Endocrine Flashcards
Name the 2 posterior pituitary hormones
ADH, Oxytocin
What hormones are released from the anterior pituitary
TSH, FSH, LH, GH, ACTH, Prolactin
What is the role of growth hormone
Induces targets to produce insulin-like growth hormone (IGF). IGF stimulates growth and increased metabolism
Where does ACTH stimulate and what does this cause
Adrenal gland. Increased secretion of glucocorticoids to regulate metabolism and stress response
A- Where is the Pituitary located
A- Sella Turcica/ pituitary fossa - directly behind the sphenoid air cells.
Anterior Pituitary
A- From where does the anterior pituitary develop
B- How are hormones stored and released
C- What hormones are released
A- Rathkes pouch, from an invagination of buccal mucosa / endoderm
B- Communication for release is via the hypothalamus. The hypothalamus releases neurotransmitters into the hypophyseal portal vessels which trigger release of hormone from the anterior pituitary
C-TSH, FSH/LH, ACTH, Prolactin, Growth hormone
Posterior Pituitary
A- Where does the posterior pituitary develop from
B- What hormones are released
C- Where are these hormones produced
A-Neural ectoderm- Consists of neurons that are extensions of the hypothalamus. Axons make up the stalk and the neutron terminates in the posterior pituitary lobe
B- ADH, Oxytocin
C- Supra-optic and paraventricular nuclei of the hypothalamus
What is the difference between a hormone that acts as an endocrine vs a paracrine vs autocrine
Endocrine- carried by the circulation to a distant site of action
Paracrine- direct effect on nearby cells
Autocrine- affect on the tissue that secrets it
HESX1 is a homeobox gene implicated in which disorder
Septo-optic dysplasia –> hypopituitary
Growth Hormone
A) Function
B) How does it generate growth promoting affects
C) Regulation
A: affects carbohydrate and lipid metabolism and growth promotion
B- Via IGF-1. GH binds to cell surface receptors which results in transcription of IGF-1. IGF-1 increases synthesis of DNA, RNA and proteins
C: Secretion is pulsatile. Nocturnal release occurs during slow-wave sleep. GHRH stimulates, Somatostatin inhibits growth hormone synthesis and release
Gonadotrophins- FSH + LH
A- Function of FSH
B- Function of LH
C- How is FSH/LH production stimulated
D- What hormone inhibits FSH/LH production
A- FSH: stimulates ovaries to mature follicles, binds to glomerulosa cells and stimulates conversion of testosterone to oestrogen. In males, binds to Sertoli cells in males to increase seminiferous tubules and support the development of sperm
B- Males- Stimulates leydig cells to produce testosterone. Females- binds to ovarian cells to stimulate steroidogenesis
C- Hypothalamus releases GnRH in pulsatile fashion –> stimulates production and release of FSH and LH from the hypothalamus
D- Inhibin
Thyroid stimulating Hormone:
A- Function
B- What regulates it
A- binds to cell receptors on thyroid follicular cells and activates adenylyl cyclase to cause production of thyroid hormone
B- Stimulated by TRH from hypothalamus. Inhibited by Thyroid hormone and Glucocorticoids
The precursor for ACTH gives rise to what other hormone
MSH- melanocyte stimulating hormone
In what order do you loose your pituitary hormones
GH
FSH/LH
TSH
ACTH
“Get Fizzed Tom A”
Name 3 genes associated with congenital hypopituitary
1- PROP1; most common cause of congenital multiple pituitary hormone deficiencies. Presents in growth failure at approx 6 years of age- deficient in Growth Hormone, Thyroid hormone, Prolactin, FSH and LH
2- PIT-1
3- HESX1- affects production of all anterior pituitary hormones. If homozygous, septa-optic dysplasia
What is Hall-Pallister Syndrome
What are the features
Absent pituitary gland + Hypothalamic Hamartoblastoma.
PALiSTER-HaL
-Pituitary failure
-Anus imperforate
-Limb abnormalities- polydactyl
-Skull- craniofacial abnormalities
-Throat- bifid oesophagus
-Epilepsy
-Renal Abnormalities
-Hypothalamic hamartoma
-Laryngeal cleft
CRANIOPHARYNGIOMA
A- What is it
B- What area of the pituitary does it affect
C- What classical visual symptoms due you get
D- What other symptoms can you get
A- A tumour arising from Rathke’s pouch
B- Anterior pituitary
C- Bitemporal hemianopia due to optic chiasm compression
D:
-Headache, temperature dysregulation,
-Hormone deficiency:
->GH: Growth failure
-> ADH: Diabetes insidious
-> ACT: Addison crisis (due to secondary adrenal failure) - hypoglycaemia, hyperkalaemia, hyponatreamia, hypotension, fever
What affect does hypoglycaemia have on growth hormone release
Stimulates its release
Which hormone inhibits the release of Prolactin
A- Dopamine
Dopamine antagonist, pituitary tumour, disruption of the pituitary stalk will cause increased PRL release –> lactation
Name 3 factors that stimulate ACTH production
When are ACTH levels highest
Stress, Fasting, Hypoglycaemia
Upon waking - secreted in a diurnal pattern
On which part of the renal tubule does ADH act
How does ADH work
What stimulates ADH release
Collecting duct
Stimulates the translocation of aquaporions. In high concentrations, it also stimulates smooth muscle cells
Increased plasma osmolality- perceived by osmo-receptors in the hypothalamus + reduced blood volume- sensed by baroreceptors in the aortic arch and carotid sinus
Which of the following does not stimulate GH secretion
A- Insulin
B- Glucagon
C- Dopamine
D- Arginine
C- Dopamine
Insulin, Glucagon and Arginine stimulate GH releasee
How do you perform a growth hormone stimulation test
Administer Glucagon/ insulin/Arginine –> measure level post –> GH <10 on 2x occasions is a positive test for deficiency
What are 4 contra-indications to giving growth hormone
OSA, Malignancy, Fanconi anaemia, IDDM
On average, how much does a child from between the ages of
A) 1-2
B) 2-4
C) 4- puberty
D) Puberty onward
A) 30-35cm
B) 7.5cm
C) 5cm
D 5-11cm
A) How do you calculate mid-parental height for a
BOY
GIRL
B) Above what cm different is a child not inkeeping with their genetic potential
BOY: (Father height + Mother height) +13 / 2
GIRL: (Father height + Mother height) -13 / 2
B) If >8.5cm above/below your mid parental height this is not in keeping with the genetic potential
What are the feature of Hall-Pallister syndrome
PALSTER-HaL”
-Pituitary failure. polydactyl
-anal imperforate
-lung abnormalities
-Skull- craniofacial abnormalities
-Throat- bifid oesophagus and tongue
-Epilepsy
-Renal abnormalities
-Hypothalamic hartoma
-Laryngeal cleft
What test is used to check for Growth hormone deficiency
GH stimulation test
Give insulin/glucagon/clonidine/arginine and test growth hormone for 2 hours to see if rises
If it doesn’t central GH deficiency
what are the side effects of growth hormone
T2DM
SUFE
Gynaecomastia
OSA
Benign intra-cranial HTN
Not used in cancers
SHOX gene is implicated in what
In what syndromes would you find more and less of it
SHOX= important for growth and expressed in chondrocytes.
Carries on the X and Y chromosome
Turner - less of it –> short
Klinefelters XXY –> too much of it –> tall
What is the abnormalities in Russel Silver syndrome
What are the symptoms
IGF-2 inappropriate methylation/ uniparental disomy etc
Sx; triangular face with large head, FTT, hemiatrophy, growth failure
What is the key difference between familiar short stature vs constitutional delay
Familial- normal growth velocity, bone age <1 separate year from chronological age, normal puberty onset, Final height short
Constitutional- bone age >1 year delayed from chronological age. Puberty delayed. Final height normal
NSD1 gene is implicated in what disorder
Soto syndrome
Soto syndrome
-what gene
-what sx
NSD1 gene
Sx: tall childhood growth velocity, frontal bossing, high arched palate, hypertelerosim, behavioural issues
What is the investigation for Diabetes Insipidus
Water deprivation test
-Keep testing until serum osmalaity >295
-failure to concentrate urine
-then give DDAVP
-If responds = central; if no response= nephrogenic
NDI gene on the X-chromosome is seen in what condition
Neonatal diabetes insipidus
Mutation of the V2 receptor –> congenital nephrogenic DI
What are nephrogenic causes of DI
Mutation at V2 receptor
Aquaporion mutation
Concentrating syndrome
-Bartter syndrome
-Gitteman Syndrome
What is inappropriately excreted in cerebral salt wasting
What effect does it have on
-blood pressure
-serum Na
-urine Na
-urine output
What is the treatment
ANP- atrial natureitic peptide
-Blood pressure: lower
-Blocks Aldosterone secretion –> lower sodium reabsorption –> reduced serum sodium
-urine sodium = very high
-urine output = very high
TX: IV Fluids with NaCl
What are causes of SIADH
What affect does it have on
-serum osmolality
-urine osmolality
-serum Na
-urine Na
-Blood pressure
What is the treatment
Infection- meningitis
Trauma
2nd part of recovery from neurosurgery (death of Anterior pituitary cells
Overdose of DDAVP
Serum osm: low
Urine osm: high
Serum Na: low
Urine sodium: relatively high
Blood pressure: normal
Fluid restrict
Salt replace
Urate crystals
Tolvaptin
What is the treatment of diabetes insipidus
Access to free water
Salt and protein restriction
Thiazide diuretic- trick proximal tubule to absorb more water
DDAVP
What features do you get in pseudohypoaldosteronism
What causes it
Signs of mineralocorticoid deficiency e.g. hyperkalaemia, hyponatraemia, hypotension
BUT high renin and high aldosterone
In true hypoaldosteronism get high renin but low aldosterone
Cause: loss of function mutation on sodium channel
What are the features of Liddles syndrome and why
What is the treatment
Liddles- gain of function mutation of epithelial sodium channel
Results in pseudohyperaldosteronism
-hypokalaemia, HTN
-metabolic alkalosis
-renin and aldosterone levels low
Treatment = aliloride which block the channel
what test would you order for paeochromocytoma
plasma noremetanephrine test
What do you get in
MEN III
MEN II
MEN I
MEN III:
-Medullary thyroid hyperplasia
-Medullary adrenal hyperplasia - phaeochromocytoma
-Mucosal neuroma
MEN II:
-Medullary thyroid neoplasm
-Medullary adrenal gland - phaeochromcytoma
-Parathyroid hyperplasia
MEN I
-parathyroid hyperplasia
-pituitary tumour
-pancrease carcinoma
What features do you get in 17OH deficiency
Cannot form cortisol and androgens. Only get androgen deficiency because deoxycortisone acts like cortisol.
Males= under-virilization
Female= lack of progress via puberty
Testing:
-reduced DHEA and androgen
-reduced cortisol
-increased ACTH
TX
-Hydrocortisone to reduce ACTH so not causing mineralocorticoid excess
-Testosteron/Oestrogen supplements
What occurs in a 3BHDH deficiency
What do you see on lab tests
What do you see externally
Cannot synthesis any elements in the cortex except DHEA
-deficiency in aldosterone, cortisol and androgens
Get
-low blood sugar, low blood pressure
-hyponatraemia, hyperkalaemia, metabolic acidosis
-increased renin and ACTH
-reduced Aldosterone and cholesterol
-increased DHEA
Males= undervirilisation + salt wasting
Females= may get mild virilization due to increased DHEA
What occurs in 21-OH deficiency
What do you see on labs
What do you see externally
Cannot form aldosterone and cortisol
Results in adrenal insufficiency of these areas and increased androgen production
Labs:
-increased DHEA, Androgen
-increased ACTH, reduced cortisol, no synacthen response
-increased Renin, reduced aldosterone, hyponatraemia, hyperkalaemia, metabolic acidosis, low blood pressure
External:
Female- virilzation of external genitalia
Male- no affect- present in crisis due to salt wasting and lack of cortisol response in stress
What occurs in a 11-B OH deficiency
What occurs in lab
What do you see symptomatically
Cannot form Cortisol only. Nil issues with mineralocorticoids or androgens
Labs:
-increased ACTH, reduced cortisol, nil response to synacthen
-Slightly increased androgens
-Normal renin and aldosterone as renin regulates this pathway
-INCREASED DEHYDROXYCORTISOL
What are the zones of the adrenal cortex and what do they produce
Zona Granulosa- Mineralocorticoids
Zona Fasciculata- Glucocorticoids
Zona Reticularis - Androgens
What age is the adrenal gland made
when does it begin steroid production
8 weeks
9-12 weeks
What are the features of McCunes Albright syndrome
Coast of Maine birth spot
Fibrous dysplasia
Endocrine hyperfunction e.g. oestrogen producting cysts, hyperfunction of adrenal gland
What test helps differentiate primary vs secondary Cushings syndrome
Dexamethasone suppression test
-Give 11pm dose of dexamethasone
-should suppress ACTH secretion
-check cortisol mane
-if reduced cortisol, secondary causes (pituitary adenoma secreting ACTH)
-if nil change to cortisol, ACTH independent lesion e.g. adrenal adenoma
When is the best time in cushings to check a cortisol level
midnight- reverse of normal cortisol peak elevation
What is conns syndrome
Aldosterone secreting adrenal tumour
How do you investigation primary vs secondary adrenal insufficiency
Short Synacthen test
What is an adrenal crisis
Decompensation due to hypo functioning adrenal system in context of a stressor
-Cortisol: low BSL, hypotension
-Aldosterone: hyperkalaemia, hyponatraemia, hypotension, metabolic acidosis
What are 4 causes of hyperaldosteronism
-Conns syndrome
-Renal artery stenosis
-Renin secreting tumour
-Reduced ECF volume e.g. nephrotic syndrome
DAX1 mutation is seen in what
congenital adrenal hypoplasia
What is a STAR mutation and what is the result
Affects cholesterol uptake in to the adrenal gland
Nil uptake -> nil dyshormogenesis
In males, results in undervirilization
In both causes salt wasting and cortisol deficiency
What is given to stop idiopathic central precocious puberty
GnRH - Lucrin - stops pulsatile GnRH so FSH and LH are secreted
How do you differentiate peripheral vs central precocious puberty
GnRH stimulation test
-in central you get a LH increase
-in peripheral you do not
what are the features of Kallman syndrome
How is it inherited
Why does it occur
Anosmia
Microphalus
Cryptoorchidism - hypogonadotrophic hypogonadism
Midline facial abnormalities
X-linked
Neuronal migration issue for olfactory and GnRH secreting neurons
what hormones would you check to look for testicular cell function
AMH and Inhibin B
what test do you perform to see if the testicles are capable of secreting testosterone
HCG stimulation test
How does GnRH FSH and LH differentiate thelarche vs central puberty
FSH dominant response in thelarch
LH dominant response in central puberty
what is the treatment for McCune Albright
oestrogen blocker- tamoxifen
aromatase inhibitor - anastrozole, letrozole
what do these tests show about testicular function
-hCG stimulation test
-Inhibin B
-AMH
hCG: reveal functional leydig cells. hCG stimulates LH receptors on Leydig cells to stimulate testosterone production
Inhibin B: made be Sertoli cells (and germ cells in puberty). Assesses presence of functional sertoli cells
Inhibits FSH secretion
AMH: secreted until puberty. marker of Sertoli cell function
What is IPEX
What causes it
Immune dysfunction polyendocrinopathy X-linked
Mutation of a gene that controls T-regulator cells
What are the symptoms of Autoimmune Poly-endocrinopathy type 1
Hypoparathyroidisim
Addisons disease
Mucocutaneous candititis
What are the 3 auto-antibodies in diabetes
What order do they appear
anti glutamic acid decarboxylase (anti-GAD)
Anti insulin associated antigen (anti-IAAS)
Anti-islet antiget (Anti-IA2)
IAAS is the first to occur
Followed by anti-GAD
When giving subcut insulin to a mild DKA new diagnosis
what units/kg do you give for a pre-pubescent vs pubescent child
pre-pubescent: 0.5-1.2unit/kg/day
pubescent: 0.7-1.5units/kg/day
What type of insulin is Humulin R and Actrapid
How long is their duration
Short active
Onset within 30min
Peak: 3 hours
Duration- 8 hours
what type of insulin is protophane? how long is its duration
when is its peak
Intermediate acting
16 hours
peak 4-10 hours
what type of insulin is insulin-glargine
what is its duration
Lantus- long acting
24 hour duration
No peak
What is another name for Humalog insulin lispro
nova rapid
What type of insulin is Humulin NPH
Duration of action?
Peak?
Intermediate
Also known as protaphane
16 hours
Peak= 4-10 hours
what is the recommended k-calorie intake for a diabetic
what % is carbs/protein/fat
1000kCal + 100kCal per year of age
50% carbs
30% fat
20% protein
what is the somogyi phenomenon
hyperglycaemia ==> early night hypoglycaemia due to overshoot of anti insulin hormones in a child with well controlled diabetes
management = reduce night time insulin
what is the mechanism of action of metformin
how does it work
what are the side effects
increased AMPK protein kinases
Stops liver Gluconeogenesis
Stops GI absorption of glucose
Increases peripheral sensitivity to insulin
S/E
=GI upset
=Lactic acidosis as lactic acid cannot enter Gluconeogenesis in the liver
How do SLGT2 inhibitors work
What are the side effects
Block sodium/glucose reabsorption in the proximal tubule
Result = increased glucose loss in the urine so better serum glucose.Also causes osmotic diuresis = better blood pressure = better renal protection
S/E
-Euglycaemia DKA
-Vaginal candititis
-UTI
-Infection in genital region –> necrotising fascities
-Hypovolaemia especially if on ACE inhibitor or diuretic
What is the mechanism of action of GLP-1 mediation
How does that work in the body
What is at the end of their drug name
What side effects
Glucagon like peptide agonist
Bind to glucagon receptors
-In pancreas, increase insulin secretion, reduce glucagon secretion
-Liver: reduced gluconeogeneis
-Peripheries: increased sensitivity to glucose
-reduced gastric emptying and reduce appetite to trigger weight loss
“Glutide”
S/E: nausea, vomitting, diarrhoea
how do GPP-4 medications work in diabetes
Bind to enzymes to stop the break down of GLP - glucagon like peptide and and GIP-gastric inhibitory peptide (stimulates insulin secretion)
What defects do you see in
MODY1
MODY2
MODY3
MODY4
MODY5
What treatment is needed for
MODY2 and MODY3
What is the difference in their proinsulin: insulin ration
What is the most common form of MODY
MODY1: HFN-4a
MODY2: Glucokinase
MODY3: HFN-1a
MODY4: IPF1
MODY5- HNF-1b
Mody 2= no treatment. Results in slightly higher baseline for insulin release but released once BSL>7. No deterioration. No microvascular complications
Mody 3: sulfonurea and then eventually insulin. Results from impaired transcription of potassium channel and insulin
Mody2= normal pro-insulin : insulin
Mody 3= increased pro-insulin: insulin
MODY3
Where does the thyroid gland form from
What gestation does it migrate to the neck
Floor of the pharynx- a midline out pouch from the buccal cavity
Week 7
Why is a foetus at risk of a hypothyroid mother
1/3 of maternal T4 crosses the placenta. Thyroid hormone is essential for brain development
Fetus doesn’t start production until approx 10-12 weeks with risk in levels from mid-gestation
Therefore reliant on maternal thyroid hormone
why is it important to test thyroid hormone on a Guthrie on day 3 onwards
Cord clamping and cold stress cause a surge in TSH. This falls after 24 hours
If tested early, can cause false positive if tested before TSH surge has stopped
Describe thyroid hormone synthesis
TRH binds to a G-protein coupled receptor on the thyroid follicle.
Stimulates increased intra-cellular cAMP
Leads to increased transcription of thyroglobulin
Thyroglobuin then passes into the colloid of the cell
Na/I cotransporter uptake iodide from the cell
Iodide is pumped into the colloid via a Cl-/Iodine transporter
The enzyme PERIOXIDASE converts iodide to iodine
Iodine binds to tyrosin rings on the thyroglobulin molecule
-1 iodine molecule = monoiodinetyrosin (MIT)
-2 iodine = diiodinetyrosin (DIT)
MIT+DIT = T3
DIT + DIT= T4
-Thyroglobin and MIT/DIT structure then is taken back into the follicle cell by pinocytosis
-Lysosomes break the thyroglobin off to release molecules of T3 and T4
-Iodine is recycled also to allow the process to be repeated
what is the role of thyroid peroxidase in thyroid hormone production
converts iodide –> iodine
allows organification by the binding of iodine to thyroglobin tyrosine molecules
in. radioactive thyroid scan what does a hot scan vs cold scan show
-hot scan: increased uptake due to increased thyroid hormone production = thyroiditis, graves
-cold scan= area of reduced uptake. carcinoma until proven otherwise
what is the most common cause of thyroid dysgenesis
ectopic thyroid gland
what causes a goitre in primary hypothyroidism due to dyshormonogenesis
increased TSH production
what is the most common enzyme implicated in dyshormonogensis
what is the result
thyroid peroxidase
unable to iodinate thyroglobulin
what is Fanconi-bickle syndrome
GLUT 2 mutation so glucose is not released from the liver or nephrons
Results in hepatomegaly and eventually proximal tubular nephropathy
Get short stature
What is DEND syndrome
KCNJ11 mutation causing epilepsy, neonatal hypoglycaemia and developmental delay
KCNJ11 mutation is implicated in what disease
DEND syndrome- epilepsy/neonatal hypoglycaemia/developmental delay
what differentiates thyroid hormone resistance from Graves disease
Graves you get suppression of the TSH
In thyroid hormone resistance the pituitary is also resistance to thyroid hormone so doesn’t’ recognise it ==> elevated TSH without evidence of hyperthyroidism
what occurs in fetal congenital hypothyroidism
maternal IgG antibodies bind to TSH receptors and block them
Result - lack of T3 and TSH production, increased TSH
in fetal congenital hypothyroidism how long does maternal IgG last
When does it resolve by
21 days
2-3 months
what does neonatal screening for congenital hypothyroidism screen
what does it miss
TSH
Will miss central causes of hypothyroidism as won’t get increased TSH e.g. from pituitary or hypothalamic dysfunction
If there is no uptake of radionucleiotide scan but a normal gland on ultrasound what is the next test
DDX: TSH receptor blocking antibodies OR TSH resistance
TSH receptor antibody levels
When starting levothyroxine how often do you monitor level
Weekly for first 4 weeks
Then monthly until 12 months
Then 2 monthly until 24 months
Then 3 monthly
Name 5 causes of hypothyroidism
1) Central- pituitary/hypothalamic dysfunction
2) Congenital
-dysgenesis of the gland
-disorder of hormonogensis
-Thyroid hormone resistance
3) Autoimmunie
- Hashimotos
4) Alloimmune
-maternal IgG antibodies blocking TSH receptors
5) External
-iodine deficiency
-phenytonin, phenobarbital, valporate
-amiodarone
what drugs cause hypothyroidism
-phenytonin, phenobarbital, valporate
-lithium
-amiodarone
Name 5 causes of hyperthyroidism
1) Autoimmune
-Graves disease
2) Congenital
-Thyrotropin receptor activating mutation
3) Drugs:
-iodine, contrast
-amiodarone
4) Cancer: toxic adenoma
5) External
-McCune Albright syndrome
In what % of children with Down and Turner develop anti-thyroid antibodies
30-40%
what is the half life of levothyroxine
how long until it reaches steady state
6 days
3.5 weeks
how does carbimazole work
blocked the thyroid peroxidase enzyme
what antibodies cause hashimotos
anti-thyroglobin
anti-perioxidase (anti-TPO)
what type of hypersensitivity reaction is hashimotors
Type 4 - activated CD8 cells which have been recruited by B-cells responding to a antigen they are hypersensitive to
Describe autoimmune polyendocrinopathy type 1 and type 2
Type 1= HAM
hypopituitary, Addisons, mucocanditis
Type 2= HAD
-Hashimotos, adrenal insufficiency, diabetes
what would you see on radio iodide scan in Hashimotos
patchy irregular uptake
Name 5 causes of hyperthyroidism
-central hypopituitary tumour
-autoimmune: graves
-alloimmune: maternal graves disease
-cancer: solitary adenoma, toxic multi-nodular goitre
-inflammation: thyroiditis
-iatrogen: excess intake of levothyroxine, contract
-syndrome: McCune albright
hyperthyroid + diffuse goitre=
graves disease
what is the physiology of graves disease
B-cell produced anti-bodies mimic the TSH molecule and can bind to the TSH receptor, up regulating thyroid production
T3 and T4 increase
Negative feedback on the HPA axis so TSH is suppressed
Why do you get eye and skin and muscle signs in hyperthyroidism
antibodies are not unique to the TSH receptor
Also bind to the eyes and legs
Result
-proptosis + opthalmoplegia
-skin: myxoedema
-muscle: wasting
as body attacks itself in this manner with lymphocyte infiltration
What antibodies do you see in Graves disease
Thyrotropin receptor stimulating antibodies
what test is used to assess for the presence of ectopic thyroid tissue
scintigraphy
what is the best measure of thyroid function when treating congenital primary hypothyroidism to ensure normal development
TSH- most sensitive marker
What are some foods/minerals that interfere with levothyroxine absorption
soy
iron
calcium
antacids
when is secretion of TSH highest
At night
A child has high TSH and low T3 and T4
You check autoantibodies by these are negative
-what antibodies do you check
-what is your differential diagnosis
Anti-TPO
Anti-Thyroglobulin
Iodine deficiency
thyroid injury
CH
Liver haemangiomas
A child has symptoms of hyperthyroidism with a low TSH and high T3 and T4
-what antibodies do you order
-if these are negative what is your differential
TSI and TPO
If TSI and anti TPO increased: Graves
If TSI low and increased TPO/anti-TG= autoimmune thyroiditis
If both negative- nodule or drug induced
What is the reason PTU (Propylthiouracil) is not used in children except for in adolescents during pregnancy
What other side effects does it have
Hepatotoxicity
Transient Granulocytopenia
What is Carbimazoles MoA
How long does it take to work
What is used in conjunction
Blocks thyrohomonogensis by blocking thyroid perioxidase
Onset-6-8 weeks
B-blockers used to reduce tachycardia and act as peripheral blockers by reducing the conversion of T4 –> T3
ADR
-agraulocytosis
-liver failure
-urticaria, myalgia
After thyroid removal, development of a hoarse voice is due to damage of what nerve
Recurrent laryngeal nerve
what percentage of children with graves achieve remission
25%
what monoclonal antibody can be used in thyroid eye disease
teprotumumab
Why do you get a thyroid storm
What is treatment
Thyroxine potentiates catecholamines –> tachycardia, fever, restlessness, heart failure
Can be triggered by infection, trauma, surgery
TX
-Propythiouracil - used as faster onset and stops peripheral T4 -> T3 conversion
-Propanolol
-Steroids
-Cooling cares
Why do you get a thyroid storm
What is treatment
Thyroxine potentiates catecholamines –> tachycardia, fever, restlessness, heart failure
Can be triggered by infection, trauma, surgery
TX
-Propythiouracil - used as faster onset and stops peripheral T4 -> T3 conversion
-Propanolol
-Steroids
-Cooling cares
in what areas of the nephron do calcitrol and PTH work
Calcitriol works in the proximal convoluted tubule
PTH works in the distal convoluted tubule
what gland makes calcitonin
thyroid gland
how does calcitriol work
inhibits bone resorption
works with GI hormones to inhibit GI absorption of calcium
what affect does PTH have on bone
PTH binds to osteoblasts which triggers them to stop proliferating and express RANK-L. RANK-L binds to the RANK receptor on a pre-osteoblast. This Triggers pre-osteoclast proliferation + maturation -> release acid which breaks down bone causing bone resorption.
Minerals leave the bone
what enzyme in the kidney does PTH upregulate
what does this do
a-1 hydroxylase
Increased conversion of calcidiol to calcitriol
what affect does PTH have on phosphate
stimulates phosphate excretion to prevent hyperphosphataemia as a result of bone resorption
what are the symptoms of hypercalcaemia
bone ache
renal stones
abdomen pain
behavioural changes
what are 2 important causes of secondary hyperparathyroidism
-renal loss - unable to resorb calcium = low serum levels = chronically elevated PTH
-Nutritional deficiency in Vitamin D
What do you see with calcium and phosphate with hypoparathyrodism
low calcium
high phosphate
what is the precursor molecule of cholecalciferol
7-dehydrocholesterol
what occurs in Vitamin D toxicity
Hypercalcaemia
What is rickets
what are the sx
a disease of under mineralised bone at the growth plates
Developmental delay
Easy fractures
-Head: Frontal bossing, delayed fontanelle closure, delayed dentition, softened cranial bones (craniotabes)
-Chest: rachitic rosary, harrisons sulcus
-Limbs: bowing of tibia, valgus or various deformity
what features on investigation would you see in Vitamin D deficiency
Low serum calcium
High PTH
Low serum phosphate
Low calcidiol or calcitriol
What is Vitamin D dependent Rickets Type 1
What is the treatment
defect of a-1-OH
Cannot convert calcidiol -> calcitriol
Calcitriol
What is Vitamin D dependent Rickets Type 2
What is the treatment
Mutation of calcitriol so calcitriol doesn’t work
Need IV calcium infusion OR if partial function very high dose calcitriol
What is the relationship between magnesium and PTH
Hypomagnesium = reduced release of PTH (blunts its response)
HYPOMAGNESIUM CAUSES HYPOCALCAEMIA
PHEX gene defect is seen in what condition
Vitamin D resistant rickets
-PHEX mutation = increased FGF23
-FGF23 inhibits a1-OH resulting in reduced calcitriol
-FGF-23 reduces renal reabsorption of phosphate –> hypophosphataemia
What affect does hypophosphataemia have on calcitriol
calcitriol production is INCREASED secondary to hypophosphataemia
what would be causes for hypocalcaemia + a high PTH
-making PTH but calcium is not being absorbed
-Vitamin D deficiency
-renal loss
-GI malabsorption
-Pseudohypoparathyrodism (tissue resistance to PTH)
What forms of osteogenesis imperfect have blue sclera
What type is fatal
What types have the most severe phenotype
Why do they get hearing loss
Types 1 + 2
Type 2
Types 2 + 3
Otosclerosis
what gives sclera in osteogenesis imperfect the blue appearance
partial visualisation of the choroid
what is the MoA of diaoxide in neonatal hypoglycaemia
Diazoxide opens ATP-dependent potassium channels on pancreatic beta cells in the presence of ATP and Mg2+, resulting in hyperpolarization of the cell and inhibition of insulin release. Diazoxide binds to a different site on the potassium channel than the sulfonylureas.
what do parafollicular cells produce
also known as C-cells
Calcitonin
