Endocrine Flashcards
What are the 2 layers and the sub layers of the adrenal gland?
What hormones does the adrenal gland include in the order of the layers above?
Which hormones does the medulla produce?
Cortex- glomerulosa, fasiculata, reticularis
Medulla
Cortex- aldosterone, glucocorticoids, androgens
Medulla- noradrenaline and adrenaline
What is the main role of cortisol
What three processes therefore does it increase and what happens in each
Anti insulin- increases BSL
Gluconeogenesis- amion acids to glucose
Ketogenesis- fatty acids to glucose
Glycogenolysis- glycogen to glucose
What is CAH?
What is the usual pattern of inheritance?
Why might it impact on boys fertility
What skin finding is commonly seen
Congenital adrenal hyperplasia
Enzyme defects which cause impaired hormone secretion, increased ACTH and therefore adrenal hyperplasia
Ar
Increased risk of testicular rest Tumours. Destroys normal testicular tissue
Pigmentation
Classical CAH
Which gene is involved
CYP21A
CAH
What causes the classical form?
How does it present?
What is seen on bloods?
When do you need to start aldosterone replacement?
Who does the screening test benefit the most.
Deficiency in 21 hydroxylase enzyme causes reduced progesterone to dehydrocycortisone
Reduced glucocorticoids and aldosterone. High androgens.
Picked up on newborn screening or
Vomiting and shocked baby. Hypona hyperK metabolic acidosis. Hypotension. Females with ambiguous genitalia. Undervirilised males
Raised 17OHP
When hydrocortisone less than 50mg/m2
Boys with partial enzyme activity
Classical CAH
when does the salt wasting normally occur
How do the excess androgens affect them later
10-20 days
Advanced bone age and tall but early growth plate fusion
In classical CAH what does hypertension and a suppressed renin suggest
Over treatment with fludrocortisone
CAH
What is the second most common enzyme defect
How does it present?
11 beta hydroxylase deficiency
Normal aldosterone, increased DOC causing hypertension, excess androgens
11 beta hydroxylase deficiency
What pathway is affected
What happens the electrolytes and why
How is it treated
Reduced doc to corticosterone
Raised DOC acts like high aldosterone
Spironolactone- block the aldosterone
CAH
How does 17 hydroxylase deficiency present?
How does 3B hydroxysteroid dehydrogenase present? How is it differentiated from classical CAH
Androgen deficiency. Salt wasting and hypertension. Boys appear like girls, girls don’t have puberty
Low aldosterone and cortisol. Increased DHEA reduced testosterone. Like classical CAH but both genders have ambiguous genitalia
17 OHP to progenolone ratio.
Where is the defect in STAR deficiency
What is the characteristic presentation
High up- no cholesterol to pregenolone
Males appear female
Cushings
What is the difference between disease and syndrome
What is the key presenting feature of disease
Disease=pituitary adeonma
Syndrome- all other causes
Bitemporal hemianopia
What tumours are associated with raised acth (give 4)
What sign will be common to all
Wilms Phaeochromocytoma Neuroblastoma Small cell lung Hyperpigmentation
Where is the defect in ACTH independent causes of cushings?
What is the most common acth independent cause of cushings. What is it associated with?
What other syndrome can cause it?
Adrenal itself or exogenous steroids
Malignant tumour of the adrenal cortex-Beckwith widemenn
McCune Albright
Cushings What will the electrolytes do? Why? What is the best initial screening test? What is the best next test? What should it show What are the best next tests?
High sodium low potassium. Increased cortisol blocks up and stimulates the aldosterone receptors. High glucose
24 hour urinary cortisol
Dex suppression- suppress early morning peak. If not= disease
ACTH levels. Mri brain if ACTH HIGH or ct abdo IF ACTH LOW
Adrenal insufficiency
What happens to aldosterone and acth. Why?
How does it present
In addisons what type of antibodies develop
What is addisons associated with?
How can steroids cause it?
Low aldosterone. Raised acth- negative feedback from low cortisol
Hyperpigmentation, low sodium high potassium
Pyelonephritis
Antiadrenal cytoplasmic antibodies. Autoimmune polyendocrinopathy syndrome
Suppressed normal secretion of ACTH
Adrenal insufficiency
What does the short synacthen test do?
What does it show if it is positive
What use is the long test
What is another blood test that can differentiate between primary and secondary causes
Gives exogenous ACTH
should stimulate raised cortisol- not in primary. Delayed in secondary
Long- a secondary cause will have a response. Primary won’t
Renin aldosterone ratio- high renin low aldosterone in primary causes
Normal in secondary causes
What are 2 congenital causes of adrenal insufficiency
What are the most diagnostic tests for them
CAH
X linked adrenoleukodystrophy- very long chain FAs
smith lemil opitz- serum 7 DOC
Why do UTIs in babies give a picture of adrenal insufficiency
What happens the cortisol aldosterone and renin
Aldosterone resistance!
Normal cortisol, high RAAS
What is conn syndrome and what does it cause?
Adrenal adenoma- hyper aldosterone.
What are other causes of aldosterone xs. What will be seen in bloods to dofferentiate from renal causes
Renal artery stenosis
Wilms tumours
Hypernatraemia
Hypokalaemia
High blood pressure
High aldosterone but LOW RENIN
What is the 10%rule in paheochromocytoma?
What is the most likely genetic association
10% bilateral, malignant, recurr
SDHB mutation
What does thyroid peroxidase convert
What type of hormone is thyroid hormone
Iodide to iodine
Lipid hormone
Thyroid
Why is TSH falsely high after birth
What makes up T3 and T4
Cord clamping
Thyroglobulin and iodine
Thyroid
What are the 3 most common causes of congenital primary hypothyroidism?
What is pendred syndrome
What is the inheritance of thyroid binding globule deficiency
What should be the initial Investigations be?
Thyroid a/dys genesis. Dyshormonogenesis.
Ectopic thyroid
SN deafness and hypothyroid with goitre
X linked
Bloods, ultrasound, nucleotide scan
Thyroid
What is the most common cause of acquired hypothyroidism?
What antibodies are seen?is treatment lifelong?
Do they have a goitre? Do they have eye signs?
What is seen on isotope scan
Hashimotos Anti thyroglobulin or peroxidase Yes! Yes goitre no eye signs Reduced or patchy uptake
What is sick euthyroid syndrome?
What is seen on bloods
Transient hypothyroid after surgery or illness
Low t4 normal TSH
Thyroid
What is de quervains thyroiditis
What is the typical sign
What is the pattern of disease
Thyroid disease after a viral illness
Tenderness to the thyroid
Low then normal then high
What antibodies are seen Graves’ disease normally? What type of antibodies are they?
Thyroid stimulating hormone receptor antibodies
IgG
What are the main side effects of carbimazole
Rash, agranulocytosis
Adrenal
What is the role of cortisol
What three things does it increase
What other hormones need it to work
Stress response- counter regulates insulin
Increased gluconeogenesis, glycogenolysis and ketogenesis
Glucagon and adrenaline
Thyroid
Which HLAs- hashimotos, graves
Graves-B8
Hashimotos Dr4/5
Thyroid binding globule deficiency
How is it inherited?
What is seen on bloods?
X linked
Low total t4, normal free t4
Thyroid
What are the risks of neonatal graves
Craniosynostosis, low IQ
Outline normal calcium metabolism
Which hormone inhibits this process
Vitamin D absorbed by the skin goes to the liver as 25ohvitamin D
Then to the kidney where 1 alpha hydroxylase to 1,25 vitamin d(calcitriol)
Acts on the gut to absorb more calcium
Acts on the bones to increase osteoblasts and osteoclasts and free calcium from the bone
Parathyroid increases this
Calcitonin
What is the main cause of hypoparathyroidism
What syndrome is associated with it
What is seen on bloods
Idiopathic
Di George
Low calcium high phosphate abnormally normal PTH
Pseudohypoparathyroidism
What is it
What syndrome is most likely associated
How do you differentiate from hypoPTH
Gland is normal but non responsive
Albright hereditary osteodystrophy
Won’t respond to pth stimulation, PTH will be inappropriately high
HyperPTH
What is likely to cause it?
PTH adenoma
Why does rickets affect bones?
What most likely causes it?
What is seen on bloods
What is a less likely cause?
What occurs
What gene is defective
What is seen on bloods
Formation of unmineralised growth plates
Vitamin D deficiency (sunlight or diet)
Low calcium, secondary raised PTH. LOW PO4
X linked dominant low phosphate. Can’t activate vitamin d
PHEX Gene
Phosphate low ++ but normal calcium and po4
Timing of hormone release- which hormones? Continuous Sleep related Circadian Stress Injury
Thyroid Prolactin GH Cortisol ACTH cortisol
How do you correct sodium for hyperglycaemia
Sodium + (glucose/4)
How do you calculate mid parental height for a girl? Boy?
(Mum+12.5)+ dad all divided by 2
(Dad-12.5) + mum all divided by 2
Growth hormone deficiency
What is the most likely cause of isolated deficiency?
What treatment is it most likely associated with
Idiopathic
Radiotherapy
Panhypopituitarism
What are the 2 different presentations in congenital and acquired
Congenital- gradual growth failure, poor feeding and apnoea at birth. Phenotypically atypical- short neck, small hands and feet, dental crowding
Acquired- born normal then regress, atrophy of gonads or hair, DI
What type of cns defects involve hypopituitarism
What else is seen with septo optic dysplasia?
What can cause an acquired panhypopit
Midline defects
Nystagmus and visual impairment
Meningitis, base of skull fractures and bleeds, tumours, infiltrates
What are the three roles of insulin?
What does each step do?
Glycolysis- breaking glucose into atp
Glycogenesis- glucose to glycogen
Lipogenesis- glucose to fat
What are the 4 roles of glucagon?
What does each step do?
Glycogenolysis- breaking glycogen into glucose
Gluconeogenesis- amino acids to glucose
Lipolysis- lipids to fatty acids
Ketogenesis- fatty acids into ketones
What is MODY
WHat is common to all
What is the most common subtype and how does it present? How is it treated? Prognosis?
How does type 2 present
Maturity onset diabetes
AD
Type 3- defect hepatocyte factor 1a. Adolescence. Sulphonylurea.
2- defective glucokinase enzymes. Mild diabetes. Small doses of insulin
Which HLA subtype is type 1 commonly associated with
DR 3/4
Does transient diabetes of neonate present with ketosis?
No
What is needed to diagnose diabetes
Fasting glucose
Hba1c
Random glucose
> 7
6.5 (48)
11
Puberty What happens to the HPG axis pre puberty? What happens next? What are the stages in girls? “Boys?
Dormant then increased LH in sleep- gonads enlarge Adrenarche starts because of raised DHEAs
Gnrh released pulsatile- gonads release testosterone and oestrogen
Telarche, adrenarche, gonadarche, menarche
(Breast buds, pubic hair, axillary hair, periods)
Testicular enlargement, pubic hair, phallic growth, axillary hair, growth spurt
What is the main hormone lacking in hypoglycaemic unawareness
Adrenaline
What do infants of diabetic mums have
What happens their glucagon
Transient hyper insulinism
Low glucagon
Puberty
What is the first sign in girls. What Tanner stage does this equate to?
What is the first sign in boys? What size
Breast development- Tanner 2
Testicular size- >3ml
In relation to puberty When is female peak height? When is male?
Pre menarche
Much later- at end
How and when do gonads turn male or female?
7 weeks
Start as a bipotential gonad
Y chromosome- SRY gene
Promotes the wolfinnian duct to make testosterone and makes male genitalia
Promotes anti mullerian hormone therefore female structures regress
Female=xx therefore no testosterone so wolfinnian duct regresses and Müllerian duct grows into female structures
Ambiguous genitalia If you are 46xy but appear female what is the defect? How will you appear? Do you have a uterus? What are the gonads?
Lack of androgens
Look feminine
No uterus or Fallopian tubes
Testis
Androgen insensitivity syndrome What is the karyotype? What is the inheritance? Do they have testis? If so where Do they have a uterus?
46XY
X linked
Yes- usually intra abdominal
No- bling ending vagina
What are causes of 46XY appearing female
Give 3 syndromes associated and their main features. What gene are they associated with?
Androgen insensitivity
Persisting Müllerian duct
5 alpha reductase deficiency
Gonadal dysgensis
WAGR- wilms aniridia and GU malformations
Denys drash- wilms and ambiguous genitalia
frasier- genitalia issues and renal tubule
Disease
WT1
Ambiguous genitalia If you are 46XX but appear male what is the cause? What is the most likely disease? What maternal Conditions may be associated?
Excessive androgens
CAH (classical)
Maternal tumours or drugs
Ambiguous genitalia
What is a true hermaphrodite?
What is the usual Karyotype?
What is the diagnostic label
Both ovarian and testicular tissues
70% 46Xx
Ovotesticular DSD
Precocious puberty?
What age group is it considered
What are the 2 types and how do they present differently?
What test will differentiate?
<9 boys, <8 girls
Central- presents in the normal order
Peripheral- not “
GnRH stimulation- won’t cause increased FHS or LH if peripheral cause
Precocious puberty What is the most likely central cause? What is seen on mri What treatment may cause it and why? Give three other tumours that cause it?
Hypothalamic hamartoma
Pedunculated mass on mri, can extend to third ventricle
Radiation- causes panhypopit
Astrocytomas, ependymomas, pineal
Precocious puberty
What peripheral causes might cause it
What 2 syndromes are associated
Adrenal tumours
CAH
Gonadal tumours- ovarian or testicular leidig
Fragile X
McCune Albright
McCune Albright syndrome
Gene
Mutation
Triad of issues- What endocrine issues?
GNAS
Random mutation
Fibrous dysplasia, unilateral cafe au Laits and endocrine
Hyperthyroid, cushings, precocious puberty, gigantism or acromegaly
Delayed puberty
When is it considered in boys and girls?
What is the most likely cause?
What test will diagnose “?
> 16 boys, >14 girls
Constitutional delay
Bone age delayed on X-ray
Delayed puberty
What is primary hypogonadism otherwise known as?
Give the two syndromes that cause it in boys?
Give the one in girls?
Hypergonadotrophic hypogonadism
Noonans & Klinefelters
Turners
Noonan syndrome
Associated cardiac features
Endocrine
HOCM and pulm stenosis
Delayed puberty- hypergonadotrophic hypogonadism
Klinefelter syndrome
What is the karyotype
47XXY
Turners
Karyotype
Why are they infertile
What in puberty will be early
Formation of streak ovaries- ovaries replaced by connective tissue
Andrenarche, rest late
Hypogonadotrophic hypogonadism
What 2 syndromes can cause it in boys
What commonly causes it in girls
Kallmans and Prader willi
PCOS
What autoantibodies are commonly seen in diabetes
Which are the first to appear?
GAD Ia2 insulin autoantibodies
Iaa
What are the normal insulin requirements
Pre pubertal
Pubertal
0.8 units/kg per day
1
Why might sodium be low In dka
How do you correct for low na
Pseudo hypo na
Measured na + (glucose/4)
What percentage of beta cells are lost before type 1 diabetes appears symptomatically
80-90%
What happens insulin levels in ketotic hypoglycaemia
Low
Gynaecomastia
What syndrome is it associated with?
Can it be unilateral and painful in pre pubertal causes?
Klinefelter
Yes
How do pituitary tumours present?
What hormones do you expect to be changed in craniopharyngioma?
Do they cause exaggerated growth?
Supratentorial
Deficiency in ant pot hormones and ADH- SIADH
No!
What causes acromegaly or gigantism?
What is the difference between the two?
Pituitary adenoma that secretes GNRH
Gigantism=after epiphyseal closure
What are the two basic tests used for suspected growth hormone deficiency
What is the stimulation test?
IGF1 and bone age
Cloned one arginine suppression test
Growth hormone
What does it do to blood glucose
What inhibits it?
Raises it- anti insulin
Somatostatin
Osteogenesis imprefecta
What is the rhyme to remember the subtypes
What is the inheritance
Which have blue sclera
1=won- mild to mid
2= too sad- death
3=worst to be- severe disability
4=blue no more- mildest
1&2- blue sclerae
1&4- AD, rest AR
What is an example of a biguanide?
What is the most likely side effect?
How does it work
Metformin
GI
Increases sensitivity to insulin
What is an example of a sulphonylurea?
What is the main side effect?
How does it work?
Can it cause hypo?
Glipazide
Rash
Increases insulin secretion
Yes!
Thiazolinedinedones
What is an example
How do they work
What are side effects and why might you not use in obesity
Pioglitazone
Increases sensitivity to insulin
Abdo pain headache and increases BMI
IPEX syndrome
Inheritance? Gene?
What are the three likely features
X linked- FOX3
Eczema, diabetes and imunodysregulation
Alstrom syndrome Which endocrine disease is it a rare presentation of? Inheritance Gene What are key features
T2 DM
AR
ALMS1
Short with colour blindness and hearing loss
What is the most severe form of neonatal diabetes?
How can it be treated?
DEND syndrome- dev delay, epilepsy and diabetes.
Sulphonylurea
Transient neonatal diabetes
Gene
Inheritance
ZAC
Paternal imprinting
What Chemo can cause DKA
Asparginase
What is a somogyi effect
What causes a honeymoon phase
What causes the dawn phenomenon- what is it
Rebound high BSLs when BSLs are low ON
residual c peptide
High GH- morning highs
DKA What is mild/mod/severe Why do you get fluid and electrolyte depletion How is mild managed How is mod or severe managed
Mild- ph <7.3, mod <7.2, severe <7.1
Too much glucose to the kidneys- osmotic diuresis, stimulates RAAS, low na and high K
Oral fluids and Sc insulin (0.1 units/kg four hourly)
Bolus of 0.9 if severe or shocked
Start with 0.9%NaCl- replace maint plus defecit of 7-10% over 48 hrs. Add 5% deX when BSL<17
After first hour start insulin (0.1u/kg/hr) and K infusion
What is the total daily dose of insulin- pre pubertal? Pubertal?
0.8u/kg/day
1 u/kg/day
Autoimmune polyendocrinopathy 1
Does it have a genetic association
What are the three classical associations
What else may occur
Yes- AR defects of autoimmune regulatory gene
Hypoparathyroid, primary adrenal insufficiency and chronic mucocutaneous candidiasis
Vitiligo, slope is, hepatitis diabetes gonadal dysfunction
What tumours are seen in MEN 1
Where is the defect
Ps- pancreatic adenoma, parathyroid adenoma and pituitary adenoma
Ch11
Polyendocrinopathy type 2
Is there a genetic defect
What are the two most common endocrine features?
Not usually
Hashimoto’s thyroiditis and addisons
MEN 2
Gene?
Inheritance?
Tumours in A and B
Ch 10, AD
a- calcium calcitonin and catecholamine- thyroid medulla, parathyroid adenoma and phaeo
B- big- pituitary adenoma
Belly- phaeo, GI mucosal
What insulin dose is given in mild DKA
Is this the same as the infusion used in mod- severe
0.1units/kg/dose
Yes but continuous infusion
Steroid hormone
Which is immediate release
Which have a long duration
Cholesterol
Oestrogen/progesterone, testosterone, aldosterone and cortisol
Which two hormones are tyrosine hormones
Thyroxine and adrenaline
Which hormones are peptide hormones
What type of hormone are they
Glucagon, insulin, adh, oxytocin, prolactin, ACTH and PTH
Prohormones
What is the difference between leptin and Grelin
Leptin- makes you thin- appetite suppressant
Grelin- makes you a fat gremlin- appetite stim
How does height affect DEXA scanning
What is normal, osteopenia, osteoporosis
Tall- overestimated
Short- underestimated
Normal- >-1
Osteopenia- -1–2.5
Severe less than -2.5
