poor standing/gait, pyramidal sugns)
- due iodine/thyroid deficiency in utero affecting foetal brain development in the 1st trimester

Rx: iodine after birth causes normal thyroid function

2) Myxoedematous type (ID, deaf, neuro Sx, ALSO delayed growth and sexual development, myxedema, NO goiter).
- thyroid atrophy unclear why hypothyroidism persists post iodine administration ? selenium deficiency

Rx: IM iodinated poppy seed to women – adequate iodine for 5yrs of pregnancies, Iodination of water

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39
Q

Fetal thyroid

A

First 20 weeks: transplacental

Second 20 weeks: increased fetal T4 and hepatic thyroglobulin, dependent on maternal iodine intake (250-300mcg/day)

Birth: rapid increase TSH/T4/T3, TSH surge 30mins, T4/T3 at 24-36hrs

Postnatal: TFTs fall after first 5 days

Premature: levels lower due to immature HPA

RDS/IUGR: lower levels TFTs

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40
Q

Foetal development reproductive tract

A

5-6 weeks: gonads

  • Wolfian: SRY in males codes TDF and testes secrete testosterone/anti-mullerian hormone
  • Mullerian duct: absensce of test/AMH

9 weeks: sexual differentiation

6-10 weeks: testicular descent (complete 28 weeks)

12 weeks: genitalia distinctly formed

41
Q

Genetics DM2

A

Offspring of parents with T2DM – 40% chance

Offspring of both parents with T2DM – 60%

Monozygotic twins – 90% chance

42
Q

Growth hormone

A

pulsatile secretion binds GH-BP

effect: protein/glucose sparing and fat utilising

-induces production/secretion IGF-1 in liver

stimulated: GRF, ghrelin, exercise, fasting

inhibited: somatostatin, SRIF, leptin

IGF-1 ↓: malnutrition, CRF, CLD, hypothyroidism, obesity

43
Q

Idiopathic growth hormone deficiency

A

1:10,000

pituitary aplasia or midline defect

defects GH, GRF or GH receptor

degrees of pituitary deficiency

slow growth post birth (short + chubby), high voice, microphallus (<2cm), fasting hypoglycaemia

Test GH stimulation:

  • agents: L-Dopa, clonidine, arginine
  • measure: IGF-1/IGFBP3
44
Q

Autoimmune polyendocrine syndrome type 1

Whitaker syndrome

A

Autoimmune

Auto recessive

AIRE gene

Multiple endocrine gland dysfunction

hypothyroidism

hypogonadism and infertility

vitiligo (depigmentation of the skin)

alopecia (baldness)

malabsorption

pernicious anemia

chronic active (autoimmune) hepatitis

45
Q

Goiter

A

4-5% all children

May be euthyroid/hypothyroid/hyperthyroid

46
Q

Gonadal dysgenesis

A

mosaic mixed gonadal dysgenesis:

karyotype: mosaicism 45X/45XY

phenotype: ambiguous genitalia and 1 gonad (1 streak and 1 ova/testis)

  • 95% male phenotype, 5% ambiguous

XY mixed gonadal dysgenesis

phenotype: asymmetrical external dysgenesis, some have uterus

  • streak ovary does not produce AMH
  • eg Turner’s

XY pure gonadal dysgenesis (Swyer syndrome)

genetics: SRY gene mutation

phenotype: female phenotype, normal stature, gonads: bilateral undiff streaks not functioning

clinical: no thelarche/menarche, hypergonadotrophic primary amenorhoea

associations: high risk of cancer, WAGR syndrome, Denys Drash syndrome

47
Q

Grave’s disease

A

incidence: 1:100 11-15yrs, F>>M

risk factors: family history, HLADR3/HLAB8 gene

pathogenesis: increased thyroid function by autoantibodies (TSI)

diagnosis: high T3/T4, low TSH

clinical: irritability, muscle weakness, insomnia, tachycardia, heat intolerance, diarrhoea, weight loss, diffuse goiter, exopthalmos and lagging of upper eye lid

investigations: high T3/T4, TSH suppression

treatment: radioiodine therapy, medications (carbimazole, methimazole), and thyroid surgery

48
Q

Growth Hormone

A

secretion: peptide hormone from somatotroph cells in anterior pituitary

stimulation: GnRH, ghrelin, sleep, exercise, hypoglycaemia, fasting

inhibition: somatostatin, GH/IGF-1, hyperglycaemia, glucocorticoids

effects:

  • anabolism: stimulation osteoblasts, chrondrocytes
  • calcium retention
  • increased muscle mass
  • increased lipolysis
  • increased protein stimulus/gluconeogenesis
  • growth intestinal organs/brain/immune system
49
Q

GROWTH TERMS

Short stature

Growth failure

A

short stature: <3rd percentile

growth failure: height velocity <5th percentile for age

Investigation IF

  • height <3.5 SDs below the mean
  • height velocity<5th percentile

-

50
Q

Hashimoto thyroiditis (lymphocytic thyroiditis)

A

most common acquired hypothyroidism

autoimmune: lymphocytic inflitration

assoc goiter with pebble-like surface

1:1,000

peak adolescence F>>>M

family history 25-35%

decline in height velocity but not weight

fatigue, weight gain, pale or puffy face, feeling cold, joint and muscle pain, constipation, dry and thinning hair, heavy menstrual flow or irregular periods, depression, panic disorder, a slowed heart rate, and problems getting pregnant

elevated anti thyroid peroxidase ab

assoc AI diseases

51
Q

HbA1c aims

A

<6yrs: 7.5-8.5%

6-13yrs: <8%

>13: <7%

52
Q

Hormone response hypoglycaemia

A

plasma glucose: low normal (3.5-8.0)

insulin: low (15-120)

betaOHbutyrate (ketones): high (0.1-0.3)

lactate: normal (0.3-2.0)

cortisol: high (150-450)

53
Q

Hyperinsulinaemia Hypoglycaemia

A

genetics: genes SUR1/Kir6.2 on chromosome 11 involved in ATP dependent potassium channel of beta cells

pathogenesis:

  • glucokinase activating mutations: closure of K channels and hyperinsulinaemia
  • glutamate dehydrogenase: hyperinsulinaemia and hyperammonaemia

clinical: hypoglycaemia within days

  • non-ketotic hypoglycaemia
  • inappropriately high insulin
  • increased glucose requirements
54
Q

Persistent hyperinsulinemic hypoglycaemia of the newborn

A

1:30,000

inherited and sporadic

genetic cause: 50% with K channel defect on ch 11

  • K channels regulate insulin secretion
    cause: elevated insulin during hypoglycaemia with absent ketones
  • hyperplasia of the pancreatic beta islet cells

Symptoms: LGA, severe hypoglycaemia 1-3 hours feeding, glucose requirement 3x normal

Investigation: PET scan

Treatment: diazoxide, octreotide, ca channel blocker, surgery

55
Q

Congenital hyperthyroidism

A

transplacental transfer TSIs

masked until effect of transplacental antithyroid meds wear off

irritability, tachycardia, polycythaemia, craniosynostosis, poor feeding FTT

tx: methimazole, beta blocker

56
Q

Hypogonadotropic hypogonadism

(low gonadrotropins/gonadal steroids)

A

Isolated gonadtropin deficiency

Kallmann syndrome

Idiopathic mulitiple pituitary deficiencies

Hypothalamic pituitary tumours

57
Q

Idiopathic ketotic hypoglycaemia

A

age 18m-5 yrs

definition: hypoglycaemia post prolonged fasting with illness
cause: defective mobilisation of alanine for gluconeogenesis
symptoms: thin
investigations: low insulin, normal lactate/pyruvate, elevated GH/cortisoll/FFA/ketones
diagnosis: diagnosis of exclusion
treatment: high protein/carb meals

58
Q

Hypophosphatasia

A

1:100,000

Low activity tissue specific ALP: unable to break down ph precursor

clinical: rickets and osteomalacia
investigations: decreased ALP, increased Ca/PO4
management: diuretics, calcitonin

59
Q

Hypopituitarism

A

1:4000-1:10,000

Growth failure:

Causes

  • generic: PROP1: AR panhypopituitarism, ACTH def 30%
  • congenital: M>F, ant pit hypoplasia, absent stalk, ectopic post bright spot and associ anencephaly/holoprosencephaly
  • acquired: craniopharyngioma, germinoma, eosiophilic granuloma, trauma, infarct, HIE etc
60
Q

Hypothalamic deficiency

A

diagnosis: ↑ prolactin ↓ all other pituitary hormones

causes: craniopharyngioma, acquired hypopituitarism, congenital hypopituitarism (assoc cleft palate, holoprosencephaly, septic-optic dysplasia)

clinical: growth failure, hypothyroidism, micropenis, pubertal delay, polyuria/polydispsia

61
Q

Insulin treatment

A

30-50% long acting, 50% short

Very short acting: lispro, aspart (30-90mins)

Short acting: (2-3hrs)

Intermediate: isophane (4-10hrs)

Long acting: glargine (6-14hrs)

Require 0.5-1.0 units/kg/24 hours

62
Q

Leptin

A

Protein hormone

Regulates energy intake/expendicture/appetite/metabolism

Produced adipose tissue

Acts on hypothalamus: appetite inhibition by counterating effect of neuropeptide Y

Influence on timing puberty

Leptin resistance: homozygous receptor defect in small no. obese adults

63
Q

Leydig cell aplasia

A

No production testosterone

Female phenotype

64
Q

Medullary thyroid carcinoma

A

Parafollicular cells of thyroid

25% familial with mutation RET oncogene

1) MEN2A
- AD somatic mutation
- triad: medullary thyroid carcinoma (>90%), phaeochromocytoma (50%), parathyroid hyperplasia (20%)
2) MEN2B
- missense mutation
- triad: medullary thyroid carcinoma (>90%), phaeochromocytoma (50%), no PT, neuromas
3) Familial MTX
- medullary thyroid carcinoma >90%

Treatment: total thyroidectomy

65
Q

Methimazole

A

Mechanism: inhibits enzyme thyroperoxidase

  • prevents oxidization if iodine

Side effects: atopic rash, agranulocytosis

66
Q

Multiple endocrine neoplasia

A

MEN 1 = Werner syndrome = the P adenomas

  • pancreatic islet cell adenomas (produce insulin and gastrin)
  • pituitary gland adenoma (produce prolactin)
  • parathyroid hyperplasia or adenoma

MEN 2 – PhAT – Phaeo, adenoma (parathyroid), Thyroid ca

  • Medullary thyroid carcinoma
  • Parathyroid adenomas
  • Phaeochromocytoma
  • Also – GIT neuromas, pit tumours, adrenocortical tumours, marfanoid (Type IIB)

MEN 3 = Sipple syndrome

  • MEN 2 plus multiple mucosal neuromas and Marfanoid habitus
67
Q

Nodules

A

2% children develop solitary nodules

most benign

carcinoma 1% paed cancers

papillary and follicular 90% thyroid tumours paeds

medullary carcinoma thyroid associ MEN

68
Q

Obesity

A

1/3 all children

obese parents: 2-3x risk

Overweight or obese: 27% preschool (2-5yrs), 33% school aged (6-11yrs), 33% adolescents (12-19yrs)

Obese: 12% preschool, 18% school aged, 18% adolescents. Severe obesity: 10% preschool, 13% school aged, 13% adolescents.

Peristence in adulthood: related to age, girls>boys

Endocrine issues<1%

Obesity increases FFA increases­ glucose increases­ insulin with ­C peptide

69
Q

Osteogenesis Imperfecta

A

incidence: 1:20,000 autosomal dominant

definition: structural defect in alpha chain of type 1 collagen

clinical: blue sclera, deafness, fragile bones

Type 1: mild, most common, recurrent fractures after birth, improves after puberty

Type 2: lethal perinatal form, babies commonly LBW, multiple intrauterine fractures

Type 3: most severe non-lethal form, intrauterine fractures common, short stature, scoliosis, vertebral fractures, decreased lifespan

Type 4: moderately severe, post birth or after recurrent fractures, normal life span

70
Q

46XX or 46XY Ovotesticular DSD

A

75% XX, 10% XY, 20% mosaic

Sporadic

Clinical: amibiguous external genitalia, both ovarian and testicular tissue present, most common bilateral ovotestis

71
Q

Parathyroid hormone

A
72
Q

Persistent Mullerian Duct

A

46XY

Cause: 50% AMH gene defect, 50% AMG receptor defect

Clinical: external male phenotype, internal female

73
Q

Placental aromatase deficiency

A

46XX

Cause: aromatase deficiency prevents transfer of fetal androgen to maternal oestriol

Clinical: virilization mother and child, hypergonadotropic hypogonadism: ovaries lack oestrogen, no puberty

74
Q

Precocious puberty

A

sexual development: <9 boys, <8 girls

Central: gonadarche from premature activation HPA (GnRH dependent)

  • any CNS disorder (germinomas, gliomas, astrocytomas, ependymomas, hamartomas)

Peripheral: no HPA (GnRH independent)

  • eg McAlbright syndrome: precocious gonadarche, fibrous dysplasia, hyperpigmented lesions from G protein defect
  • adrenal adenomas/carcinomas
  • familial GnRH indep sexual precocity with premature leydig cell maturation via X-limited dominant defect with continuous production testosterone
  • hCG secreting tumours (pineal dysgerminomas/hepatoblastoma)
  • CAH
75
Q

Precocious puberty

A

CENTRAL :

  • cause: 80% idiopathic, CNS lesions, genetics, primary hypothyroidism
  • Gonadotropin dependent precocious puberty
  • early maturation of hypothalamic-pituitary axis
  • early thelarche/pubarche in girls, and testes growth/pubarche in boys.

PERIPHERAL :

  • cause: ovarian cysts/tumours, leydig cell tumours, HCG secreting tumours, adrenal tumours, pituitary tumours
  • gonadotropin independent precocious puberty
  • excess sex hormones (androgen/oestrogen) from the gonads/adrenals/exogenous/germ cell tumour

INCOMPLETE: isolated thelarche/adrenarche/pubarche in boys or girls

Management: aromatase inhibitor, SERM, flutamide, testolactone

76
Q

Premature adrenarche

A

10-25% minimal disorder adrenal steroid enzyme biosynthesis

Spectrum of normal

F>M, black>white, obese>thin

Odour first then axillary hair

Due to adrenal production 17-hydroxypregnenolone and DHEA

Slightly advanced height/bone age

77
Q

Premature thelarche

A

Usually idiopathic/sporadic

Onset 2 years

Isolated breast development

Slightly elevated FSH/LG normal oestradiol

Ovaries may have few small cysts

78
Q

Primary adrenal insufficiency

A

CAUSES

Inherited

1. inborn error of steroidogenesis

  • CAH (most common), lipoid adrenal hyperplasia,

2. Adrenal hypoplasia congenita

  • males, mutations DAX1 gene Xp21, presents neonate period

3. SF-1 deficiency

  • transcription SF-1 required for adrenal/gonadal development

4. ALD (adrenocortical deficiency)

  • associated demyelination CNS, neonatal onset rare

type I Polyendocrinopathy:

  • AR, autoimmune polyendocrinopathy/ candidiasis/ ectodermal dystrophy syndrome
  • candidiasis first, then hypoparathyroidism, then Addisons in early adolescence

acquired etiologies: AI Addisons, infections, drugs, haemorrhage adrenal gland

79
Q

Primary hypogonadism

A

syndrome of gonadal dysgenesis (XO)

klinefelter syndrome and variants (XXY)

famial XX or XY gonadal dysgenesis (XX or XY)

80
Q

Propylthiouracil

A

Mechanism: inhibits thyroperoxidase

Side effect: liver failure, agranulocytosis

81
Q

Pseudohyponatraemia

A

definition: reading of Na that is falsely low

cause: equipment that reads Na assumes that blood is 97% water and 3% solids

  • is there is an increase in solids (protein/lipids) then the reading fo Na can be inaccurately low

correction for hyperglycaemia: corrected Na= measured Na + (BGL mmol/l/4)

82
Q

Pseudohypoparathyroidism

A

definition: elevated PTH with hypocalcaemia due to PTH resistance

Type 1

  • decreased urinary cAMP response PTH
  • Ch 20 GNAS1 mutation encoding G protein surface receptor

Type 1a (most common): Albright’s hereditary osteodystrophy

  • AD maternally transmitted
  • round face, short stature, short 4th MC, obesity, DD, subcut calcification
  • assoc resistance TSH/LH/FSH/GrRH

Type 1b

  • hypocalcaemia but without physical abnormalities
  • PTH deficiency confined to kidney

investigations: low Ca, high PO4/PTH

83
Q

Primary hypoparathyroidism

A

Hypocalcaemia but NOT rickets

  1. Congenital malformations from dev abnormalities 3rd/4th brachial arches eg DiGeorge
  2. Surgical procedures
  3. Autoimmune destruction PT gland

↓calcium, ↓PTH, ↑phosphate, normal Vit D

84
Q

Pseudohypoparathyroidism

A

autosomal dominant

assoc G protein/adenylate cyclase

↓calcium, ↑phosphate, ↑PTH, normal Vit D

Tx: calcium and vit D supplementation

85
Q

Familial hypophosphatemic rickets

A

X-linked

diagnosed first few years

failure kidney to reabsorb phsophate

low serum phosphate

86
Q

Rickets

A

decreased/defective bone mineralisation

bone soft and metaphyses widen

bowing of legs on WB, thickening wrists/knees/ribs

nutritional (poor intake, poor absorption, vit D metabolic defects)

  • Vit D deficiency calcium not absorbed from intestine

Normal calcium, ↓phosphate, ↓Vit D, ↑PTH,

87
Q

Puberty in females

A

Age: mean 10.5 yrs (precocious <8yr, delayed >12yrs)

1st stage: thelarche (drive by Oe/Prog/Prol)

2nd stage: pubarche (driven by androgens)

3rd stage: peak heigh

4th stage: menarche (need 17% body fat)

88
Q

Puberty in males

A

Mean age: 11.5 (precocious<9yrs, delayed>14yrs)

1st stage: increased testicular volume (10-12 yrs 5ml, adult 15-35ml)

2nd stage: increased penile length (5cm to 9.5cm)

3rd stage: pubarche

4th stage: peak height velocity

5th stage: sperm in urine/nocturnal sperm

89
Q

Rickets

A

causes

  • vitamin D deficiency
  • calcium deficiency
  • vitamin D dependent type 1: AR defective conversion 25OHD to 1,25OH2H
  • vitamin D dependent type 2: end organ resistance vitamin D
  • X linked hypophosphatemic rickets: 1:20,000 AR/AD
  • Hereditary hypophosphatemic rickets with hypercalcuria: AR, high Ca excretion in urine
    definition: failure of mineralization of growing bones/cartilage
    clinical: asymptomatic, pain, irritability, DD, poor growth, infections, delayed closure fontanelles, craniotables, frontal bossing, costochondral junctions, wide wrists, bow/knock knees

XR: low bone density, wide growth plates

NB. Osteomalacia: impaired mineralisation post growth plate closure

Investigations: decreased Ca/PO4, increased PTH

90
Q

Sulfonylureas

A

drugs: gliclazide, glimepride, glipizide

mechanism: increases pancreatic insulin secretion

risks: weight gain, hypoglycaemia

91
Q

Congenital thyroxine-binding globulin deficiency

A

1:10,000

Low serum T4 normal free T4

Normal TSH

euthyroid

92
Q

Terms of puberty

A

Adrenarche: activation of adrenal cortex for production of androgens

Gonadarche : activation of gonads by LH and FSH

Thelarche : appearance of breast tissue

Pubarche: appearance of pubic hair

Menarche: first menstrual period

Spermarche : age at first ejaculation

93
Q

Testicular DSD

A

46XX

Cause: Yp translocation onto X, +/- SRY

Clinical: klinefelter phenotype but not as tall, infertile

94
Q

Thiazolidinediones

A

drugs: rosiglitazone, pioglitazone

mechanism: increases sensitivity of peripheral tissues to insulin

95
Q

upper:lower ratio

A

infant 1.7:1

1yr 1.4:1

10yr 1:1

decreased: hypogonadism, marfans, klinefelters
increased: hypothyroidism, dwarfism

96
Q

WAGR syndrome

A

46XY DSD

Missing copy 11p13

W- Wilm’s tumour

A- aniridia

G- genitourinary anomalies

R- mental retardation

97
Q

Pendred’s syndrome

A

gene: AR SLC26A4 gene

pathogenesis: anion transporter known as pendrin which transports iodide across apical membrane of the thyrocte into the colloid space

diagnosis: partial discharge of iodide

clinical: euthyroid, goitre worsens with deficiency

98
Q

MODY

(Mature Onset Diabetes of the Young)

A

definition: monogenic non insulin dependent DM

incidence: 2-5%

gene defects (6 major)

1. hepatocyte nuclear factor 4a (HNF4a) <10%

  • tx: sulfonylurea

2. glucokinase gene 15-30%

  • tx: diet

3. HNF1A 60%

  • tx: sulfonylurea

diagnosis:

  • gene sequencing
  • auto Ab negative
99
Q

Menstrual cycle

A

FRACP Exam (23 decks)

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