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RACP Endo > Endo > Flashcards

Endo Flashcards

1
Q

Puberty - Signs of Onset?

A

Boys - Testes => 4mL if early (<9 yo - Then germinoma till proven otherwise, if not normal often delayed)

Girls - Breast development - thelarche(< 8 yo, if earlier then central precocious puberty but not necessarily Ca/ Might do a MRI and halt)

Pubic hair is “adrenarche” - independent of sex hormone/true puberty

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2
Q

Causes of Pathological Growth Failure

A

EPICNICS

ENDOCRINE
Pyschosocial
Iatrogenic
Chromosomal - TURNERS/Noonan’s/Down
Nutritioanl
Intrauterine - Fetal/Placental/Maternal - 85% non-syndromic IUGR babies will catch up by age 5
Chronic Disease
Skeletal - Osteochondrodysplasias
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3
Q

Baseline investigations for short stature

A

Initially - plot appropriately on growth/
Then do a bone age

- Do more if
Extreme short stature
Height below taget
Subnormal height velocity
Chronic disease
Dysmorphic (Turners/Noonans)
Precocious puberty
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4
Q

More thorough Ix for short stature?

If suspection

A 
FBE/ESR
UEC
LFT
TFT
Ca/PO4/Vit D
Coeliac
Ferritin
Karyotype girls
Cortisol
Prolactin
Bone age
Skeletal survey

//

GH STIMULATION Test
- Use glucagon - brief rise and drop in glucose

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5
Q

GH Insufficiency

Levels
Age
Prevalance

When to treat?

A

<10 mU/L
10-20 suboptimal
>20 normal

Presents at age 2-3 (From nutrition dependent to GH dependent)

1:4000

Test using stimulation test
Requires normal TFT and cortisol prior to testing

Delayed 6-12/12 of treatment will not affect future growth!
So measure for a year first

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6
Q

Failure to grow on growth hormone?

A

Technical problems:
Poor compliance/administration/storage
Wrong does

Other condition
Subclinical hypothyroid
Chronic disease/poor nutritional
Steroid
Hx of spinal irradiation

Failure:
LeRon Syndrome (GH Resistance)
Anti GH Antibodie

Once epiphyses are fused - Can’t grow any taller - Bone age >13.5 girls or >15.5 in boys

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7
Q

Tall Stature

A 
Idiopathic 
- Familial
Klinefelter
Thyrotoxic
Early Puberty (Common/Transient)
Obesity (Common/Transient)

Rare - Sotos/Marfans/Beckwith Weideman

No Ix if normal intellect/tall family

Ix - Bone age/karytoype/thyroid function/IGF1
- Futher looking if McCune Albright

No treatment - Historical tall girls had medical high estrogen to fuse epiphyses

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8
Q

Hormones of obesity

A

Leptin - “I have enough fat”
- May have leptin resistance (Melanocorticin 4 receptor)

Also negative regulation via CCK/PPY/Insulin

The only hunger Hormone is Ghrelin - fundus of stomach - pro-appetite stimulating effect

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9
Q

Pseudohypoparathyroidism

A

Truncal obesity
Short 3/4//5 metacarpals (Brachydactyly)
Round faces
Subcutatneous anomalies

20q13.2
Imprintined
Types 1A and 1C

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10
Q

Prader Willi?

Gene Locus?

Presentation?

Treatment?

A

15q11-13
Deletion
Or Uniparental disomy
Or genetic lesion in imprinting

Signalling in HPA/PG axis

Oliver shaped eyes/micrognathia
Hypotonia
Hyperphagia
Obesity
Intellectual disability/Tempers ++
Short Stature
Hypogonadotrophic hypogonadism
Small hands and feet

Treat with GH for improvement in body composition - watch for development of OSA/Adenotonsillar growth within 6/52

Early adrenarche
Treat with estrodiol/testosterone in adolescence

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11
Q

Beckwith Wiedmann

A

Dysregulation of imprinted genes at 11p15.5
(IGF (Insulin like growth factor 2) and CDKN1C Cyclin dependent kinase inhibitor)

1:14000

Neonatal macrosomic and postnatal overgrowth with organomegaly

Hyperinsulinaemic hypoglycaemia

Abdominal wall defects

Macroglossia

Midface hypoplasia
Anterior linera earlobe crease and helical ear pits
Hemihypertrophy
Increased risk of EMBRYONAL tumours (Wilms>Adrenocortical carcinoma>(Hepatoblasoma/neuroblastoma/rhabdomyosarcoma))

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12
Q

Kleinfelter Syndrome

A

XXY - Supplementary X

COMMON 1:500 Males

  • Tall stature
  • Androgen deficieny
  • Gynecomastia
  • variable cognitive/behavioural
  • Risk of germ cell tumour and osteoperosis
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13
Q

Marfan

A

FBN-1 at 15q21.1

Tall stature
Arachnodactyl (spider finger)
Scoliosis
Hyperextendable
Ectopia lentis and other ocular
Risk of aortic root prolapse
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14
Q

McCune-Albright

Gene Locus
Prevalance
Presentation

A 
GNAS gene (Subunit of G-Protein - which relays steroid hormone via adenylate cyclase and release of cAMP) 
Hyperfunction of signalling

RARE
1:100,000-1:1,000,000

- Peripheral precocious puberty (More common in girls) then switches to GnRH secreting - Central precocious puberty  
Receptor ACTH
Receptor TSH
Receptor FSH
Receptor LH

Suppressed LH/FSH

Mild hyperthyroid
Cushing Syndrome (may req. adrenalectomy)
Elevated growth hormone - Rx somatostatin
Phosphaturia - leading
Bony changes - Polyostotic fibrous dysplasia - asymmetry
Cafe au lait spots - irregular borders

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15
Q

Compare and contrast steroid vs. peptide vs. amine hormones

A

Steroids - cholesterol, cross membranes, act on nucleus for transcription (slower, longer duration), require transport in plasma (hydrophobic), sex hormones, prednisolone, cortisol, aldosterone

Peptide, synthesised as pro-molecules, stored in vesicles then free in plasma (hydrophillic), act at receptors for signal transduction coupled to internally anorched, insulin, prolactin, oxytocin, ADH, Glucagon. Fast ON/OFF

Amine - tyrosine derivatives - bound in plasma, membrane active for coupling instant (CatecholAMINES) or transported to nuclueus slower (Thyroxine T3)

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16
Q

Neonatal hypothroidism - Define central vs. other causes congenital hypothyroidism

A

Primary is thyroid issue - agenesis/hypoplasia/ectopic/dyshormonogenesis/ TSH Resistance

Vs.

Secondary (central) is pituatiry/hypothalamic issue

TSH deficiency
Panhypopit
TRH resistance
TRH deficiency
Structural
Birth aspyhxia (infarcted pituatrity)
Syndromic
Pendred (DEAFNESS/GOITRE)
Bamforth Lazarus
Ectodermal dysplasia
Kocher Deber Semilange
Hypothyroidism-dysmorphism-postaxial-Polydactyl-Intellectual disability syndrome

Transient
Maternal Rx
Maternal Antibodies (Only blocking TRABs) - D3/7/14
Maternal Iodine ++ or —

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17
Q

What sort of molecules are the thyroid hormones?

A

Iodinated tyrosines joined together (Amine Hormone)
Joining of iodine and tyrosine by TPO to make Mono-Iodo-Tyrosine (MIT) and di-iodo-tyrosine (DIT), which then joing to make T3/T4

  • T4 (Thyroxine) is storage (longer half life)
  • De-iodinated to T3 for active
  • Also de-iodinated to inactive reverse T3, more readily in sickness/pregnancy (Sick euthyroid (along with low TSH - short half life)

Deiodinases perform this - D2 is normal, D3 is for clearing plasma, upregulated D3 when sick

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18
Q

What is the Wolff-Chaikoff effect?

A

Autoregulatory effect
Inhibits “organification” in tyroid

Too much iodine - inhibition of thyroid hormone synthesis and then increased TSH

Neonates/Autoimmune individuals very sensitive to iodine exposure (And then hypothyroidism) because of failure of escape

“Escape” mechanism allows resumption of function in not infants

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19
Q

First biochemical sign of puberty?

A

Pulsatile LH - overnight - immediately pre-empts puberty

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20
Q

Treatment of precocious puberty?

A

Superagonist of GNRH - Loss of pulsatility within a few days

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21
Q

Role of binding proteins in regards to hormones?

A

Buffer of circulating
IgF1 - all bound in circulation - rapid acting, allows gradual release

Growth hormone
Sex hormones

Vs.

Insulin - no binding protein - quick on/off

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22
Q

Steroid vs. Peptide -Hormone receptor differences?

Which receptors?

A

Steroids are lipid soluble - straight through membrane then carrier to nuclear for long lasting

Vs.

Peptide - insoluble - signal

7-transmembrane - /G-Protein/cyclicAMP
(Adrenergic and others)

Jak-Stat - phosphorphylation (GH, EGF)

Insuiln/iGF -= Tyrosine kinase

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23
Q

Hormones of posterior pituitary?

Origin of posterior pituitary?

A

Vasopression/ADH
Oyxtocin

Outpouching of brain/axonals

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24
Q

Hormones of anterior pituitary

Origin?

A 
Prolactin - Amine
Growth Hormone - Peptide
TSH - Peptide
FSH/LH - Peptide
ACTH - Peptide
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25
Q

Role of FSH and LH?

A

LH - Lutenising - Acts on Leydig cells (to make testosterone) and estrogen making cells in ovary

FSH - acts to help ovaries grow, analogy in testes in seminiferous tubules that causes testes to grow

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26
Q

Prolactin regulation?

A

Only negatively inhibited - via DOPAMINE

So with hypothalamic damage - you may have elevated dopamine

Along with DDx - Prolactinoma

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27
Q

Regarding investigations for hypopituitarism

  • What would give you clinical suspicion?
  • What provocative and non-provocative investigations
A 
Poor Growth
Delayed puberty
Thyroid issues
Energy
Fluids

//

Provocative - pulsatile hormones

  • Water deprivation for ADH (Serum osmo >300 diagnostic, urine osmo >700 rules out)
  • Excercise or glucagon in order to measure GH or cortisol (and hence presume ACTH)

//
Non-provocative
- TFT (TSH alone inadequate for central)
- Prolactin - if low ?hypothalamic damage
- FSH/LH - may be appropriately low if pre-pubertal

28
Q

Regarding GH - Where is it from?

What is its target?

A

Produced from anterior pituitary
Peptide hormone
Target is liver to stimulate IGF-1

IGF-1 circulates bound to one of 6x IGF-BP (IGF Binding proteins) and is peripherally active

29
Q

Which disease has growth hormone resistance?

A

Laron syndrome

30
Q

What is the relevance of arm-span to height ratios?

A

Always 1:1 - Consider skeletal dysplasia if not

31
Q

What is the relevance of upper to lower segment ratios?

A

upper (heigh - lower): lower (pubic symphisis-floor)

  1. 7 as neonate
  2. 4 as 4-5
  3. 0 as 10-12

Neonates have larger heads and torso cf. legs.
Ratio correlates with bone age as is dependent on bone growth.

If short and higher than expected ratio (as for a younger child) then more in keeping with hormonal -

So consider hypothyroid/growth hormone deficiency

32
Q

How to calculate mid parental height?

A

Mum + 13cm for girls
Dad -13 cm for boys

Target is +/- 10cm

33
Q

In a basal-bolus insulin regime what is the proportion of basal insulin?

A

About 40% total daily on a pump

34
Q

What are the counter-regulatory hormones for hypoglycaemia

A

STEP 1 - Stop INSULIN (Lost control if S/c insulin injected)

STEP 2- Adrenaline (Adrenal medulla) Glycogenolysis/gluconeogenesis

STEP 3 - GLUCAGON (alpha cell in pancreas) glycogenolysis, gluconeogensis

STEP 4 - GROWTH HORMONE (anterior pit) - decrease peripheral glucose utilisation

STEP 5 - CORTISOL - synergistic with glucagon for gluconeogenesis, permissively gluconeogenesis in fasting states

Loss of counter-regulatory in

35
Q

Difference between insulins?

How do they work?

A

Long acting because - modification of insulin molecule

Levemir - Fatty acid moiety to bind to albumin

Lantus - modify and add a few amino acids to change pharmocokinetics

36
Q

Target HbA1C for DM?

A

In 2016- HbA1c <7.5% in all kids

In adults <7%

Adolescent years more important, probably due to interaction with IGF etc.

37
Q

How many mol of ATP for 1 mol of glucose in aerobic conditions?

A

38

38
Q

Regarding genetics of T1DM

HLA Locus for T1DM?

Risk of inheritance if
1 x 1st degree relative
2x 1st degree relative
1x identical twin

Population incidence?
Population prevalance?

A

DR3. DR4

Risk of T1m if 1st degree relative 4%
Risk of T1DM if 2 x 1st degree relatives
15%
Risk of T1DM if identical twin - 30%

Incidence of 22/100,000 in 0-15yr olds

Prevalence of ~ 1:1500
About 1 in 500 secondary school students

39
Q

Diagnosis of impaired glucose tolerance?

Diagnosis for T1DM?

A

Impaired random BG - >7.8
T1DM Random BG - >11.1

AND
Symptomatic (Polyuria/polydypsia)

Raised BSL and osmotic symptoms

40
Q

What are the autoantibodies present in T1DM?

A

ICA (Islet cell antibodies - target in cytoplasmic proteins in beta cells )

GAD-65 (Glutamic acid decarboxylase)
(80%)
IAA, (Insulin autoantibodies)

IA-2A (Protein tyrosine phosphatase)

41
Q

Monogenic Diabetes

A

Used to be MODY (Maturity onset diabest of the young)
Antibody negative at Dx (As is 15% of T1DM)
Autosomal dominant (used to require multiple generations)
12 variants
In either insulin delivery or glucose sensing

May not require insulin, instead glibeclamide in particular genetic Dx

42
Q

How to examine for goitre?

A

Stand behind
Palpate rings of trachea
If can feel all the way up - i.e. through isthmus then not uniformly enlarged thyroid - no goitre

43
Q

What role is there for measuring urinary iodine?

A

None for a given patient

Only for population level monitoring

44
Q

How frequent is congeintal hypothyroidism?

What sorts?

A

1:3000-5000

75% dysgenesis - (agenesis, ectopic)
10% dyshormonogenesis (metabolism)
5% due to hypothalamic/pituitary failure (secondary, won’t be detected on newborn screen as doesn’t have raised TSH)

45
Q

Endemic goitre?

A

Iodine deficiency, hypertrophy to more efficiently extract iodine

Occur in mountainous regions

46
Q

Dyshormonogenesis vs. dysgenesis in Thyroid dysfunction

What are the sites of pathology?

A

Dyshromonogenesis - impaired function of any step in biochemical pathway
-TPO
TG
NIS (Sodium iodide transporter)
Pendrin (Chloride iodide transporter)
TSH-receeptor
Thyrotropin-related genes (Thrytropin=TSH)

Dysgensis - no gland (Tissue Transcription Factor TTF-1, TTF2, Pax-8)

47
Q

What is Pendrin’s syndrome?

A

Dyshormonogenesis (With no uptake on isotype scanning but present on U/S) or euthyroid goitre
Congenital deafness
Mental Delay

Error in Chloride-iodide transporter on apical membrane of thyrocyte

48
Q

What genes are implicated in secondary hypothyroidism?

A

TSH related genes that function in the pituitary

Pit-1
Prop-1 (Prophet of Pit1)
HesX-1
TRH-receptor

Associated with mental retardation and midline syndromes including septo-optic dysplasia

49
Q

What sort of receptor is TSH?

A

Transmembrane

50
Q

Regarding associated malformations/broader phenotype in thyroid dysgenesis?

TTF-1/NKX2.1

TTF-2

Pax-8

A

TTF-1/NKX2.1
Respiratory distress, chronic lung disease, mental delay, choreoathetosis

TTF-2
Choanal atresia, spiky hair, cleft palate (Can trick you into thinking midline defect and secondary)

Pax-8
Renal malformation
Cryptorchidism

51
Q

When to treat neonatal transient primary hypothyroidism?

A

Tolerate 5-10

TSH >10

Commence at 10 mcg/day

Lasts a couple of months

Commences a few weeks ex-utero

More common in premature, more common still as more premature (20%)

52
Q

Regarding treatment for hyperthyroidism and pregnancy

A

Carbimazole is teratogenic

Propylthiouracil is safe in pregnancy but can cause liver failure

53
Q

Which thyroid cancer is associated with calcitonin?

A

Medullary

54
Q

Thyroglobulin is a marker of?

A

Any residual tissue post thyroidectomy?

55
Q

Thyroid cancer is associated with what previous treatment?

A

Craniospinal irradiation in ALL for example - 80% of malignant nodules have a history of radiation exposure

56
Q

MEN2 Sydnrome?

A

Multiple endocrine neoplasia,
RET ONCOGENES

In both MEN2A and MEN2B medullary thyroid carcinoma in > 90% - prophylactic thyroidectomy

MEN2A
Also Parathyroid hyperplasia 20%
Phaeochromocytoma 50%

MEN2B Phaechromocytoma

Familal medullary thyroid carcinoma FMTC - >90%

//

All RET Oncogene mutations with varied spectrum

57
Q

Incidence of coeliac disease in T1DM?

Incidence of thyroid disturbance in T1DM

A

Coeliac 4-6%, mostly asymptomatic
Screened at diagnosis and annually

Thyroid - 1 %
30% have antibodies but progression to dysfunction rare

58
Q

Causes of hypoglycaemia in neonate?

A

Transient hyperinsulin state - due to stress response +/- GDM +/- IUGR

Growth hormone deficiency - in hypopituitarism having replaced cortisol and BSL remains low, consider replacing GH also

GALT - (Galactose-1-phosphate uridylyltransferase) (FOXO3) Galactosemia

59
Q

What is glutamate dehydrogenase HI?

A

2nd most common hyperinsulinaemia
— Gain of function of GDH
Protein rich meal exacerbates hypoglycaemia
- Liver - increased ammonia production

60
Q

What is glucokinase HI?

A

Hyperinsulinaemia

- Change in setpoint of insulin

61
Q

Why is hyperinsulinaemia increasingly dangerous beyond hypoglycaemia?

A

Due to insulin switching off other forms of energy utilisation, which means no ketone generation so no safety net for the brain

62
Q

MOA of hypoglycaemia in growth hormone deficency?

A

Lack of lipolysis (and gluconeogenesis to lesser extent)

63
Q

MOA in ACTH/Cortisol deficency

A

Hypoglycaemia increased insulin sensitivity (seen in diabetes patients when they become addisonian)

64
Q

Hypopituitarism clues in neonates?

A 
Cerebral abnormaliteies
Midline abnormalities
Micropenis
Hypoglycaemia
Prolonged jaundice

Septo-optic dysplasia

65
Q

Profound post prandial hyperglycaemia and fasting hypoglycaemia?

A

GSD 0 - Glycogen synthase deficency

RACP Endo (1 decks)

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